[ { "id": "finger-2015-primary", "trial_name": "FINGER", "intervention": "multidomain lifestyle: diet + exercise + cognitive training + vascular risk monitoring, 2 years, vs general health advice control", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "Finnish community-dwelling at-risk older adults (CAIDE Dementia Risk Score >=6, cognition at mean or slightly lower than expected for age), recruited from national surveys", "n_participants": 1260, "age_range": "60-77", "duration": "2 years", "primary_outcome": "change in cognition (comprehensive neuropsychological test battery, NTB total Z score)", "outcome_measure": "NTB total Z score, modified ITT (n=1190)", "result": "positive", "effect_size": "between-group difference in change of NTB total Z score per year 0.022 (95% CI 0.002-0.042); mean 2-year change 0.20 intervention vs 0.16 control", "effect_size_type": "between-group difference in annual change of NTB Z score (standardised composite)", "p_value": "0.030", "cognitive_domain_affected": "global cognition (NTB composite); abstract reports primary composite only", "biomarker_endpoints": "none in primary paper", "year": 2015, "publication": "Ngandu T et al. Lancet 2015;385(9984):2255-63", "url": "https://pubmed.ncbi.nlm.nih.gov/25771249/", "doi": "10.1016/S0140-6736(15)60461-5", "pubmed_id": "25771249", "replication_status": "replicated", "limitations": "Small absolute effect (0.022 Z/year); 2-year duration; control group also improved; adverse events (musculoskeletal pain) 7% vs 1%; single-country proof-of-concept. NCT01041989.", "notes": "MEASURED trial result. Source: PubMed abstract loaded 2026-09-22. Global replications: World-Wide FINGERS network (US POINTER, J-MINT, MIND-CHINA, LatAm-FINGERS, etc.) -- see linked rows." }, { "id": "us-pointer-2025-primary", "trial_name": "US POINTER", "intervention": "structured high-intensity multidomain lifestyle (physical + cognitive activity, MIND-style healthy diet, social engagement, cardiovascular health monitoring; team-based with coaching and accountability) vs self-guided lower-intensity version of the same domains. NOTE: no no-intervention/usual-care control arm.", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social" ], "population": "US older adults at risk of cognitive decline: sedentary lifestyle + suboptimal diet + >=2 of family history of memory impairment, cardiometabolic risk, race/ethnicity, older age, sex; 5 US sites", "n_participants": 2111, "age_range": "60-79", "duration": "2 years", "primary_outcome": "difference between arms in annual rate of change in global cognitive function", "outcome_measure": "global cognitive composite z score (executive function, episodic memory, processing speed); 89% completed year-2 assessment", "result": "mixed", "effect_size": "annual rate of increase 0.243 SD (95% CI 0.227-0.258) structured vs 0.213 SD (95% CI 0.198-0.229) self-guided; between-group difference 0.029 SD/year (95% CI 0.008-0.050)", "effect_size_type": "between-group difference in annual change of global cognitive composite z score (SD units)", "p_value": "0.008", "cognitive_domain_affected": "global composite; benefit consistent for APOE e4 carriers and noncarriers (interaction P=0.95); appeared greater for lower vs higher baseline cognition (interaction P=0.02)", "biomarker_endpoints": "see us-pointer-2026-imaging row: no between-group difference in amyloid, entorhinal tau, hippocampal volume or WMH", "year": 2025, "publication": "Baker LD et al. JAMA 2025;334(8):681-691", "url": "https://pubmed.ncbi.nlm.nih.gov/40720610/", "doi": "10.1001/jama.2025.12923", "pubmed_id": "40720610", "replication_status": "replicated", "limitations": "Both arms improved substantially (0.24 and 0.21 SD/yr, likely practice effects + self-guided arm itself being an intervention); no true control arm so absolute effect of lifestyle change vs nothing cannot be estimated; small between-group difference (0.029 SD/yr); clinical relevance and durability unresolved per authors; single-blind. NCT03688126.", "notes": "Classified 'mixed' because: the prespecified primary comparison was statistically significant (structured > self-guided), but the effect was small, both groups improved, the comparator was an active intervention rather than usual care, and the imaging ancillary study found no effect on AD/vascular brain biomarkers. Serious adverse events 151 structured vs 190 self-guided. Part of World-Wide FINGERS (US adaptation of FINGER). MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "us-pointer-2026-imaging", "trial_name": "US POINTER (Imaging Ancillary)", "intervention": "same as US POINTER: structured vs self-guided multidomain lifestyle intervention; ancillary MRI/PET substudy", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social" ], "population": "US POINTER participants eligible for and consenting to neuroimaging (983 of 1943 assessed; 516 structured, 467 self-guided; 61.5% female; mean age 68.4)", "n_participants": 983, "age_range": "60-79", "duration": "2 years", "primary_outcome": "4 primary imaging outcomes: global beta-amyloid burden (PET), entorhinal cortex tau burden (PET), hippocampal volume, white matter hyperintensity volume", "outcome_measure": "longitudinal PET/MRI change; global cognitive composite", "result": "null", "effect_size": "no intervention-group differences in longitudinal cognitive or imaging outcomes in the imaging subsample; lower baseline hippocampal volume associated with greater cognitive benefit of structured arm (lower HC: 0.077 SD, 95% CI 0.022-0.132; higher HC: 0.002 SD, 95% CI -0.037 to 0.041; interaction P=0.03); ERC tau-cognition association difference 0.289 (95% CI 0.029-0.550; interaction P=0.03)", "effect_size_type": "between-group difference in imaging biomarker trajectories (null); moderation effect sizes in SD units", "p_value": "", "cognitive_domain_affected": "global composite (no group difference in imaging subsample)", "biomarker_endpoints": "amyloid PET: no effect; entorhinal tau PET: no effect; hippocampal volume: no effect; WMH volume: no effect; intervention effects not associated with or moderated by amyloid status", "year": 2026, "publication": "Harrison TM et al. JAMA Neurol 2026;83(6):521-529", "url": "https://pubmed.ncbi.nlm.nih.gov/42008251/", "doi": "10.1001/jamaneurol.2026.0832", "pubmed_id": "42008251", "replication_status": "ongoing", "limitations": "Subsample of parent trial (about half); 2-year window may be too short for biomarker change; no usual-care control.", "notes": "Key for interpreting US POINTER as 'mixed': cognitive signal in parent trial not accompanied by any biomarker change. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "sprint-mind-2019-primary", "trial_name": "SPRINT MIND", "intervention": "intensive antihypertensive treatment to systolic BP goal <120 mm Hg vs standard goal <140 mm Hg", "intervention_components": [ "pharmacologic", "vascular" ], "population": "US/Puerto Rico ambulatory adults >=50 with hypertension and elevated cardiovascular risk, without diabetes or prior stroke; 102 sites", "n_participants": 9361, "age_range": "50+ (mean 67.9)", "duration": "median intervention 3.34 years; median cognitive follow-up 5.11 years", "primary_outcome": "adjudicated probable dementia", "outcome_measure": "incidence of adjudicated probable dementia; secondary: adjudicated MCI, and composite MCI or probable dementia", "result": "mixed", "effect_size": "probable dementia HR 0.83 (95% CI 0.67-1.04), 7.2 vs 8.6 per 1000 person-years (149 vs 176 cases) -- not significant; MCI HR 0.81 (95% CI 0.69-0.95), 14.6 vs 18.3 per 1000 PY; MCI or probable dementia HR 0.85 (95% CI 0.74-0.97), 20.2 vs 24.1 per 1000 PY", "effect_size_type": "hazard ratio", "p_value": "", "cognitive_domain_affected": "clinical diagnosis (MCI / dementia), not domain-specific", "biomarker_endpoints": "secondary MRI analysis (Nasrallah et al. JAMA Neurol 2021, PMID 33683313) -- see separate row if captured", "year": 2019, "publication": "SPRINT MIND Investigators (Williamson JD et al.) JAMA 2019;321(6):553-561", "url": "https://pubmed.ncbi.nlm.nih.gov/30688979/", "doi": "10.1001/jama.2018.21442", "pubmed_id": "30688979", "replication_status": "not-replicated", "limitations": "Primary endpoint (probable dementia) not significant; trial stopped early for CV benefit (Aug 2015) so fewer dementia cases than planned -- authors state likely underpowered for dementia; excluded diabetics and stroke; 91.5% had >=1 follow-up cognitive assessment. NCT01206062.", "notes": "'Mixed': null on primary dementia outcome, significant on secondary MCI and combined outcomes. First large RCT signal that BP lowering reduces MCI. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "mapt-2017-primary", "trial_name": "MAPT", "intervention": "2x2 factorial: multidomain intervention (43 group sessions integrating cognitive training, physical activity, nutrition, plus 3 preventive consultations) and/or omega-3 PUFA (800 mg DHA + 225 mg EPA daily) vs placebo", "intervention_components": [ "cognitive-training", "exercise", "diet", "supplement" ], "population": "community-dwelling non-demented adults >=70 in France and Monaco with spontaneous memory complaint, or limitation in 1 IADL, or slow gait; 13 memory centres", "n_participants": 1680, "age_range": "70+", "duration": "3 years", "primary_outcome": "change from baseline to 36 months in composite cognitive Z score", "outcome_measure": "composite Z score of 4 tests (FCSRT free and total recall, MMSE orientation, Digit Symbol Substitution, Category Naming); modified ITT n=1525", "result": "null", "effect_size": "vs placebo: multidomain + omega-3 0.093 (95% CI 0.001 to 0.184, adjusted p=0.142); multidomain + placebo 0.079 (-0.012 to 0.170, p=0.179); omega-3 alone 0.011 (-0.081 to 0.103, p=0.812)", "effect_size_type": "between-group difference in 3-year change of composite cognitive Z score", "p_value": "0.142 (combined arm, adjusted); 0.179; 0.812", "cognitive_domain_affected": "none significant on primary composite", "biomarker_endpoints": "none in primary paper (amyloid PET substudy exists, not captured here)", "year": 2017, "publication": "Andrieu S et al. Lancet Neurol 2017;16(5):377-389", "url": "https://pubmed.ncbi.nlm.nih.gov/28359749/", "doi": "10.1016/S1474-4422(17)30040-6", "pubmed_id": "28359749", "replication_status": "not-replicated", "limitations": "Multidomain component unblinded; frailer/older population than FINGER; adjusted p-values non-significant despite CI of combined arm excluding zero (multiplicity adjustment). NCT00672685.", "notes": "Major multidomain NULL result -- counterweight to FINGER. Serious adverse events 32-36% across arms, no safety concerns. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "prediva-2016-primary", "trial_name": "preDIVA", "intervention": "6-year nurse-led multidomain cardiovascular risk management (vascular care visits every 4 months) vs usual care; cluster-randomised by general practice", "intervention_components": [ "vascular", "pharmacologic" ], "population": "unselected community-dwelling older adults aged 70-78 from 116 Dutch general practices", "n_participants": 3526, "age_range": "70-78", "duration": "6 years (median follow-up 6.7 years; 21,341 person-years)", "primary_outcome": "cumulative incidence of all-cause dementia and disability (ALDS) at 6 years", "outcome_measure": "incident dementia; Academic Medical Center Linear Disability Score", "result": "null", "effect_size": "dementia 121/1853 (7%) intervention vs 112/1601 (7%) control, HR 0.92 (95% CI 0.71-1.19); disability adjusted mean difference -0.02 (95% CI -0.38 to 0.42); mortality HR 0.98 (0.80-1.18); incident CVD HR 1.06 (0.86-1.31)", "effect_size_type": "hazard ratio (dementia); mean difference (ALDS)", "p_value": "0.54 (dementia); 0.93 (disability)", "cognitive_domain_affected": "none (dementia incidence)", "biomarker_endpoints": "none in primary paper", "year": 2016, "publication": "Moll van Charante EP et al. Lancet 2016;388(10046):797-805", "url": "https://pubmed.ncbi.nlm.nih.gov/27474376/", "doi": "10.1016/S0140-6736(16)30950-3", "pubmed_id": "27474376", "replication_status": "not-replicated", "limitations": "Open-label; unselected population with modest baseline CV risk and high standard of usual care (authors' explanation for null); cluster design. ISRCTN29711771.", "notes": "Major vascular-care NULL result. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "achieve-2023-primary", "trial_name": "ACHIEVE", "intervention": "hearing intervention: audiological counselling + provision and fitting of hearing aids vs health education control (individual sessions with health educator on chronic disease prevention); follow-up every 6 months", "intervention_components": [ "sensory" ], "population": "US adults 70-84 with untreated hearing loss, without substantial cognitive impairment; 4 community sites; two recruitment sources: ARIC cohort (n=238, older, more risk factors, lower baseline cognition) and healthy de novo volunteers (n=739); 88% White", "n_participants": 977, "age_range": "70-84 (mean 76.8)", "duration": "3 years", "primary_outcome": "3-year change in global cognition standardised factor score from comprehensive neurocognitive battery", "outcome_measure": "global cognition factor score (SD units), ITT", "result": "mixed", "effect_size": "total cohort: 3-year change -0.200 (95% CI -0.256 to -0.144) hearing vs -0.202 (-0.258 to -0.145) control; difference 0.002 (95% CI -0.077 to 0.081), p=0.96 [NULL]. Prespecified sensitivity analysis by cohort (p interaction=0.010): ARIC cohort difference 0.191 (95% CI 0.022 to 0.360), p=0.027, described as a 48% reduction in 3-year cognitive change; de novo cohort difference -0.061 (95% CI -0.151 to 0.028), p=0.18", "effect_size_type": "between-group difference in 3-year change of global cognition factor score (SD units); relative reduction in cognitive change (ARIC subgroup)", "p_value": "0.96 (primary); 0.010 (cohort interaction); 0.027 (ARIC subgroup)", "cognitive_domain_affected": "global cognition composite; no significant effect in total cohort", "biomarker_endpoints": "none in primary paper", "year": 2023, "publication": "Lin FR et al. Lancet 2023;402(10404):786-797", "url": "https://pubmed.ncbi.nlm.nih.gov/37478886/", "doi": "10.1016/S0140-6736(23)01406-X", "pubmed_id": "37478886", "replication_status": "not-replicated", "limitations": "Primary analysis null; the widely cited 48% figure is a prespecified sensitivity/subgroup analysis in the higher-risk ARIC cohort (24% of sample) and needs replication; unmasked; 88% White; healthy-volunteer de novo cohort declined less than expected. NCT03243422.", "notes": "Primary null + positive prespecified subgroup = 'mixed'. Subgroup figures taken from PMC full text (PMC10529382), primary figures from abstract. MEASURED. Loaded 2026-09-22." }, { "id": "evoke-evokeplus-2026-primary", "trial_name": "evoke / evoke+", "intervention": "oral semaglutide (GLP-1 receptor agonist) up to 14 mg once daily (flexible dose) vs placebo for up to 156 weeks", "intervention_components": [ "pharmacologic" ], "population": "amyloid-confirmed early symptomatic Alzheimer's disease (MCI or mild dementia due to AD), aged 55-85; evoke+ additionally allowed significant small-vessel pathology (54 participants, 2.8%); 566 sites in 40 countries", "n_participants": 3808, "age_range": "55-85 (mean 72.2)", "duration": "104 weeks primary endpoint (treatment up to 156 weeks); trials discontinued for negative outcome", "primary_outcome": "change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) from baseline to week 104", "outcome_measure": "CDR-SB (all randomised participants)", "result": "null", "effect_size": "evoke: CDR-SB change 2.3 (SE 0.1) semaglutide vs 2.3 (0.1) placebo, estimated difference -0.08 (95% CI -0.35 to 0.20); evoke+: 2.2 vs 2.1, difference 0.10 (95% CI -0.17 to 0.38)", "effect_size_type": "between-group difference in CDR-SB change at week 104", "p_value": "0.57 (evoke); 0.46 (evoke+)", "cognitive_domain_affected": "none (global clinical progression unchanged)", "biomarker_endpoints": "amyloid-confirmed enrolment; biomarker secondary outcomes not reported in abstract", "year": 2026, "publication": "Lancet 2026;407(10544):2167-2179 (evoke and evoke+ investigators)", "url": "https://pubmed.ncbi.nlm.nih.gov/41865758/", "doi": "10.1016/S0140-6736(26)00459-9", "pubmed_id": "41865758", "replication_status": "not-replicated", "limitations": "Treatment trial in symptomatic AD, not a primary-prevention trial; observational GLP-1/dementia associations were not confirmed; TEAEs 91.2% semaglutide vs 84.8% placebo. NCT04777396, NCT04777409. Both trials discontinued.", "notes": "Definitive NULL for semaglutide in early AD (evoke n=1855: 928 vs 927; evoke+ n=1953: 976 vs 977). Novo Nordisk sponsor. Included because GLP-1 prevention interest was heavily driven by these trials. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "jmint-2024-primary", "trial_name": "J-MINT", "intervention": "18-month multidomain intervention: management of vascular risk factors + exercise + nutritional counselling + cognitive training vs control", "intervention_components": [ "vascular", "exercise", "diet", "cognitive-training" ], "population": "Japanese community-dwelling older adults 65-85 with mild cognitive impairment", "n_participants": 531, "age_range": "65-85", "duration": "18 months", "primary_outcome": "change in cognitive composite score over 18 months", "outcome_measure": "cognitive composite score; 406 completed", "result": "null", "effect_size": "between-group difference in composite change 0.047 (95% CI -0.029 to 0.124)", "effect_size_type": "between-group difference in change of composite cognitive score", "p_value": "", "cognitive_domain_affected": "none significant on primary composite; secondary health outcomes positive; exploratory benefit in high exercise-attendance, APOE e4 carriers, and elevated plasma GFAP subgroups", "biomarker_endpoints": "plasma GFAP used as effect-modifier (exploratory), not an outcome in abstract", "year": 2024, "publication": "Sakurai T et al. Alzheimers Dement 2024;20(6):3918-3930", "url": "https://pubmed.ncbi.nlm.nih.gov/38646854/", "doi": "10.1002/alz.13838", "pubmed_id": "38646854", "replication_status": "not-replicated", "limitations": "MCI population (later stage than FINGER); 18 months; 24% attrition; subgroup findings exploratory.", "notes": "World-Wide FINGERS member trial; NULL on primary. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "latam-fingers-2026-primary", "trial_name": "LatAm-FINGERS", "intervention": "2-year culturally adapted systematic multidomain lifestyle intervention (SLI: structured, supervised, monitored) vs flexible lifestyle intervention (FLI: health advice)", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social" ], "population": "at-risk adults 60-77 (CAIDE score >=6 and suboptimal cognitive performance) in 11 Latin American countries; 75% women; 59% Mestizo, 27% White", "n_participants": 1065, "age_range": "60-77 (mean 67.5)", "duration": "2 years", "primary_outcome": "co-primary: feasibility (RE-AIM Reach/Implementation/Maintenance) and change in global cognitive composite over 2 years", "outcome_measure": "global cognitive composite z score; 82.3% completed 2-year follow-up", "result": "positive", "effect_size": "mean annual change 0.31 SD (95% CI 0.28-0.34) SLI vs 0.20 SD (0.17-0.23) FLI; between-group difference 0.11 SD per year (95% CI 0.06-0.15)", "effect_size_type": "between-group difference in annual change of global cognitive composite (SD units)", "p_value": "<0.0001", "cognitive_domain_affected": "global cognitive composite", "biomarker_endpoints": "none in primary paper", "year": 2026, "publication": "Lancet 2026;408(10553):417-429", "url": "https://pubmed.ncbi.nlm.nih.gov/42442374/", "doi": "10.1016/S0140-6736(26)01278-X", "pubmed_id": "42442374", "replication_status": "replicated", "limitations": "Comparator was an active health-advice arm, not usual care; both groups improved (practice effects likely); participants and staff unmasked; analytic sample 1065 of 1719 assessed; higher dropout in FLI (20.2% vs 15.2%); adverse events far more frequent in SLI (412 vs 66, mostly musculoskeletal). NCT06492967.", "notes": "Largest FINGER-model effect reported to date (0.11 SD/yr, vs 0.029 in US POINTER and 0.022 in FINGER). Feasibility co-primary: Reach 62.0%, adherence 71.6%. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "elad-liraglutide-2026-primary", "trial_name": "ELAD", "intervention": "daily subcutaneous liraglutide (GLP-1 receptor agonist) vs placebo for 52 weeks", "intervention_components": [ "pharmacologic" ], "population": "mild to moderate Alzheimer's disease syndrome, non-diabetic; multicentre UK phase 2b", "n_participants": 204, "age_range": "", "duration": "52 weeks", "primary_outcome": "change in cerebral glucose metabolic rate (FDG-PET)", "outcome_measure": "FDG-PET cerebral glucose metabolism; secondary: ADAS-Exec, ADCS-ADL, CDR-SB, MRI", "result": "null", "effect_size": "primary FDG-PET difference -0.17 (95% CI -0.39 to 0.06), P=0.14; ADAS-Exec better with liraglutide 0.15 (95% CI 0.03-0.28), unadjusted P=0.01; ADCS-ADL -0.58 (95% CI -3.13 to 1.97), P=0.65; CDR-SB -0.06 (95% CI -0.57 to 0.44), P=0.81", "effect_size_type": "between-group difference (units per outcome scale)", "p_value": "0.14 (primary)", "cognitive_domain_affected": "executive function (secondary, unadjusted P=0.01 only); no effect on global clinical measures", "biomarker_endpoints": "FDG-PET glucose metabolism: no significant effect (primary); MRI collected", "year": 2026, "publication": "Edison P et al. Nat Med 2026;32(1):353-361 (epub Dec 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41326666/", "doi": "10.1038/s41591-025-04106-7", "pubmed_id": "41326666", "replication_status": "not-replicated", "limitations": "Phase 2b, small n, symptomatic AD (treatment, not prevention); secondary cognitive signal unadjusted for multiplicity. NCT01843075.", "notes": "GLP-1 context row. Null on primary; exploratory executive-function signal. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "jmint-2025-vrf-secondary", "trial_name": "J-MINT (secondary: vascular risk factor moderation)", "intervention": "same as J-MINT 18-month multidomain intervention; secondary analysis by presence of untreated/uncontrolled vascular risk factors (BP, HbA1c, HDL, non-HDL cholesterol)", "intervention_components": [ "vascular", "exercise", "diet", "cognitive-training" ], "population": "J-MINT participants (MCI, 65-85); 298 had >=1 untreated or uncontrolled VRF", "n_participants": 531, "age_range": "65-85", "duration": "18 months", "primary_outcome": "interaction of intervention x VRF status on change in average neuropsychological Z score over 18 months", "outcome_measure": "average Z score of neuropsychological tests, mixed-effects model", "result": "positive", "effect_size": "in participants with VRFs: Z score difference 0.11 (95% CI 0.02-0.20); no benefit in those without VRFs; interaction p=0.032", "effect_size_type": "between-group difference in cognitive Z score change (subgroup)", "p_value": "0.032 (interaction)", "cognitive_domain_affected": "global (average Z score)", "biomarker_endpoints": "secondary improvements in systolic BP, pulse pressure, HDL, triglycerides reported", "year": 2025, "publication": "Alzheimers Dement 2025 (J-MINT investigators)", "url": "https://pubmed.ncbi.nlm.nih.gov/41222037/", "doi": "10.1002/alz.70822", "pubmed_id": "41222037", "replication_status": "not-replicated", "limitations": "Secondary/subgroup analysis of a trial that was null on its primary outcome; hypothesis-generating. UMIN000038671.", "notes": "Supports the 'target higher-risk populations' hypothesis seen also in ACHIEVE (ARIC cohort) and US POINTER (lower baseline cognition). MEASURED. Loaded 2026-09-22." }, { "id": "smarrt-2023-primary", "trial_name": "SMARRT", "intervention": "2-year personalised multidomain risk-reduction: participant-chosen goals across 8 targeted risk factors with health coaching and nurse visits vs health education control; shifted to remote delivery during COVID-19", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social", "sensory" ], "population": "adults 70-89 at elevated dementia risk (>=2 of 8 targeted risk factors) from Kaiser Permanente Washington primary care; 62.8% women; mean age 75.7", "n_participants": 172, "age_range": "70-89", "duration": "2 years", "primary_outcome": "change in composite modified Neuropsychological Test Battery", "outcome_measure": "composite mNTB score (SD units), average treatment effect via linear mixed models, ITT", "result": "positive", "effect_size": "composite cognition ATE 0.14 SD (95% CI 0.03-0.25), described as 74% improvement vs control change; composite risk-factor score ATE 0.11 SD (95% CI 0.01-0.20, P=0.03); QOL ATE 0.81 points (95% CI -0.21 to 1.84, P=0.12)", "effect_size_type": "average treatment effect in SD units", "p_value": "0.02", "cognitive_domain_affected": "global composite", "biomarker_endpoints": "none", "year": 2024, "publication": "Yaffe K et al. JAMA Intern Med 2024;184(1):54-62 (online Nov 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/38010725/", "doi": "10.1001/jamainternmed.2023.6279", "pubmed_id": "38010725", "replication_status": "not-replicated", "limitations": "Small pilot-scale trial (n=172); COVID-19 forced switch to remote delivery; musculoskeletal pain 14 vs 0. NCT03683394.", "notes": "Personalised (not one-size) multidomain design. Musculoskeletal adverse events recur across multidomain trials (FINGER, LatAm-FINGERS, SMARRT). MEASURED. Loaded 2026-09-22." }, { "id": "mind-diet-trial-2023-primary", "trial_name": "MIND Diet Trial", "intervention": "MIND diet (Mediterranean-DASH hybrid) with mild caloric restriction vs control diet with mild caloric restriction; both arms received dietary counselling and weight-loss support; 3 years", "intervention_components": [ "diet" ], "population": "cognitively unimpaired older adults with family history of dementia, BMI >25 and suboptimal diet; two US sites (Chicago, Boston)", "n_participants": 604, "age_range": "65+", "duration": "3 years", "primary_outcome": "change from baseline in global cognition score and four domain scores (12-test battery)", "outcome_measure": "global cognition z score; 93.4% completed", "result": "null", "effect_size": "global cognition improved in both groups: +0.205 SD MIND vs +0.170 SD control; mean difference 0.035 SD (95% CI -0.022 to 0.092)", "effect_size_type": "between-group difference in 3-year change of global cognition z score", "p_value": "0.23", "cognitive_domain_affected": "none", "biomarker_endpoints": "MRI (non-random subsample): white-matter hyperintensities, hippocampal volume, total grey/white matter volumes -- no difference between groups", "year": 2023, "publication": "Barnes LL et al. N Engl J Med 2023;389(7):602-611", "url": "https://pubmed.ncbi.nlm.nih.gov/37466280/", "doi": "10.1056/NEJMoa2302368", "pubmed_id": "37466280", "replication_status": "not-replicated", "limitations": "Control diet also involved counselling and caloric restriction (active comparator); both groups improved (practice effects/weight loss); age range not stated in abstract (65+ per trial design, from PMC). NCT02817074.", "notes": "Key single-domain diet NULL despite strong observational MIND-diet associations. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "cpap-osa-rct-2025", "trial_name": "CPAP in OSA (multicentre China RCT, NCT02886156)", "intervention": "12 months of continuous positive airway pressure (CPAP) plus best supportive care vs best supportive care alone", "intervention_components": [ "sensory" ], "population": "middle-aged adults with obstructive sleep apnea (AHI >=15/h) and normal cognition; 5 hospitals, China, 2017-2021", "n_participants": 148, "age_range": "middle-aged (not specified in abstract)", "duration": "12 months (primary endpoint at 6 months)", "primary_outcome": "Montreal Cognitive Assessment (MoCA) score at 6 months", "outcome_measure": "MoCA; secondary: default-mode-network functional connectivity, cortical thickness (MRI)", "result": "mixed", "effect_size": "MoCA difference -0.04 (95% CI -0.72 to 0.65), P=0.91 [null]; DMN functional connectivity difference -13.73 (95% CI -23.40 to -4.06), P=0.01; cortical thickness difference -0.06 mm (95% CI -0.10 to -0.01), P=0.02", "effect_size_type": "between-group difference (MoCA points; imaging units)", "p_value": "0.91 (primary)", "cognitive_domain_affected": "none on MoCA", "biomarker_endpoints": "MRI: cortical thickness and DMN connectivity differed between groups (authors interpret as recovery from atrophic processes)", "year": 2025, "publication": "Am J Respir Crit Care Med 2025;211(4):628-636", "url": "https://pubmed.ncbi.nlm.nih.gov/39998447/", "doi": "10.1164/rccm.202406-1170OC", "pubmed_id": "39998447", "replication_status": "not-replicated", "limitations": "Small; cognitively normal participants with ceiling on MoCA; short; not an older/at-risk-for-dementia population; 'sensory' tag used as closest schema category for a sleep/breathing intervention.", "notes": "Sleep-intervention row. Cognitive primary NULL; imaging secondary positive. MEASURED. Loaded 2026-09-22." }, { "id": "cbti-amyloid-rct-2026", "trial_name": "CBT-I in older adults with insomnia (NCT03954210)", "intervention": "cognitive behavioural therapy for insomnia (CBT-I) vs control; assessments at baseline, 6 weeks and 1 year", "intervention_components": [ "cognitive-training" ], "population": "cognitively normal older adults with insomnia symptoms", "n_participants": 200, "age_range": "older adults (not specified in abstract)", "duration": "1 year", "primary_outcome": "change in cognitive performance (processing speed, executive function, memory) and amyloid-beta burden (subsample n=50)", "outcome_measure": "domain cognitive scores; amyloid PET (subsample)", "result": "null", "effect_size": "processing speed mean difference 0.017 (95% CI -0.1036 to 0.1376), p=0.78; executive function -0.0881 (95% CI -0.2945 to 0.1182), p=0.40; memory 0.4068 (95% CI -2.3965 to 3.2101), p=0.77; no group difference in amyloid deposition", "effect_size_type": "between-group difference in change (test units)", "p_value": "0.78; 0.40; 0.77", "cognitive_domain_affected": "none", "biomarker_endpoints": "amyloid-beta deposition (n=50 subsample): no difference", "year": 2026, "publication": "Alzheimers Dement 2026;22(6):e71591", "url": "https://pubmed.ncbi.nlm.nih.gov/42298279/", "doi": "10.1002/alz.71591", "pubmed_id": "42298279", "replication_status": "not-replicated", "limitations": "1-year follow-up too short for AD-risk outcomes per authors; small amyloid subsample; 'cognitive-training' tag used for a behavioural (CBT) intervention as closest schema category.", "notes": "Sleep-intervention row (behavioural). NULL. MEASURED. Loaded 2026-09-22." }, { "id": "suvorexant-csf-2023", "trial_name": "Suvorexant acute CSF study (Lucey et al.)", "intervention": "single dose suvorexant 10 mg or 20 mg (dual orexin receptor antagonist, insomnia drug) vs placebo with serial CSF sampling over 36 hours", "intervention_components": [ "pharmacologic" ], "population": "cognitively unimpaired adults 45-65", "n_participants": 38, "age_range": "45-65", "duration": "36 hours (acute)", "primary_outcome": "CSF amyloid-beta, tau and phospho-tau concentrations (mass spectrometry)", "outcome_measure": "CSF p-tau181/tau181 ratio; CSF amyloid-beta", "result": "positive", "effect_size": "p-tau181 phosphorylation ratio decreased ~10-15% with suvorexant 20 mg vs placebo; amyloid-beta decreased ~10-20% vs placebo from 5 h after dosing; no decrease at tau-S202 or tau-T217", "effect_size_type": "percent change in CSF biomarker vs placebo", "p_value": "", "cognitive_domain_affected": "none measured (biomarker-only)", "biomarker_endpoints": "CSF amyloid-beta down ~10-20%; CSF p-tau181 ratio down ~10-15% (20 mg); p-tau202 and p-tau217 unchanged", "year": 2023, "publication": "Lucey BP et al. Ann Neurol 2023;94(1):27-40", "url": "https://pubmed.ncbi.nlm.nih.gov/36897120/", "doi": "10.1002/ana.26641", "pubmed_id": "36897120", "replication_status": "not-replicated", "limitations": "Tiny acute mechanistic study; no cognitive or clinical outcome; chronic-treatment trials needed per authors.", "notes": "Sleep-pharmacology biomarker row; mechanistic support only, NOT evidence of prevention. MEASURED. Loaded 2026-09-22." }, { "id": "active-20yr-claims-dementia-2026", "trial_name": "ACTIVE (20-year Medicare-claims follow-up)", "intervention": "four-arm cognitive training RCT: memory training, reasoning training, speed-of-processing training (with optional booster sessions), or no-contact control; linked to Medicare claims 1999-2019", "intervention_components": [ "cognitive-training" ], "population": "ACTIVE participants enrolled in traditional Medicare at baseline (older adults 65+, diverse US sample)", "n_participants": 2021, "age_range": "65+", "duration": "20 years follow-up", "primary_outcome": "claims-based diagnosed Alzheimer's disease and related dementias (Chronic Conditions Warehouse algorithm)", "outcome_measure": "hazard of ADRD diagnosis", "result": "mixed", "effect_size": "speed training with >=1 booster session HR 0.75 (95% CI 0.59-0.95); speed training without booster HR 1.01 (95% CI 0.81-1.27); no main effect of memory or reasoning training", "effect_size_type": "hazard ratio", "p_value": "", "cognitive_domain_affected": "processing speed training arm only", "biomarker_endpoints": "none", "year": 2026, "publication": "Alzheimers Dement (N Y) 2026;12(1):e70197", "url": "https://pubmed.ncbi.nlm.nih.gov/41669119/", "doi": "10.1002/trc2.70197", "pubmed_id": "41669119", "replication_status": "not-replicated", "limitations": "Claims-based (not adjudicated) dementia; booster completion is post-randomisation (self-selected), so the HR 0.75 is not a pure ITT effect; original ACTIVE trial had no primary dementia outcome; sample restricted to traditional Medicare enrolees.", "notes": "Effect is confined to a post-randomisation subgroup; ITT main effect of speed training alone not significant. MEASURED (claims). Loaded 2026-09-22." }, { "id": "exert-2025-primary", "trial_name": "EXERT", "intervention": "18 months of supervised (first 12 months) moderate-high intensity aerobic training vs low-intensity stretching/balance/range-of-motion", "intervention_components": [ "exercise" ], "population": "sedentary older adults with amnestic MCI; multicentre US phase 3", "n_participants": 296, "age_range": "65-89 (per trial design; abstract states older adults)", "duration": "18 months", "primary_outcome": "global cognitive composite (ADAS-Cog-Exec) at 12 months", "outcome_measure": "ADAS-Cog-Exec; hippocampal volume", "result": "null", "effect_size": "aerobic vs stretching regression coefficient -0.078 (SE 0.074); no 12-month cognitive decline in either group; mean 12-month hippocampal volume loss 0.51% in both groups", "effect_size_type": "regression coefficient (between-group difference in cognitive trajectory)", "p_value": "0.3", "cognitive_domain_affected": "none (no difference by exercise intensity)", "biomarker_endpoints": "hippocampal volume loss 0.51% over 12 months (both arms, described as low)", "year": 2025, "publication": "Baker LD et al. Alzheimers Dement 2025;21(4):e14586", "url": "https://pubmed.ncbi.nlm.nih.gov/40271888/", "doi": "10.1002/alz.14586", "pubmed_id": "40271888", "replication_status": "not-replicated", "limitations": "No no-exercise control (both arms exercised, so absolute exercise effect unmeasured); the companion ADNI comparison (PMID 40271887) is non-randomised; age range stated from trial design rather than abstract.", "notes": "Exercise-intensity NULL; stability in both arms vs ADNI natural history is observational. MEASURED. Loaded 2026-09-22." }, { "id": "preadvise-2017-primary", "trial_name": "PREADViSE", "intervention": "vitamin E, selenium, both, or placebo (ancillary to SELECT prostate-cancer trial); RCT 2002-2009 then cohort follow-up 2009-2015", "intervention_components": [ "supplement" ], "population": "asymptomatic men >=60 at 130 SELECT sites; 10.0% Black, 6.7% Hispanic; 3786 continued into cohort phase", "n_participants": 7540, "age_range": "60+ (mean 67.5)", "duration": "up to 13 years (RCT phase to 2009, cohort to 2015)", "primary_outcome": "incident dementia", "outcome_measure": "consensus-adjudicated dementia via 2-stage cognitive screen and records", "result": "null", "effect_size": "dementia incidence 325/7338 (4.4%) not different among arms; adjusted HR vs placebo: vitamin E 0.88 (95% CI 0.64-1.20), selenium 0.83 (0.60-1.13), combination 1.00 (0.75-1.35)", "effect_size_type": "hazard ratio", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2017, "publication": "Kryscio RJ et al. JAMA Neurol 2017;74(5):567-573", "url": "https://pubmed.ncbi.nlm.nih.gov/28319243/", "doi": "10.1001/jamaneurol.2016.5778", "pubmed_id": "28319243", "replication_status": "not-replicated", "limitations": "Trial terminated early (SELECT futility 2009) and converted to cohort; low dementia incidence; men only; telephone screening in cohort phase.", "notes": "Supplement NULL. MEASURED. Loaded 2026-09-22." }, { "id": "gem-ginkgo-2008-primary", "trial_name": "GEM (Ginkgo Evaluation of Memory)", "intervention": "Ginkgo biloba extract 120 mg twice daily vs placebo", "intervention_components": [ "supplement" ], "population": "community volunteers >=75 with normal cognition (n=2587) or MCI (n=482); 5 US academic centres; 2000-2008", "n_participants": 3069, "age_range": "75+", "duration": "median 6.1 years", "primary_outcome": "incident all-cause dementia and Alzheimer disease (expert-panel consensus)", "outcome_measure": "incident dementia; 523 cases", "result": "null", "effect_size": "all-cause dementia HR 1.12 (95% CI 0.94-1.33), P=0.21 (3.3 vs 2.9 per 100 person-years); AD HR 1.16 (95% CI 0.97-1.39), P=0.11; MCI-to-dementia HR 1.13 (95% CI 0.85-1.50), P=0.39", "effect_size_type": "hazard ratio", "p_value": "0.21 (all-cause dementia)", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2008, "publication": "DeKosky ST et al. JAMA 2008;300(19):2253-62", "url": "https://pubmed.ncbi.nlm.nih.gov/19017911/", "doi": "10.1001/jama.2008.683", "pubmed_id": "19017911", "replication_status": "not-replicated", "limitations": "Point estimate numerically favours placebo (non-significant); dropout 6.3%. NCT00010803.", "notes": "Largest supplement-based dementia prevention RCT; NULL. MEASURED. Loaded 2026-09-22." }, { "id": "look-ahead-cognition-2017", "trial_name": "Look AHEAD (cognitive outcomes)", "intervention": "intensive lifestyle intervention for weight loss and physical activity (average 10 years) vs diabetes support and education", "intervention_components": [ "diet", "exercise" ], "population": "overweight/obese adults with type 2 diabetes (US multicentre); cognitive assessment in 3802 randomised participants at mean 11.4 years (mean age 69.6 at assessment)", "n_participants": 3802, "age_range": "54.9-87.2 at assessment (45-76 at enrolment per trial design)", "duration": "average 11.4 years after enrolment", "primary_outcome": "prevalence of centrally adjudicated MCI and probable dementia", "outcome_measure": "standardised cognitive battery with proxy functional interview when below threshold", "result": "null", "effect_size": "MCI prevalence 6.4% intervention vs 6.6% control; probable dementia 1.8% vs 1.8%; p=0.93; interaction with baseline BMI p=0.03 (effect ranged from benefit at low BMI to harm at high BMI)", "effect_size_type": "prevalence difference", "p_value": "0.93", "cognitive_domain_affected": "none", "biomarker_endpoints": "none in this paper", "year": 2017, "publication": "Espeland MA et al. Neurology 2017;88(21):2026-2035", "url": "https://pubmed.ncbi.nlm.nih.gov/28446656/", "doi": "10.1212/WNL.0000000000003955", "pubmed_id": "28446656", "replication_status": "not-replicated", "limitations": "Cognition was not a primary trial outcome; single cross-sectional assessment (prevalence, not incidence); Class II evidence. NCT00017953.", "notes": "Weight-loss/exercise lifestyle NULL in diabetes; possible harm signal at highest BMI. MEASURED. Loaded 2026-09-22." }, { "id": "life-2015-cognition", "trial_name": "LIFE (cognitive outcomes)", "intervention": "24-month structured moderate-intensity physical activity programme (walking, resistance, flexibility) vs health education workshops + upper-extremity stretching", "intervention_components": [ "exercise" ], "population": "sedentary community-living adults 70-89 at risk for mobility disability but able to walk 400 m; 8 US centres", "n_participants": 1635, "age_range": "70-89", "duration": "24 months", "primary_outcome": "prespecified secondary outcomes: Digit Symbol Coding and HVLT-R delayed recall; tertiary: global/executive composites, incident MCI or dementia", "outcome_measure": "DSC (0-133), HVLT-R; assessed in 1476 (90.3%)", "result": "null", "effect_size": "DSC 46.26 vs 46.28, mean difference -0.01 (95% CI -0.80 to 0.77), P=0.97; HVLT-R delayed recall 7.22 vs 7.25, difference -0.03 words (95% CI -0.29 to 0.24), P=0.84; incident MCI/dementia 13.2% vs 12.1%, OR 1.08 (95% CI 0.80-1.46); executive-function benefit in >=80 y and poorer baseline physical performance subgroups (interaction P=0.01)", "effect_size_type": "adjusted mean difference (test points); odds ratio", "p_value": "0.97; 0.84", "cognitive_domain_affected": "none overall; executive function in >=80 and low-function subgroups", "biomarker_endpoints": "none", "year": 2015, "publication": "Sink KM et al. JAMA 2015;314(8):781-90", "url": "https://pubmed.ncbi.nlm.nih.gov/26305648/", "doi": "10.1001/jama.2015.9617", "pubmed_id": "26305648", "replication_status": "not-replicated", "limitations": "Cognition was a secondary outcome; active control; frail/mobility-limited population. NCT01072500.", "notes": "Largest exercise-only RCT with cognitive outcomes; NULL. MEASURED. Loaded 2026-09-22." }, { "id": "cosmos-mind-2023-cognition", "trial_name": "COSMOS-Mind", "intervention": "2x2 factorial: cocoa extract (500 mg/day flavanols) vs placebo and daily multivitamin-mineral (Centrum Silver) vs placebo, 3 years; telephone cognitive assessment", "intervention_components": [ "supplement" ], "population": "US older adults (mean age 73; 60% women; 89% non-Hispanic White); ancillary to COSMOS", "n_participants": 2262, "age_range": "65+ (women), 60+ (men) per COSMOS design; mean 73", "duration": "3 years", "primary_outcome": "change in global cognition composite with cocoa extract (primary); with multivitamin (prespecified secondary)", "outcome_measure": "global cognition z composite from telephone battery (TICS, word list, story recall, oral trails, fluency, number span, digit ordering); 92% completed baseline + >=1 annual", "result": "mixed", "effect_size": "cocoa extract: mean z 0.03 (95% CI -0.02 to 0.08), P=0.28 [null]; multivitamin: mean z 0.07 (95% CI 0.02-0.12), P=0.007 [positive]; multivitamin effect with CVD history 0.14 (95% CI -0.02 to 0.31) vs no history 0.06 (0.01-0.11), interaction nominal P=0.01", "effect_size_type": "between-group difference in global cognition z score", "p_value": "0.28 (cocoa); 0.007 (multivitamin)", "cognitive_domain_affected": "global, memory and executive function (multivitamin); none (cocoa)", "biomarker_endpoints": "none", "year": 2023, "publication": "Baker LD et al. Alzheimers Dement 2023;19(4):1308-1319", "url": "https://pubmed.ncbi.nlm.nih.gov/36102337/", "doi": "10.1002/alz.12767", "pubmed_id": "36102337", "replication_status": "replicated", "limitations": "Multivitamin was the secondary comparison; telephone-only testing; 89% non-Hispanic White; incident MCI/dementia not reduced (see cosmos-mind-2023-incidence row).", "notes": "'Mixed': cocoa null, multivitamin positive on cognition. The multivitamin effect was subsequently reported in COSMOS-Web and COSMOS-Clinic (not captured here). MEASURED. Loaded 2026-09-22." }, { "id": "cosmos-mind-2023-incidence", "trial_name": "COSMOS-Mind (incident MCI/dementia)", "intervention": "same 2x2 factorial: cocoa extract and multivitamin-mineral vs placebo, 3 years", "intervention_components": [ "supplement" ], "population": "COSMOS-Mind participants", "n_participants": 2262, "age_range": "mean 73", "duration": "3 years", "primary_outcome": "incident adjudicated MCI and all-cause probable dementia", "outcome_measure": "proportional hazards; 110 incident MCI, 14 incident dementia", "result": "null", "effect_size": "incidence rates did not vary by multivitamin or cocoa assignment (all p >= 0.05); among converters to MCI, multivitamin group had higher global cognition (p=0.03) and executive function (p<0.001) scores", "effect_size_type": "hazard comparison (values not in abstract)", "p_value": ">=0.05", "cognitive_domain_affected": "none for incidence", "biomarker_endpoints": "none", "year": 2023, "publication": "Alzheimers Dement 2023;19(11):4863-4871", "url": "https://pubmed.ncbi.nlm.nih.gov/37035889/", "doi": "10.1002/alz.13078", "pubmed_id": "37035889", "replication_status": "not-replicated", "limitations": "Very low event counts (14 dementia); authors state low statistical power.", "notes": "Companion NULL for clinical incidence endpoints despite cognitive-score benefit. MEASURED. Loaded 2026-09-22." }, { "id": "aspree-aspirin-2020", "trial_name": "ASPREE (dementia and cognition)", "intervention": "low-dose aspirin 100 mg daily vs placebo", "intervention_components": [ "pharmacologic" ], "population": "community-dwelling adults >=70 (US minorities >=65) in US and Australia, free of CVD, disability and dementia", "n_participants": 19114, "age_range": "70+ (US minorities 65+)", "duration": "median 4.7 years", "primary_outcome": "incident all-cause dementia (DSM-IV adjudicated), probable AD, MCI, cognitive decline", "outcome_measure": "575 adjudicated dementia cases; 3MS, HVLT-R, SDMT, COWAT", "result": "null", "effect_size": "dementia triggers HR 1.03 (95% CI 0.91-1.17); probable AD HR 0.96 (95% CI 0.74-1.24); MCI HR 1.12 (95% CI 0.92-1.37); cognitive change similar", "effect_size_type": "hazard ratio", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2020, "publication": "Ryan J et al. Neurology 2020;95(3):e320-e331", "url": "https://pubmed.ncbi.nlm.nih.gov/32213642/", "doi": "10.1212/WNL.0000000000009277", "pubmed_id": "32213642", "replication_status": "not-replicated", "limitations": "Class II evidence; follow-up ongoing at publication. NCT01038583.", "notes": "Largest pharmacologic prevention NULL. MEASURED. Loaded 2026-09-22." }, { "id": "crhcp-2025-dementia", "trial_name": "CRHCP (China Rural Hypertension Control Project) dementia outcome", "intervention": "non-physician community healthcare provider-led stepped-care antihypertensive titration to systolic <130 / diastolic <80 mm Hg (with physician supervision, home BP monitoring, health coaching) vs usual care; village-level cluster randomisation", "intervention_components": [ "pharmacologic", "vascular" ], "population": "adults >=40 with uncontrolled hypertension in 326 rural Chinese villages (163 intervention, 163 usual care)", "n_participants": 33995, "age_range": "40+", "duration": "48 months", "primary_outcome": "all-cause dementia (blinded endpoint adjudication)", "outcome_measure": "risk ratio for all-cause dementia over 48 months", "result": "positive", "effect_size": "all-cause dementia RR 0.85 (95% CI 0.76-0.95); net SBP reduction 22.0 mm Hg (95% CI 20.6-23.4), DBP reduction 9.3 mm Hg (95% CI 8.7-10.0); serious adverse events RR 0.94 (95% CI 0.91-0.98)", "effect_size_type": "risk ratio", "p_value": "0.0035", "cognitive_domain_affected": "clinical dementia diagnosis", "biomarker_endpoints": "none", "year": 2025, "publication": "He J et al. Nat Med 2025;31(6):2054-2061", "url": "https://pubmed.ncbi.nlm.nih.gov/40258956/", "doi": "10.1038/s41591-025-03616-8", "pubmed_id": "40258956", "replication_status": "not-replicated", "limitations": "Open-label cluster design; rural China with very large achievable BP reduction (22 mm Hg) and low baseline treatment, so generalisability to well-treated populations is uncertain; only a 4-year window. NCT03527719.", "notes": "First large RCT with all-cause dementia as PRIMARY outcome to show significant reduction from BP lowering. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "sprint-mind-2025-extended", "trial_name": "SPRINT MIND (extended follow-up)", "intervention": "intensive (SBP <120) vs standard (SBP <140) treatment for 3.3 years; cognitive status re-ascertained by telephone from Dec 2019", "intervention_components": [ "pharmacologic", "vascular" ], "population": "SPRINT participants; 7221 (77%) eligible for recontact, cognitive status ascertained for 4232 (59%); mean age 67, 36% female", "n_participants": 9361, "age_range": "50+", "duration": "median 7 years follow-up", "primary_outcome": "probable dementia (prespecified secondary analysis with extended follow-up)", "outcome_measure": "adjudicated probable dementia, MCI, composite; 216 new cases accrued vs 326 targeted", "result": "mixed", "effect_size": "probable dementia HR 0.86 (95% CI 0.72-1.02), 8.5 vs 10.2 per 1000 person-years (248 vs 293 cases); MCI HR 0.87 (95% CI 0.76-1.00); MCI or probable dementia HR 0.89 (95% CI 0.79-0.99)", "effect_size_type": "hazard ratio", "p_value": "", "cognitive_domain_affected": "clinical diagnosis (MCI / dementia)", "biomarker_endpoints": "none", "year": 2025, "publication": "Neurology 2025;104(3):e213334 (SPRINT Research Group)", "url": "https://pubmed.ncbi.nlm.nih.gov/39819096/", "doi": "10.1212/WNL.0000000000213334", "pubmed_id": "39819096", "replication_status": "not-replicated", "limitations": "Still under-accrued for dementia (216 of 326 target cases); only 59% of eligible re-contacted; telephone ascertainment; Class II evidence.", "notes": "Probable dementia remains non-significant even with extended follow-up; MCI and composite significant. MEASURED. Loaded 2026-09-22." }, { "id": "sprint-mind-2021-mri", "trial_name": "SPRINT MIND (MRI substudy)", "intervention": "intensive vs standard SBP control; brain MRI at baseline and ~4 years", "intervention_components": [ "pharmacologic", "vascular" ], "population": "SPRINT MRI substudy: 673 with baseline MRI (356 intensive, 317 standard), 454 with follow-up MRI; mean age 67.3, 40.3% women", "n_participants": 673, "age_range": "50+ (mean 67.3)", "duration": "median 3.98 years", "primary_outcome": "change in hippocampal volume, AD regional atrophy pattern, posterior cingulate cerebral blood flow, cingulum fractional anisotropy", "outcome_measure": "MRI volumetrics, ASL perfusion, DTI", "result": "harmful", "effect_size": "hippocampal volume decreased 7.45 to 7.39 cm3 (intensive) vs 7.48 to 7.46 cm3 (standard); between-group difference in change -0.033 cm3 (95% CI -0.062 to -0.003), P=0.03 (greater loss with intensive treatment); no differences in AD regional atrophy, CBF or FA", "effect_size_type": "between-group difference in 4-year hippocampal volume change (cm3)", "p_value": "0.03", "cognitive_domain_affected": "not applicable (imaging)", "biomarker_endpoints": "hippocampal volume: small greater decrease with intensive treatment; AD-signature atrophy, cerebral blood flow, white-matter integrity: no difference", "year": 2021, "publication": "Nasrallah IM et al. JAMA Neurol 2021;78(5):568-577", "url": "https://pubmed.ncbi.nlm.nih.gov/33683313/", "doi": "10.1001/jamaneurol.2021.0178", "pubmed_id": "33683313", "replication_status": "not-replicated", "limitations": "Small substudy; hippocampal difference tiny and of uncertain clinical meaning (authors relate it to greater total brain volume decrease with intensive treatment); no cognitive consequences shown.", "notes": "'harmful' label refers only to the direction of the hippocampal-volume finding, not to clinical outcomes (which favoured intensive treatment for MCI). MEASURED. Loaded 2026-09-22." }, { "id": "hope-3-cognition-2019", "trial_name": "HOPE-3 (cognitive substudy)", "intervention": "2x2 factorial: candesartan 16 mg + hydrochlorothiazide 12.5 mg vs placebo; rosuvastatin 10 mg vs placebo", "intervention_components": [ "pharmacologic", "vascular" ], "population": "adults >=70 at intermediate cardiovascular risk without known CVD, 228 centres in 21 countries; 2361 completed cognitive assessments, 1626 completed both baseline and study end; mean age 74; 59% women; 45% hypertensive", "n_participants": 2361, "age_range": "70+ (mean 74)", "duration": "median 5.7 years", "primary_outcome": "change in Digit Symbol Substitution Test; also modified MoCA and Trail Making B", "outcome_measure": "DSST change (baseline to study end)", "result": "null", "effect_size": "DSST mean difference in change: candesartan/HCTZ vs placebo -0.91 (95% CI -2.25 to 0.42); rosuvastatin vs placebo -0.54 (95% CI -1.88 to 0.80); combination vs double placebo -1.43 (95% CI -3.37 to 0.50); SBP lowered 6.0 mm Hg; LDL lowered 24.8 mg/dL", "effect_size_type": "mean difference in DSST points", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2019, "publication": "Bosch J et al. Neurology 2019;92(13):e1435-e1446", "url": "https://pubmed.ncbi.nlm.nih.gov/30814321/", "doi": "10.1212/WNL.0000000000007174", "pubmed_id": "30814321", "replication_status": "not-replicated", "limitations": "Modest BP reduction (6 mm Hg) in a population where only 45% were hypertensive; only 1626 with paired assessments; cognitive tests limited; Class II. NCT00468923.", "notes": "NULL for both BP-lowering and statin (LDL) arms on cognition -- relevant to the 2024 Lancet LDL factor. MEASURED. Loaded 2026-09-22." }, { "id": "osa-cpap-meta-2020", "trial_name": "Meta-analysis: CPAP for OSA and cognition (14 RCTs)", "intervention": "CPAP treatment for obstructive sleep apnea vs control (sham/no CPAP), pooled from randomised trials", "intervention_components": [ "sensory" ], "population": "adults with OSA in 14 RCTs (pooled n=1926)", "n_participants": 1926, "age_range": "", "duration": "varied", "primary_outcome": "cognitive domains: attention/processing speed, executive function, memory; subjective sleepiness", "outcome_measure": "standardised mean difference", "result": "mixed", "effect_size": "attention/processing speed improved only in severe OSA: SMD 0.17 (95% CI 0.02-0.31), I2=0%; no significant effects in other domains or overall", "effect_size_type": "standardised mean difference (pooled)", "p_value": "0.025 (severe OSA attention/speed)", "cognitive_domain_affected": "attention and processing speed (severe OSA only)", "biomarker_endpoints": "none", "year": 2020, "publication": "J Alzheimers Dis 2020;75(3):705-715", "url": "https://pubmed.ncbi.nlm.nih.gov/32310179/", "doi": "10.3233/JAD-200088", "pubmed_id": "32310179", "replication_status": "not-replicated", "limitations": "POOLED estimate from heterogeneous short trials, not a single trial; mostly not dementia-risk populations; sleep-apnea treatment tagged 'sensory' as nearest schema category.", "notes": "Sleep-intervention evidence summary. POOLED/MEASURED (meta-analytic). Loaded 2026-09-22." }, { "id": "maintain-your-brain-2025-primary", "trial_name": "Maintain Your Brain (MYB)", "intervention": "3-year online, personalised multidomain coaching in 2-4 modules targeting physical activity, nutrition, cognitive activity (computerised brain training) and depression/anxiety, vs control receiving module-eligible information only", "intervention_components": [ "exercise", "diet", "cognitive-training", "social" ], "population": "dementia-free community-dwelling Australians aged 55-77 with modifiable dementia risk factors (45 and Up Study cohort); 64% female", "n_participants": 6104, "age_range": "55-77", "duration": "3 years", "primary_outcome": "3-year change in global cognitive composite", "outcome_measure": "global cognitive composite z score (online neuropsychological tests)", "result": "positive", "effect_size": "change in z score 0.28 (95% CI 0.25-0.32) intervention vs 0.10 (95% CI 0.07-0.13) control; between-group difference 0.18 (95% CI 0.13-0.23)", "effect_size_type": "between-group difference in 3-year change of global cognitive composite z score", "p_value": "<0.001", "cognitive_domain_affected": "global composite", "biomarker_endpoints": "none", "year": 2025, "publication": "Brodaty H et al. Nat Med 2025;31(2):565-573", "url": "https://pubmed.ncbi.nlm.nih.gov/39875685/", "doi": "10.1038/s41591-024-03351-6", "pubmed_id": "39875685", "replication_status": "not-replicated", "limitations": "Online-only cognitive testing (potential overlap between brain-training module practice and outcome tests); single-blind; control received information only; younger and healthier than FINGER-type samples; 'social' tag reflects the depression/anxiety module (closest schema category). ACTRN12618000851268.", "notes": "Largest multidomain prevention RCT to date; largest reported effect (0.18 SD over 3 years). Adverse events 0.60% vs 0.03%. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "active-10yr-2014", "trial_name": "ACTIVE (10-year follow-up)", "intervention": "10 sessions of memory, reasoning or speed-of-processing training plus 4 booster sessions at 11 and 35 months, vs no-contact control", "intervention_components": [ "cognitive-training" ], "population": "independently living older adults in 6 US cities; mean baseline age 73.6; 26% African American", "n_participants": 2832, "age_range": "65+ (mean 73.6 at baseline)", "duration": "10 years", "primary_outcome": "targeted cognitive abilities and self-reported/performance-based everyday function (IADL)", "outcome_measure": "domain-specific cognitive tests; IADL difficulty", "result": "mixed", "effect_size": "targeted cognition at 10 y: reasoning ES 0.23 (99% CI 0.09-0.38); speed ES 0.66 (99% CI 0.43-0.88); memory training effect not maintained. IADL difficulty: memory ES 0.48 (99% CI 0.12-0.84), reasoning 0.38 (0.02-0.74), speed 0.36 (0.01-0.72). Booster: reasoning ES 0.21 (0.01-0.41), speed ES 0.62 (0.31-0.93)", "effect_size_type": "standardised effect size (Cohen d-type) vs control at 10 years", "p_value": "<0.05 (IADL comparison)", "cognitive_domain_affected": "reasoning and processing speed (domain-specific, no transfer to untrained domains reported); memory not maintained", "biomarker_endpoints": "none", "year": 2014, "publication": "Rebok GW et al. J Am Geriatr Soc 2014;62(1):16-24", "url": "https://pubmed.ncbi.nlm.nih.gov/24417410/", "doi": "10.1111/jgs.12607", "pubmed_id": "24417410", "replication_status": "not-replicated", "limitations": "Effects limited to trained abilities; substantial attrition over 10 years; IADL self-reported; no dementia endpoint in this paper (see active-20yr-claims-dementia-2026).", "notes": "'Mixed': durable domain-specific gains, no memory maintenance. MEASURED. Loaded 2026-09-22." }, { "id": "finger-2018-subgroups", "trial_name": "FINGER (prespecified subgroup analysis)", "intervention": "FINGER 2-year multidomain intervention vs regular health advice", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "FINGER participants (60-77, at risk)", "n_participants": 1260, "age_range": "60-77", "duration": "2 years", "primary_outcome": "effect modification of NTB z-score change by sex, age, education, income, baseline MMSE, BMI, BP, cholesterol, glucose, CV risk and comorbidity", "outcome_measure": "NTB z score, mixed-model repeated measures interaction tests", "result": "positive", "effect_size": "no characteristic modified intervention response (all interaction P > 0.05); benefit consistent across subgroups", "effect_size_type": "interaction P-values (no numeric effect sizes in abstract)", "p_value": ">0.05 for all interactions", "cognitive_domain_affected": "global (NTB)", "biomarker_endpoints": "none", "year": 2018, "publication": "Rosenberg A et al. Alzheimers Dement 2018;14(3):263-270", "url": "https://pubmed.ncbi.nlm.nih.gov/29055814/", "doi": "10.1016/j.jalz.2017.09.006", "pubmed_id": "29055814", "replication_status": "replicated", "limitations": "Subgroup analyses are underpowered to detect modification; absence of interaction is not proof of homogeneity.", "notes": "Contrasts with US POINTER (greater benefit at lower baseline cognition) and J-MINT (benefit only with vascular risk factors). MEASURED. Loaded 2026-09-22." }, { "id": "hearing-devices-meta-2023", "trial_name": "Meta-analysis: hearing aids/cochlear implants and cognitive decline (Yeo et al.)", "intervention": "hearing aid or cochlear implant use vs uncorrected hearing loss (pooled observational studies and trials)", "intervention_components": [ "sensory" ], "population": "adults with hearing loss; 31 studies (25 observational, 6 trials), 137,484 participants; 19 in quantitative synthesis", "n_participants": 137484, "age_range": "", "duration": "2-25 years (long-term studies)", "primary_outcome": "any cognitive decline / dementia (long-term); short-term cognitive test score change", "outcome_measure": "maximally adjusted hazard ratios; ratio of means", "result": "positive", "effect_size": "long-term cognitive decline HR 0.81 (95% CI 0.76-0.87), I2=0% (8 studies, n=126,903); short-term cognitive test scores ratio of means 1.03 (95% CI 1.02-1.04), I2=0% (11 studies, n=568)", "effect_size_type": "pooled hazard ratio; pooled ratio of means", "p_value": "", "cognitive_domain_affected": "general cognition", "biomarker_endpoints": "none", "year": 2023, "publication": "Yeo BSY et al. JAMA Neurol 2023;80(2):134-141", "url": "https://pubmed.ncbi.nlm.nih.gov/36469314/", "doi": "10.1001/jamaneurol.2022.4427", "pubmed_id": "36469314", "replication_status": "not-replicated", "limitations": "OBSERVATIONAL-dominated pooled estimate (confounding by indication, healthy-user bias); published before ACHIEVE, whose primary result was null; not a trial effect size.", "notes": "Included as context for ACHIEVE; label: POOLED/OBSERVATIONAL, not RCT-measured. Loaded 2026-09-22." }, { "id": "predimed-cognition-2015", "trial_name": "PREDIMED (Barcelona cognitive substudy)", "intervention": "Mediterranean diet supplemented with extra-virgin olive oil (1 L/week) or with mixed nuts (30 g/day) vs control diet (advice to reduce dietary fat)", "intervention_components": [ "diet" ], "population": "cognitively healthy volunteers at high cardiovascular risk, Barcelona, Spain; 52.1% women; mean age 66.9", "n_participants": 447, "age_range": "55-80 (PREDIMED design); mean 66.9", "duration": "median 4.1 years", "primary_outcome": "rate of cognitive change (memory, frontal, global composites from neuropsychological battery)", "outcome_measure": "mean z score change composites; 334 with follow-up testing", "result": "positive", "effect_size": "global composite change: +0.05 (95% CI -0.11 to 0.21) MedDiet+olive oil (P=0.005 vs control), -0.05 (-0.27 to 0.18) MedDiet+nuts, -0.38 (-0.57 to -0.18) control; frontal composite +0.23 (0.03-0.43) olive oil (P=0.003 vs control), +0.03 nuts, -0.33 control; memory composite +0.04 olive oil, +0.09 nuts (P=0.04 vs control), -0.17 control", "effect_size_type": "adjusted mean z score change from baseline per arm (composite)", "p_value": "0.005 (global, olive oil vs control); 0.003 (frontal); 0.04 (memory, nuts)", "cognitive_domain_affected": "global and frontal/executive (olive oil arm); memory (nuts arm)", "biomarker_endpoints": "none", "year": 2015, "publication": "Valls-Pedret C et al. JAMA Intern Med 2015;175(7):1094-1103", "url": "https://pubmed.ncbi.nlm.nih.gov/25961184/", "doi": "10.1001/jamainternmed.2015.1668", "pubmed_id": "25961184", "replication_status": "not-replicated", "limitations": "Single-site substudy; 25% lost to follow-up testing; control group declined unusually steeply; PREDIMED main trial was later re-analysed/republished (2018) over randomisation irregularities at some sites; age range from parent trial design, not this abstract.", "notes": "Only positive diet RCT for cognition; contrast with MIND diet trial NULL. MEASURED. Loaded 2026-09-22." }, { "id": "bp-lowering-meta-2020", "trial_name": "Meta-analysis: BP lowering and incident dementia/cognitive impairment (Hughes et al.)", "intervention": "antihypertensive blood-pressure lowering vs placebo, alternative agents or higher targets; 14 RCTs (12 in primary meta-analysis)", "intervention_components": [ "pharmacologic", "vascular" ], "population": "96,158 RCT participants; mean age 69; 42.2% women; mean baseline BP 154/83.3 mm Hg; mean follow-up 49.2 months", "n_participants": 96158, "age_range": "mean 69", "duration": "mean 4.1 years (primary outcome trials)", "primary_outcome": "dementia or cognitive impairment", "outcome_measure": "pooled odds ratio; absolute risk reduction", "result": "positive", "effect_size": "dementia or cognitive impairment OR 0.93 (95% CI 0.88-0.98), 7.0% vs 7.5%, ARR 0.39% (95% CI 0.09-0.68%), I2=0% (12 trials, n=92,135); cognitive decline OR 0.93 (95% CI 0.88-0.99), ARR 0.71% (95% CI 0.19-1.2%), I2=36.1% (8 trials); no significant change in cognitive test scores", "effect_size_type": "pooled odds ratio; absolute risk reduction", "p_value": "", "cognitive_domain_affected": "clinical dementia/cognitive impairment; test scores unchanged", "biomarker_endpoints": "none", "year": 2020, "publication": "Hughes D et al. JAMA 2020;323(19):1934-1944", "url": "https://pubmed.ncbi.nlm.nih.gov/32427305/", "doi": "10.1001/jama.2020.4249", "pubmed_id": "32427305", "replication_status": "replicated", "limitations": "POOLED from trials not designed for dementia; small absolute effect (0.39%); heterogeneous comparators; predates CRHCP (2025) and SPRINT extended follow-up.", "notes": "POOLED/MEASURED (meta-analytic). Loaded 2026-09-22." }, { "id": "hatice-2019-primary", "trial_name": "HATICE", "intervention": "coach-supported interactive internet platform for self-management of cardiovascular risk factors (BP, LDL, BMI, diet, exercise, smoking) vs static control platform, 18 months", "intervention_components": [ "vascular", "diet", "exercise" ], "population": "community-dwelling adults >=65 years at increased cardiovascular risk in the Netherlands, Finland and France", "n_participants": 2724, "age_range": "65+", "duration": "18 months", "primary_outcome": "change in standardised composite Z score of systolic BP, LDL cholesterol and BMI (cardiovascular risk profile; NOT a cognitive outcome)", "outcome_measure": "composite Z score of SBP, LDL-C, BMI; complete data in 2398 (88%)", "result": "positive", "effect_size": "composite improved 0.09 intervention vs 0.04 control; mean difference -0.05 (95% CI -0.08 to -0.01). Components: SBP -1.79 vs -0.67 mmHg (diff -1.12, 95% CI -2.51 to 0.27); BMI -0.23 vs -0.08 kg/m2 (diff -0.15, -0.28 to -0.01); LDL -0.12 vs -0.07 mmol/L (diff -0.05, -0.11 to 0.01). Cardiovascular disease HR 0.86 (95% CI 0.52-1.43)", "effect_size_type": "between-group mean difference in composite risk Z score", "p_value": "0.008", "cognitive_domain_affected": "not assessed as primary outcome (cardiovascular risk trial in the dementia-prevention pipeline; cognition was secondary and not in abstract)", "biomarker_endpoints": "SBP, LDL-C, BMI", "year": 2019, "publication": "Richard E et al. Lancet Digit Health 2019;1(8):e424-e434", "url": "https://pubmed.ncbi.nlm.nih.gov/33323224/", "doi": "10.1016/S2589-7500(19)30153-0", "pubmed_id": "33323224", "replication_status": "not-replicated", "limitations": "Primary outcome is a cardiovascular risk composite, not cognition; effect modest; open-label (blinded endpoint); individual risk-factor differences mostly not significant. ISRCTN48151589.", "notes": "Included as a dementia-prevention-motivated eHealth vascular trial (EU FP7; precursor to PRODEMOS). Abstract does not report cognitive outcomes; recorded as positive on its own (non-cognitive) primary endpoint only. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "accord-mind-2011-primary", "trial_name": "ACCORD MIND", "intervention": "intensive glycaemic control (HbA1c target <6.0%) vs standard (7.0-7.9%) in type 2 diabetes; 2x2 factorial with BP and lipid arms", "intervention_components": [ "pharmacologic", "vascular" ], "population": "adults 55-80 with type 2 diabetes, HbA1c >7.5%, high cardiovascular risk; 52 North American sites", "n_participants": 2977, "age_range": "55-80 (mean 62.5)", "duration": "40 months", "primary_outcome": "Digit Symbol Substitution Test (DSST) score at 40 months; total brain volume (MRI subset)", "outcome_measure": "DSST (n=1378 intensive vs 1416 standard); TBV MRI (230 vs 273)", "result": "null", "effect_size": "DSST difference in mean 0.32 (95% CI -0.28 to 0.91), p=0.2997; total brain volume greater in intensive group by 4.62 cm3 (95% CI 2.0 to 7.3), p=0.0007", "effect_size_type": "between-group difference in mean DSST score; difference in total brain volume", "p_value": "0.2997 (DSST); 0.0007 (TBV)", "cognitive_domain_affected": "none (processing speed unchanged)", "biomarker_endpoints": "total brain volume (MRI): favoured intensive arm", "year": 2011, "publication": "Launer LJ et al. Lancet Neurol 2011;10(11):969-77", "url": "https://pubmed.ncbi.nlm.nih.gov/21958949/", "doi": "10.1016/S1474-4422(11)70188-0", "pubmed_id": "21958949", "replication_status": "not-replicated", "limitations": "Intensive arm stopped Feb 2008 for excess mortality in parent ACCORD trial; open-label; cognitive outcome is a single test (DSST). NCT00182910.", "notes": "Null on cognition despite structural MRI benefit; authors conclude findings do not support intensive glycaemic therapy for brain outcomes. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "vitacog-2010-primary", "trial_name": "VITACOG", "intervention": "high-dose B vitamins (folic acid 0.8 mg/d, vitamin B12 0.5 mg/d, vitamin B6 20 mg/d) vs placebo, 24 months", "intervention_components": [ "supplement" ], "population": "adults >70 years with mild cognitive impairment, single centre (Oxford, UK)", "n_participants": 271, "age_range": "70+", "duration": "24 months", "primary_outcome": "change in rate of whole-brain atrophy on serial volumetric MRI", "outcome_measure": "annual whole-brain atrophy rate (MRI subset n=168 completers: 85 active, 83 placebo)", "result": "positive", "effect_size": "mean atrophy rate per year 0.76% (95% CI 0.63-0.90) active vs 1.08% (0.94-1.22) placebo; in participants with baseline homocysteine >13 umol/L atrophy rate 53% lower with treatment", "effect_size_type": "between-group difference in annual brain atrophy rate (%/year); relative reduction in high-homocysteine subgroup", "p_value": "0.001", "cognitive_domain_affected": "abstract reports only that greater atrophy was associated with lower final cognitive scores; no primary cognitive endpoint", "biomarker_endpoints": "whole-brain atrophy rate (MRI); plasma homocysteine", "year": 2010, "publication": "Smith AD et al. PLoS One 2010;5(9):e12244", "url": "https://pubmed.ncbi.nlm.nih.gov/20838622/", "doi": "10.1371/journal.pone.0012244", "pubmed_id": "20838622", "replication_status": "not-replicated", "limitations": "Small single-centre trial; MRI endpoint in a self-selected subset (187 of 271 volunteered; 168 completed); surrogate (atrophy) not clinical outcome; no large confirmatory trial has replicated a dementia-incidence benefit. ISRCTN94410159.", "notes": "Positive on a biomarker surrogate only. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "guidage-2012-primary", "trial_name": "GuidAge", "intervention": "standardised Ginkgo biloba extract EGb761 120 mg twice daily vs placebo, 5 years", "intervention_components": [ "supplement" ], "population": "adults >=70 years with spontaneous memory complaints reported to primary-care physicians, France", "n_participants": 2854, "age_range": "70+", "duration": "5 years", "primary_outcome": "conversion to probable Alzheimer's disease", "outcome_measure": "incident probable AD (1406 ginkgo vs 1414 placebo received >=1 dose)", "result": "null", "effect_size": "61 AD cases (1.2 per 100 person-years) ginkgo vs 73 (1.4 per 100 PY) placebo; HR 0.84 (95% CI 0.60-1.18); risk not proportional over time. Mortality HR 0.94 (0.69-1.28); stroke RR 1.12 (0.77-1.63)", "effect_size_type": "hazard ratio", "p_value": "0.306", "cognitive_domain_affected": "none (incident AD not reduced)", "biomarker_endpoints": "none", "year": 2012, "publication": "Vellas B et al. Lancet Neurol 2012;11(10):851-9", "url": "https://pubmed.ncbi.nlm.nih.gov/22959217/", "doi": "10.1016/S1474-4422(12)70206-5", "pubmed_id": "22959217", "replication_status": "replicated", "limitations": "Industry-funded (Ipsen); non-proportional hazards noted; memory-complaint population. NCT00276510.", "notes": "Null result consistent with GEM (US) -- see gem-ginkgo-2008-primary; 'replicated' here means the NULL finding was replicated across two large RCTs. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "whims-2003-estrogen-progestin", "trial_name": "WHIMS (Women's Health Initiative Memory Study)", "intervention": "conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg daily vs placebo", "intervention_components": [ "pharmacologic" ], "population": "postmenopausal women >=65 years free of probable dementia, from 39 WHI clinical centres (USA)", "n_participants": 4532, "age_range": "65+", "duration": "mean 4.05 years (SD 1.19) to last 3MSE", "primary_outcome": "incidence of probable dementia", "outcome_measure": "adjudicated probable dementia (2229 E+P vs 2303 placebo)", "result": "harmful", "effect_size": "probable dementia HR 2.05 (95% CI 1.21-3.48); 45 vs 22 per 10,000 person-years (40 vs 21 cases); 23 additional dementia cases per 10,000 women per year. MCI HR 1.07 (95% CI 0.74-1.55), 63 vs 59 per 10,000 PY", "effect_size_type": "hazard ratio; absolute excess incidence", "p_value": "0.01 (dementia); 0.72 (MCI)", "cognitive_domain_affected": "clinical dementia diagnosis (AD most common classification in both arms)", "biomarker_endpoints": "none", "year": 2003, "publication": "Shumaker SA et al. JAMA 2003;289(20):2651-62", "url": "https://pubmed.ncbi.nlm.nih.gov/12771112/", "doi": "10.1001/jama.289.20.2651", "pubmed_id": "12771112", "replication_status": "not-replicated", "limitations": "Small number of events (61); women >=65 (late initiation), so does not test the 'critical window' hypothesis; parent WHI E+P trial stopped July 2002 for other harms.", "notes": "Landmark HARMFUL prevention result: combined HRT doubled probable-dementia risk. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "hyvet-cog-2008-primary", "trial_name": "HYVET-COG", "intervention": "indapamide SR 1.5 mg with optional perindopril 2-4 mg vs placebo (target BP 150/80)", "intervention_components": [ "pharmacologic", "vascular" ], "population": "hypertensive adults >=80 years (SBP 160-200, DBP <110) without dementia at baseline", "n_participants": 3336, "age_range": "80+", "duration": "mean 2.2 years follow-up (trial stopped early 2007)", "primary_outcome": "incident dementia", "outcome_measure": "incident dementia by expert review (MMSE-triggered); 1687 treatment vs 1649 placebo", "result": "null", "effect_size": "incident dementia 33 vs 38 per 1000 patient-years (263 cases total); HR 0.86 (95% CI 0.67-1.09). BP difference at 2 years: -15/-5.9 mmHg. Pooled with prior placebo-controlled trials: HR 0.87 (0.76-1.00), p=0.045", "effect_size_type": "hazard ratio", "p_value": "not significant (HYVET alone); 0.045 (meta-analysis incl. HYVET)", "cognitive_domain_affected": "clinical dementia diagnosis; no significant effect", "biomarker_endpoints": "blood pressure", "year": 2008, "publication": "Peters R et al. Lancet Neurol 2008;7(8):683-9", "url": "https://pubmed.ncbi.nlm.nih.gov/18614402/", "doi": "10.1016/S1474-4422(08)70143-1", "pubmed_id": "18614402", "replication_status": "replicated", "limitations": "Stopped early for stroke/mortality benefit so short follow-up; MMSE-based case ascertainment; very old population. NCT00122811.", "notes": "Null alone; direction consistent with later SPRINT MIND and Hughes 2020 meta-analysis (see bp-lowering-meta-2020). MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "syst-eur-1998-dementia", "trial_name": "Syst-Eur (vascular dementia project)", "intervention": "nitrendipine 10-40 mg/d with optional enalapril and/or hydrochlorothiazide vs placebo (target SBP <150)", "intervention_components": [ "pharmacologic", "vascular" ], "population": "adults >=60 with isolated systolic hypertension (SBP 160-219, DBP <95), no dementia; Europe", "n_participants": 2418, "age_range": "60+", "duration": "median 2.0 years", "primary_outcome": "incidence of dementia (DSM-III-R, MMSE-screened)", "outcome_measure": "incident dementia: 1238 active vs 1180 placebo", "result": "positive", "effect_size": "dementia incidence reduced 50%: 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 cases); authors estimate 19 dementia cases prevented per 1000 patients treated 5 years", "effect_size_type": "relative reduction in incidence rate; cases per 1000 patient-years", "p_value": "0.05", "cognitive_domain_affected": "clinical dementia diagnosis; MMSE unchanged on average in both arms", "biomarker_endpoints": "blood pressure (-8.3/-3.8 mmHg)", "year": 1998, "publication": "Forette F et al. Lancet 1998;352(9137):1347-51", "url": "https://pubmed.ncbi.nlm.nih.gov/9802273/", "doi": "10.1016/s0140-6736(98)03086-4", "pubmed_id": "9802273", "replication_status": "not-replicated", "limitations": "Only 32 dementia events; borderline p=0.05; short follow-up; MMSE-triggered ascertainment; effect size larger than any subsequent BP trial.", "notes": "Earliest positive RCT signal for antihypertensive dementia prevention; magnitude not reproduced by HYVET-COG, SPRINT MIND or CRHCP. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "adapt-fs-2015-cognition", "trial_name": "ADAPT / ADAPT-FS (Alzheimer's Disease Anti-inflammatory Prevention Trial)", "intervention": "naproxen or celecoxib vs placebo for 1-3 years (treatment stopped 2004), with follow-up to 2007 and re-evaluation 2010-11", "intervention_components": [ "pharmacologic" ], "population": "older adults with a family history of Alzheimer's disease (USA)", "n_participants": 2356, "age_range": "", "duration": "treatment 1-3 years; cognitive follow-up to 2010-11", "primary_outcome": "trajectories of cognitive test scores (seven yearly evaluations; global composite)", "outcome_measure": "seven in-person cognitive measures + global composite; telephone battery at ADAPT-FS (1537 re-evaluated)", "result": "null", "effect_size": "no important differences over time by treatment group on any cognitive measure or the global composite (abstract gives no numeric estimate)", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2015, "publication": "ADAPT-FS Research Group. Alzheimers Dement 2015;11(2):216-25.e1", "url": "https://pubmed.ncbi.nlm.nih.gov/25022541/", "doi": "10.1016/j.jalz.2014.03.009", "pubmed_id": "25022541", "replication_status": "not-replicated", "limitations": "Treatment halted early (2004) for cardiovascular safety concerns with celecoxib/naproxen class; abstract lacks numeric effect estimates; attrition to 1537 at ADAPT-FS. NCT00007189, NCT01417130.", "notes": "Null for NSAID prevention; abstract provides no effect size so effect_size fields left empty by design. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "semaglutide-tte-2024-observational", "trial_name": "Semaglutide target-trial emulation (TriNetX EHR, Wang et al.)", "intervention": "semaglutide vs seven other antidiabetic drug classes in type 2 diabetes (OBSERVATIONAL target-trial emulation, not an RCT)", "intervention_components": [ "pharmacologic" ], "population": "1,094,761 eligible US patients with type 2 diabetes and no prior AD diagnosis, from EHR database of 116 million patients", "n_participants": 1094761, "age_range": "", "duration": "3-year follow-up", "primary_outcome": "first-ever diagnosis of Alzheimer's disease", "outcome_measure": "first AD diagnosis (Cox proportional hazards; 7 emulated trials)", "result": "positive", "effect_size": "HR 0.33 (95% CI 0.21-0.51) vs insulin (strongest); HR 0.59 (95% CI 0.37-0.95) vs other GLP-1RAs (weakest); described as 40-70% lower risk across comparators", "effect_size_type": "hazard ratio (observational, propensity-matched)", "p_value": "", "cognitive_domain_affected": "AD diagnosis codes (no cognitive testing)", "biomarker_endpoints": "none", "year": 2024, "publication": "Wang W et al. Alzheimers Dement 2024;20(12):8661-8672", "url": "https://pubmed.ncbi.nlm.nih.gov/39445596/", "doi": "10.1002/alz.14313", "pubmed_id": "39445596", "replication_status": "not-replicated", "limitations": "OBSERVATIONAL/EHR-derived, not randomised; diagnosis-code outcome; confounding by indication and healthy-user bias possible; the RCT test of semaglutide (evoke/evoke+, symptomatic AD) was NULL.", "notes": "MODELLED/OBSERVATIONAL association, included to document the GLP-1 prevention hypothesis that motivated evoke; contrast with evoke-evokeplus-2026-primary. Source: PubMed abstract loaded 2026-09-22.", "evidence_type": "observational-target-trial-emulation" }, { "id": "achieve-2025-risk-quartile-secondary", "trial_name": "ACHIEVE (secondary: benefit by predicted risk of cognitive decline)", "intervention": "hearing intervention (audiological counselling + hearing aids) vs health education control", "intervention_components": [ "sensory" ], "population": "977 ACHIEVE participants; predicted-risk model developed in 2692 dementia-free ARIC participants", "n_participants": 977, "age_range": "70-84", "duration": "3 years", "primary_outcome": "interaction between predicted risk of cognitive decline and randomisation on 3-year cognitive decline", "outcome_measure": "global cognition factor score", "result": "positive", "effect_size": "among participants in the top quartile of predicted risk, 3-year cognitive decline was 61.6% (95% CI 33.7%-94.1%) slower with hearing intervention than control", "effect_size_type": "relative reduction in 3-year cognitive decline (subgroup)", "p_value": "", "cognitive_domain_affected": "global cognition (high-risk subgroup)", "biomarker_endpoints": "none", "year": 2025, "publication": "Pike JR et al. Alzheimers Dement 2025;21(5):e70156", "url": "https://pubmed.ncbi.nlm.nih.gov/40369891/", "doi": "10.1002/alz.70156", "pubmed_id": "40369891", "replication_status": "not-replicated", "limitations": "Secondary/subgroup analysis; primary ACHIEVE result was null; effect-modification analyses are hypothesis-generating. NCT03243422.", "notes": "Extends the ACHIEVE ARIC-cohort finding (48% reduction) to a risk-score-defined subgroup. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "achieve-2026-gfap-nfl-secondary", "trial_name": "ACHIEVE (secondary: plasma GFAP and NfL)", "intervention": "hearing intervention vs health education control", "intervention_components": [ "sensory" ], "population": "ACHIEVE participants recruited from the ARIC cohort with plasma at baseline and 3 years (n=164; mean age 78.1)", "n_participants": 164, "age_range": "70-84 (mean 78.1)", "duration": "3 years", "primary_outcome": "3-year change in plasma GFAP (neuroinflammation) and NfL (neurodegeneration)", "outcome_measure": "inverse-normal transformed GFAP and NfL, covariate-adjusted linear mixed models", "result": "mixed", "effect_size": "GFAP change: intervention -0.026 (95% CI -0.144 to 0.093) vs control 0.149 (0.039 to 0.260); difference -0.175 (95% CI -0.322 to -0.028). NfL: 0.171 vs 0.330; difference -0.159 (95% CI -0.348 to 0.029)", "effect_size_type": "between-group difference in 3-year change of transformed biomarker (SD-like units)", "p_value": "0.019 (GFAP); 0.098 (NfL)", "cognitive_domain_affected": "not applicable (biomarker outcome)", "biomarker_endpoints": "plasma GFAP (significant), plasma NfL (not significant)", "year": 2026, "publication": "Pike JR et al. EClinicalMedicine 2026;99:104164", "url": "https://pubmed.ncbi.nlm.nih.gov/42733779/", "doi": "10.1016/j.eclinm.2026.104164", "pubmed_id": "42733779", "replication_status": "not-replicated", "limitations": "Small ARIC-only subsample (n=164); non-specific biomarkers; secondary analysis. NCT03243422.", "notes": "First RCT biomarker evidence for a hearing intervention. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "finger-2018-apoe-subgroup", "trial_name": "FINGER (prespecified APOE e4 subgroup analysis)", "intervention": "multidomain lifestyle (diet, exercise, cognitive training, vascular risk management) vs general health advice", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "FINGER participants with APOE genotype (1109 analysed: 362 e4 carriers, 747 noncarriers)", "n_participants": 1109, "age_range": "60-77 (mean 69.3)", "duration": "2 years", "primary_outcome": "change in NTB total score by APOE e4 status", "outcome_measure": "annual NTB total score change, modified ITT", "result": "positive", "effect_size": "intervention-control difference in annual NTB change 0.037 (95% CI 0.001-0.073) in e4 carriers vs 0.014 (95% CI -0.011 to 0.039) in noncarriers; carrier-noncarrier difference in effect 0.023 (95% CI -0.021 to 0.067), not significant", "effect_size_type": "between-group difference in annual NTB Z score change", "p_value": "", "cognitive_domain_affected": "global cognition (NTB)", "biomarker_endpoints": "APOE genotype (effect modifier)", "year": 2018, "publication": "Solomon A et al. JAMA Neurol 2018;75(4):462-470", "url": "https://pubmed.ncbi.nlm.nih.gov/29356827/", "doi": "10.1001/jamaneurol.2017.4365", "pubmed_id": "29356827", "replication_status": "replicated", "limitations": "Subgroup analysis; interaction not significant; benefit in noncarriers alone not significant. NCT01041989.", "notes": "Supports benefit regardless of APOE status; US POINTER later also found no APOE interaction (P=0.95). MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "singer-ongoing-protocol", "trial_name": "SINGER (Singapore)", "intervention": "structured multidomain lifestyle (diet training, supervised then unsupervised exercise, cognitive training, vascular risk management) vs self-guided intervention, 2 years", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "Singapore adults 60-77 with CAIDE score >=6, >=1 LIBRA lifestyle risk, MoCA 18-27", "n_participants": 1200, "age_range": "60-77", "duration": "2 years", "primary_outcome": "global cognition (modified Neuropsychological Test Battery)", "outcome_measure": "modified NTB composite", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "planned: brain and retinal imaging, blood biomarkers", "year": 2022, "publication": "Xu X et al. J Prev Alzheimers Dis 2022;9(1):40-48 (protocol)", "url": "https://pubmed.ncbi.nlm.nih.gov/35098972/", "doi": "10.14283/jpad.2022.5", "pubmed_id": "35098972", "replication_status": "ongoing", "limitations": "Protocol only; planned n=1200; no results located in PubMed as of 2026-09-22.", "notes": "World-Wide FINGERS member. Result fields intentionally empty (ongoing). Source: PubMed abstract loaded 2026-09-22." }, { "id": "au-arrow-ongoing-protocol", "trial_name": "AU-ARROW (Australia)", "intervention": "multimodal lifestyle (aerobic + resistance exercise, MIND diet advice, BrainHQ cognitive training, medical monitoring/health education) vs health education and coaching, 2 years", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "Australian adults 55-79", "n_participants": 600, "age_range": "55-79", "duration": "2 years", "primary_outcome": "change in global composite cognitive score", "outcome_measure": "global composite cognitive score", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "planned: blood biomarkers, amyloid PET, MRI, retinal biomarkers", "year": 2024, "publication": "Gardener SL et al. Alzheimers Dement (N Y) 2024;10(2):e12466 (protocol)", "url": "https://pubmed.ncbi.nlm.nih.gov/38596483/", "doi": "10.1002/trc2.12466", "pubmed_id": "38596483", "replication_status": "ongoing", "limitations": "Protocol only (planned n=600); no results located as of 2026-09-22.", "notes": "World-Wide FINGERS member mirroring FINGER and US POINTER. Source: PubMed abstract loaded 2026-09-22." }, { "id": "met-finger-ongoing-protocol", "trial_name": "MET-FINGER", "intervention": "FINGER 2.0 multidomain lifestyle (diet, physical activity, cognitive training, vascular/metabolic monitoring, social interaction) +/- metformin 1000-2000 mg/day (trial-within-trial, double-blind vs placebo) vs regular health advice", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social", "pharmacologic" ], "population": "APOE e4-enriched adults 60-79 at increased dementia risk; UK, Finland, Sweden", "n_participants": 600, "age_range": "60-79", "duration": "2 years", "primary_outcome": "change in global cognition (NTB)", "outcome_measure": "NTB composite", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "planned: metabolic/vascular risk markers", "year": 2024, "publication": "Barbera M et al. Alzheimers Res Ther 2024;16(1):23 (protocol)", "url": "https://pubmed.ncbi.nlm.nih.gov/38297399/", "doi": "10.1186/s13195-023-01355-x", "pubmed_id": "38297399", "replication_status": "ongoing", "limitations": "Phase IIb proof-of-concept protocol; planned n=600; no results located as of 2026-09-22. NCT05109169.", "notes": "First lifestyle + repurposed-drug combination prevention trial. Source: PubMed abstract loaded 2026-09-22." }, { "id": "lancet2024-paf-less-education", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Less education' (early-life)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "5% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "early-life", "paf_weighted_pct": 5 }, { "id": "lancet2024-paf-hearing-impairment", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Hearing impairment' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "7% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment. Manuscript text: new random-effects meta-analysis of 6 studies (n=666,370, follow-up 6-12 y): hearing loss vs normal hearing HR 1.37 (1.00-1.87), I2=80%, unadjusted for hearing-aid use (conservative).", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 7, "relative_risk": "HR 1.37 (95% CI 1.00-1.87)" }, { "id": "lancet2024-paf-high-ldl-cholesterol", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'High LDL cholesterol' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "7% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 7 }, { "id": "lancet2024-paf-depression", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Depression' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "3% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment. Manuscript text: new random-effects meta-analysis of 7 studies with 10-14-year follow-up: RR 2.25 (1.69-2.98), I2=82.8%.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 3, "relative_risk": "RR 2.25 (95% CI 1.69-2.98)" }, { "id": "lancet2024-paf-traumatic-brain-injury", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Traumatic brain injury' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "3% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 3 }, { "id": "lancet2024-paf-physical-inactivity", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Physical inactivity' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "2% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 2 }, { "id": "lancet2024-paf-diabetes", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Diabetes' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "2% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 2 }, { "id": "lancet2024-paf-smoking", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Smoking' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "2% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 2 }, { "id": "lancet2024-paf-hypertension", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Hypertension' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "2% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 2 }, { "id": "lancet2024-paf-obesity", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Obesity' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "1% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 1 }, { "id": "lancet2024-paf-excessive-alcohol", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Excessive alcohol' (midlife)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "1% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "midlife", "paf_weighted_pct": 1 }, { "id": "lancet2024-paf-social-isolation", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Social isolation' (late-life)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "5% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "late-life", "paf_weighted_pct": 5 }, { "id": "lancet2024-paf-air-pollution", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Air pollution' (late-life)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "3% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment.", "evidence_type": "modelled-PAF", "life_stage": "late-life", "paf_weighted_pct": 3 }, { "id": "lancet2024-paf-visual-impairment", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Visual impairment (uncorrected vision loss)' (late-life)", "intervention_components": [], "population": "worldwide (risk-factor prevalence from largest recent worldwide meta-analyses; communality from HUNT study, Norway, ~37,000 participants aged >=45)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted population attributable fraction of dementia cases attributable to the risk factor (adjusted for communality)", "outcome_measure": "weighted PAF (%), rounded to whole number as displayed in Figure 9", "result": "positive", "effect_size": "2% of dementia cases (weighted PAF, rounded)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED estimate assuming causality; whole-number rounding from Figure 9 (the accepted manuscript at UCL Discovery does not include the Table 1 body with RR, prevalence, communality and unweighted PAF -- those decimals could not be obtained and are NOT recorded here); prevalence data disproportionately from HICs; LDL prevalence from a single cohort; HUNT communality sample lacks ethnic diversity (per authors).", "notes": "MODELLED / PROJECTED, not a trial result. Value read directly from Figure 9 ('Population attributable fraction of potentially modifiable risk factors for dementia') of the author accepted manuscript (UCL Discovery eprint 10196488), loaded 2026-09-22. Key: 'Percentage reduction in cases of dementia if this risk factor is eliminated'. Text states overall PAF for all 14 factors = 45.3%; figure total 45%. New factors vs 2020: high LDL cholesterol and vision impairment. Manuscript text cites a meta-analysis: visual impairment and all-cause dementia RR 1.38 (1.19-1.59, n=37,705).", "evidence_type": "modelled-PAF", "life_stage": "late-life", "paf_weighted_pct": 2 }, { "id": "lancet2024-paf-total-14-factors", "trial_name": "Lancet Commission 2024 (population attributable fraction)", "intervention": "MODELLED: elimination of all 14 potentially modifiable risk factors", "intervention_components": [], "population": "worldwide", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "overall weighted PAF for 14 risk factors", "outcome_measure": "weighted PAF (%)", "result": "positive", "effect_size": "45.3% of dementia cases (text); 45% (Figure 9)", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2024, "publication": "Livingston G et al. Lancet 2024;404(10452):572-628", "url": "https://discovery.ucl.ac.uk/10196488/1/Livingston_Lancet%20Commission%20accepted%20version.pdf", "doi": "10.1016/S0140-6736(24)01296-0", "pubmed_id": "39096926", "replication_status": "ongoing", "limitations": "MODELLED; assumes causality; five principal components explained 54% of variance among the 14 factors (substantial overlap) so weighted PAFs adjust for communality; see per-factor rows.", "notes": "MODELLED. Quote from manuscript: 'We estimated that the PAF for all 14 risk factors was 45.3%.' Loaded from UCL Discovery accepted manuscript 2026-09-22.", "evidence_type": "modelled-PAF", "paf_weighted_pct": 45.3 }, { "id": "lancet2020-paf-less-education", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Less education' (early-life (<45))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 7.1%; unweighted PAF 19.4%; RR 1.6 (1.3-2.0); prevalence 40.0%; communality 61.2%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "early-life (<45)", "relative_risk": "1.6 (1.3-2.0)", "prevalence_pct": 40.0, "communality_pct": 61.2, "paf_unweighted_pct": 19.4, "paf_weighted_pct": 7.1 }, { "id": "lancet2020-paf-hearing-loss", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Hearing loss' (midlife (45-65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 8.2%; unweighted PAF 22.2%; RR 1.9 (1.4-2.7); prevalence 31.7%; communality 45.6%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "midlife (45-65)", "relative_risk": "1.9 (1.4-2.7)", "prevalence_pct": 31.7, "communality_pct": 45.6, "paf_unweighted_pct": 22.2, "paf_weighted_pct": 8.2 }, { "id": "lancet2020-paf-traumatic-brain-injury", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Traumatic brain injury' (midlife (45-65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 3.4%; unweighted PAF 9.2%; RR 1.8 (1.5-2.2); prevalence 12.1%; communality 55.2%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "midlife (45-65)", "relative_risk": "1.8 (1.5-2.2)", "prevalence_pct": 12.1, "communality_pct": 55.2, "paf_unweighted_pct": 9.2, "paf_weighted_pct": 3.4 }, { "id": "lancet2020-paf-hypertension", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Hypertension' (midlife (45-65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 1.9%; unweighted PAF 5.1%; RR 1.6 (1.2-2.2); prevalence 8.9%; communality 68.3%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "midlife (45-65)", "relative_risk": "1.6 (1.2-2.2)", "prevalence_pct": 8.9, "communality_pct": 68.3, "paf_unweighted_pct": 5.1, "paf_weighted_pct": 1.9 }, { "id": "lancet2020-paf-alcohol", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Alcohol (>21 units/week)' (midlife (45-65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 0.8%; unweighted PAF 2.1%; RR 1.2 (1.1-1.3); prevalence 11.8%; communality 73.3%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "midlife (45-65)", "relative_risk": "1.2 (1.1-1.3)", "prevalence_pct": 11.8, "communality_pct": 73.3, "paf_unweighted_pct": 2.1, "paf_weighted_pct": 0.8 }, { "id": "lancet2020-paf-obesity", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Obesity (BMI >=30)' (midlife (45-65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 0.7%; unweighted PAF 2.0%; RR 1.6 (1.3-1.9); prevalence 3.4%; communality 58.5%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "midlife (45-65)", "relative_risk": "1.6 (1.3-1.9)", "prevalence_pct": 3.4, "communality_pct": 58.5, "paf_unweighted_pct": 2.0, "paf_weighted_pct": 0.7 }, { "id": "lancet2020-paf-smoking", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Smoking' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 5.2%; unweighted PAF 14.1%; RR 1.6 (1.2-2.2); prevalence 27.4%; communality 62.3%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.6 (1.2-2.2)", "prevalence_pct": 27.4, "communality_pct": 62.3, "paf_unweighted_pct": 14.1, "paf_weighted_pct": 5.2 }, { "id": "lancet2020-paf-depression", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Depression' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 3.9%; unweighted PAF 10.6%; RR 1.9 (1.6-2.3); prevalence 13.2%; communality 69.8%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.9 (1.6-2.3)", "prevalence_pct": 13.2, "communality_pct": 69.8, "paf_unweighted_pct": 10.6, "paf_weighted_pct": 3.9 }, { "id": "lancet2020-paf-social-isolation", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Social isolation' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 3.5%; unweighted PAF 4.2%; RR 1.6 (1.3-1.9); prevalence 11.0%; communality 28.1%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.6 (1.3-1.9)", "prevalence_pct": 11.0, "communality_pct": 28.1, "paf_unweighted_pct": 4.2, "paf_weighted_pct": 3.5 }, { "id": "lancet2020-paf-physical-inactivity", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Physical inactivity' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 1.6%; unweighted PAF 9.6%; RR 1.4 (1.2-1.7); prevalence 17.7%; communality 55.2%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.4 (1.2-1.7)", "prevalence_pct": 17.7, "communality_pct": 55.2, "paf_unweighted_pct": 9.6, "paf_weighted_pct": 1.6 }, { "id": "lancet2020-paf-diabetes", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Diabetes' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 1.1%; unweighted PAF 3.1%; RR 1.5 (1.3-1.8); prevalence 6.4%; communality 71.4%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.5 (1.3-1.8)", "prevalence_pct": 6.4, "communality_pct": 71.4, "paf_unweighted_pct": 3.1, "paf_weighted_pct": 1.1 }, { "id": "lancet2020-paf-air-pollution", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of risk factor 'Air pollution' (later life (>65))", "intervention_components": [], "population": "worldwide (communality from a UK community sample of >10,000 adults)", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "weighted PAF of dementia attributable to the risk factor", "outcome_measure": "Table 1: relative risk (95% CI), prevalence, communality, unweighted PAF, weighted PAF", "result": "positive", "effect_size": "weighted PAF 2.3%; unweighted PAF 6.3%; RR 1.1 (1.1-1.1); prevalence 75.0%; communality 13.3%", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; assumes causality; RRs and prevalences for nine original factors carried over from the 2017 Commission; TBI communality imputed as mean of other 11; cohabitation used as proxy for social contact and urbanicity for air pollution.", "notes": "MODELLED / PROJECTED. Verbatim from Table 1 'PAF for 12 dementia risk factors' in PMC7392084 full text (loaded 2026-09-22). Overall weighted PAF = 39.7%. Superseded by the 2024 Commission's 14-factor model (see lancet2024-paf-* rows).", "evidence_type": "modelled-PAF", "life_stage": "later life (>65)", "relative_risk": "1.1 (1.1-1.1)", "prevalence_pct": 75.0, "communality_pct": 13.3, "paf_unweighted_pct": 6.3, "paf_weighted_pct": 2.3 }, { "id": "lancet2020-paf-total-12-factors", "trial_name": "Lancet Commission 2020 (population attributable fraction)", "intervention": "MODELLED: elimination of all 12 potentially modifiable risk factors", "intervention_components": [], "population": "worldwide", "n_participants": "", "age_range": "", "duration": "", "primary_outcome": "overall weighted PAF", "outcome_measure": "weighted PAF (%)", "result": "positive", "effect_size": "39.7% of dementia cases", "effect_size_type": "weighted population attributable fraction (%)", "p_value": "", "cognitive_domain_affected": "all-cause dementia incidence", "biomarker_endpoints": "", "year": 2020, "publication": "Livingston G et al. Lancet 2020;396(10248):413-446", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7392084/", "doi": "10.1016/S0140-6736(20)30367-6", "pubmed_id": "32738937", "replication_status": "replicated", "limitations": "MODELLED; four principal components explained 55% of variance across 11 factors (substantial overlap).", "notes": "MODELLED. Table 1 footnote: 'Overall weighted PAF=39·7%'. PMC7392084 loaded 2026-09-22.", "evidence_type": "modelled-PAF", "paf_weighted_pct": 39.7 }, { "id": "ornish-2024-intensive-lifestyle-mci", "trial_name": "Ornish intensive lifestyle trial (MCI/early AD)", "intervention": "20-week intensive multidomain lifestyle programme (whole-food plant-based diet, exercise, stress management, group support) vs wait-list usual care", "intervention_components": [ "diet", "exercise", "social" ], "population": "adults 45-90 with MCI or early dementia due to AD (MoCA >=18), plasma Abeta42/40 <0.0672 in all; multicentre USA", "n_participants": 51, "age_range": "45-90 (mean 73.5)", "duration": "20 weeks", "primary_outcome": "change in CGIC, ADAS-Cog, CDR-SB, CDR-Global", "outcome_measure": "CGIC (Fisher exact), ADAS-Cog/CDR-SB/CDR-G (Mann-Whitney)", "result": "positive", "effect_size": "between-group differences significant for CGIC (p=0.001), CDR-SB (p=0.032), CDR-Global (p=0.037); borderline ADAS-Cog (p=0.053); abstract gives no numeric effect estimates. Plasma Abeta42/40 ratio rose in intervention and fell in control (p=0.003)", "effect_size_type": "", "p_value": "0.001 (CGIC); 0.032 (CDR-SB); 0.037 (CDR-G); 0.053 (ADAS-Cog)", "cognitive_domain_affected": "global clinical/cognitive scales", "biomarker_endpoints": "plasma Abeta42/40 (increased in intervention), microbiome", "year": 2024, "publication": "Ornish D et al. Alzheimers Res Ther 2024;16(1):122", "url": "https://pubmed.ncbi.nlm.nih.gov/38849944/", "doi": "10.1186/s13195-024-01482-z", "pubmed_id": "38849944", "replication_status": "not-replicated", "limitations": "Very small (n=51), phase 2, 20 weeks, wait-list (unblinded) control, retrospectively registered (NCT04606420), symptomatic population (treatment not primary prevention), no numeric effect sizes in abstract; nonparametric tests on ordinal scales.", "notes": "Included for completeness of the multidomain-lifestyle literature; symptomatic AD, so not a prevention trial per se. MEASURED. Source: PubMed abstract loaded 2026-09-22." }, { "id": "prodemos-2024-primary", "trial_name": "PRODEMOS", "intervention": "coach-supported mobile health (smartphone app) lifestyle intervention targeting dementia risk factors vs control, 12-18 months", "intervention_components": [ "vascular", "diet", "exercise" ], "population": "adults 55-75 with >=2 dementia risk factors: low socioeconomic status in the UK, or general population in China", "n_participants": 1488, "age_range": "55-75", "duration": "mean 16 months (SD 2.5)", "primary_outcome": "change in CAIDE dementia risk score (NOT a cognitive outcome)", "outcome_measure": "CAIDE score change; 1229 (83%) analysed (734 intervention vs 754 control randomised)", "result": "positive", "effect_size": "CAIDE score improved 0.16 points intervention vs 0.01 control; mean difference -0.16 (95% CI -0.29 to -0.03)", "effect_size_type": "between-group mean difference in CAIDE risk score (points)", "p_value": "", "cognitive_domain_affected": "not measured as primary outcome (risk-score surrogate)", "biomarker_endpoints": "cardiovascular risk factors within CAIDE", "year": 2024, "publication": "Moll van Charante EP et al. Lancet Healthy Longev 2024;5(6):e431-e442", "url": "https://pubmed.ncbi.nlm.nih.gov/38763155/", "doi": "10.1016/S2666-7568(24)00068-0", "pubmed_id": "38763155", "replication_status": "not-replicated", "limitations": "Surrogate risk-score outcome; modest effect (0.16 CAIDE points); only 10% of invited responded; 50% sustained participation; open-label; authors state a larger long-follow-up RCT is needed to show cognitive/dementia effects. ISRCTN15986016.", "notes": "Successor to HATICE; effectiveness-implementation hybrid. Positive on risk-score only. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "agewell-de-2024-libra-secondary", "trial_name": "AgeWell.de", "intervention": "pragmatic multicomponent lifestyle intervention delivered via general practice (optimisation of nutrition, medication, physical, social and cognitive activity) vs general health advice, 2 years", "intervention_components": [ "diet", "exercise", "cognitive-training", "social", "vascular", "pharmacologic" ], "population": "German primary-care patients 60-77 with CAIDE score >=9 (cluster-randomised by GP practice); LIBRA analysis n=461 with complete 24-month data", "n_participants": 461, "age_range": "60-77", "duration": "24 months", "primary_outcome": "secondary analysis: change in LIBRA (LIfestyle for BRAin health) dementia risk index", "outcome_measure": "LIBRA index and components, generalized linear models", "result": "positive", "effect_size": "LIBRA score reduced by b = -0.63 (95% CI -1.14 to -0.12); driven by diet (OR 1.60, 95% CI 1.16-2.22) and hypertension (OR 1.61, 95% CI 1.19-2.18) improvements", "effect_size_type": "regression coefficient (LIBRA points); odds ratios for component improvement", "p_value": "", "cognitive_domain_affected": "not applicable (risk-index outcome); the trial's primary cognitive outcome publication was NOT located in PubMed/Europe PMC as of 2026-09-22", "biomarker_endpoints": "blood pressure (hypertension component)", "year": 2024, "publication": "Zülke AE et al. Alzheimers Dement 2024;20(8):5684-5694", "url": "https://pubmed.ncbi.nlm.nih.gov/38967275/", "doi": "10.1002/alz.14097", "pubmed_id": "38967275", "replication_status": "not-replicated", "limitations": "Secondary analysis on a risk index, not cognition; only 461 of the trial's ~819 participants had complete LIBRA data; several risk factors did not improve. DRKS00013555.", "notes": "World-Wide FINGERS member (Germany). Cost-effectiveness paper (PMID 39759949) reports 819 participants (378 intervention/441 control), ICER EUR 17,149/QALY. MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "agewell-de-2025-imaging", "trial_name": "AgeWell.de (Leipzig imaging substudy)", "intervention": "FINGER-based multimodal lifestyle intervention vs control", "intervention_components": [ "diet", "exercise", "cognitive-training", "social", "vascular" ], "population": "Leipzig AgeWell.de participants with 3T MRI before/after intervention (56 baseline, 41 follow-up; mean age 68.8)", "n_participants": 56, "age_range": "60-77 (mean 68.8)", "duration": "~28 months between scans", "primary_outcome": "hippocampal volume, entorhinal cortex thickness, free water fraction, PSMD, WMH volume, grey-matter cerebral blood flow", "outcome_measure": "linear mixed models on MRI markers", "result": "null", "effect_size": "no conclusive intervention effect on any marker; entorhinal thickness and free water declined MORE in intervention group in preregistered models but not after adjusting for baseline differences; exploratory: cerebral blood flow increased more in intervention group, associated with SBP reductions (no numeric estimates in abstract)", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "none reported", "biomarker_endpoints": "MRI atrophy and small-vessel-disease markers (null); CBF (exploratory)", "year": 2025, "publication": "Beyer F et al. Neuroimage Clin 2025;46:103796", "url": "https://pubmed.ncbi.nlm.nih.gov/40378769/", "doi": "10.1016/j.nicl.2025.103796", "pubmed_id": "40378769", "replication_status": "not-replicated", "limitations": "Very small (41 with follow-up), single site, smaller than planned; baseline imbalance.", "notes": "Consistent with US POINTER imaging ancillary (no biomarker effect of lifestyle intervention). MEASURED. Source: PubMed abstract (E-utilities efetch) loaded 2026-09-22." }, { "id": "mind-china-ongoing", "trial_name": "MIND-China (Multimodal INterventions to delay Dementia and disability in rural China)", "intervention": "multidomain lifestyle intervention (FINGER-adapted) in rural communities; intervention arm details not in the baseline paper", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular" ], "population": "rural residents >=60 years, western Shandong province, China; 5765 completed baseline assessment (mean age 70.9; 57.2% women; 40.6% illiterate)", "n_participants": 5765, "age_range": "60+ (mean 70.9)", "duration": "", "primary_outcome": "", "outcome_measure": "", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "baseline modules: brain MRI, blood biomarkers, actigraphy, cardiopulmonary coupling (sleep), audiometry, OCT", "year": 2022, "publication": "Wang Y et al. Alzheimers Dement (N Y) 2022;8(1):e12254 (baseline paper)", "url": "https://pubmed.ncbi.nlm.nih.gov/35441085/", "doi": "10.1002/trc2.12254", "pubmed_id": "35441085", "replication_status": "ongoing", "limitations": "No intervention outcome publication located in PubMed as of 2026-09-22 (search 'MIND-China[tiab]' returned baseline/cross-sectional papers only). n_participants is the baseline cohort, not necessarily the randomised sample.", "notes": "World-Wide FINGERS member; baseline dementia prevalence 5.4%. Result fields intentionally empty. Source: PubMed abstract loaded 2026-09-22." }, { "id": "finger-nl-ongoing", "trial_name": "FINGER-NL (Netherlands)", "intervention": "multidomain lifestyle intervention (FINGER-adapted), 2 years", "intervention_components": [ "diet", "exercise", "cognitive-training", "vascular", "social" ], "population": "cognitively healthy Dutch adults 60-79 with dementia prevention potential; 1008 included via Dutch Brain Research Registry campaign (13,795 registrants, 3475 eligible)", "n_participants": 1008, "age_range": "60-79", "duration": "2 years", "primary_outcome": "", "outcome_measure": "", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "", "year": 2025, "publication": "Waterink L et al. Alzheimers Dement (N Y) 2025;11(1):e70017 (recruitment paper)", "url": "https://pubmed.ncbi.nlm.nih.gov/39790861/", "doi": "10.1002/trc2.70017", "pubmed_id": "39790861", "replication_status": "ongoing", "limitations": "No primary outcome publication located as of 2026-09-22; n reflects inclusions via the registry campaign only (total enrolment may differ).", "notes": "World-Wide FINGERS member. Baseline cross-sectional diet analysis (PMID 40925079, n=1135) found no association of MIND-NL diet with global cognition. Source: PubMed abstract loaded 2026-09-22." }, { "id": "a4-2023-primary", "trial_name": "A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's)", "intervention": "solanezumab (anti-monomeric amyloid-beta antibody) up to 1600 mg IV every 4 weeks vs placebo, in cognitively unimpaired adults with elevated amyloid PET (secondary prevention setting)", "intervention_components": [ "pharmacologic" ], "population": "cognitively unimpaired persons 65-85 with global CDR 0, MMSE >=25 and elevated brain amyloid on 18F-florbetapir PET; mean age 72, ~60% women, 75% family history of dementia", "n_participants": 1169, "age_range": "65-85", "duration": "240 weeks (~4.6 years)", "primary_outcome": "change in Preclinical Alzheimer Cognitive Composite (PACC) over 240 weeks", "outcome_measure": "PACC (sum of four z scores)", "result": "null", "effect_size": "PACC change -1.43 solanezumab vs -1.13 placebo; difference -0.30 (95% CI -0.82 to 0.22)", "effect_size_type": "between-group difference in PACC change at 240 weeks", "p_value": "0.26", "cognitive_domain_affected": "none (global composite; numerically worse on solanezumab)", "biomarker_endpoints": "amyloid PET rose by 11.6 centiloids (solanezumab) vs 19.3 centiloids (placebo); ARIA-E <1% in each arm; ARIA-H 29.2% vs 32.8%", "year": 2023, "publication": "Sperling RA et al. N Engl J Med 2023;389(12):1096-1107", "url": "https://pubmed.ncbi.nlm.nih.gov/37458272/", "doi": "10.1056/NEJMoa2305032", "pubmed_id": "37458272", "replication_status": "not-replicated", "limitations": "Abstract does not enumerate limitations. Design note from the abstract: solanezumab targets monomeric (not plaque) amyloid and only partially slowed amyloid accumulation, so the trial does not test plaque removal in preclinical AD. NCT02008357.", "notes": "First completed phase 3 anti-amyloid trial in the pre-symptomatic (preclinical) setting; NULL. Funded by NIA and others. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "dian-tu-001-2021-primary", "trial_name": "DIAN-TU-001 (gantenerumab / solanezumab in dominantly inherited AD)", "intervention": "gantenerumab (subcutaneous anti-aggregated-amyloid antibody) or solanezumab (IV anti-monomeric antibody) vs placebo, 3:1 per drug arm, 4-7 years, in asymptomatic and symptomatic autosomal-dominant mutation carriers", "intervention_components": [ "pharmacologic" ], "population": "carriers of dominantly inherited AD mutations, asymptomatic and mildly symptomatic (CDR 0-1), within -15 to +10 years of estimated symptom onset; 52 gantenerumab, 52 solanezumab, 40 placebo", "n_participants": 144, "age_range": "adults 15 years before to 10 years after estimated symptom onset (ages not given in abstract)", "duration": "4-7 years", "primary_outcome": "cognitive endpoint (DIAN multivariate cognitive composite)", "outcome_measure": "DIAN-TU cognitive composite; secondary clinical, imaging and fluid biomarkers", "result": "null", "effect_size": "neither drug showed a beneficial effect on cognitive measures vs controls; solanezumab group showed greater cognitive decline on some measures; gantenerumab significantly reduced amyloid plaques, CSF total tau and p-tau181 and attenuated NfL increases", "effect_size_type": "between-group difference on cognitive composite (not significant; numeric values not in abstract)", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "gantenerumab: amyloid PET, CSF t-tau, p-tau181 reduced; NfL rise attenuated. ARIA-E 19.2% gantenerumab (3 of 11 mildly symptomatic), 2.5% placebo, 0% solanezumab", "year": 2021, "publication": "Salloway S et al. Nat Med 2021;27(7):1187-1196", "url": "https://pubmed.ncbi.nlm.nih.gov/34155411/", "doi": "10.1038/s41591-021-01369-8", "pubmed_id": "34155411", "replication_status": "not-replicated", "limitations": "Authors note the asymptomatic groups showed no cognitive decline over the trial (so slowing could not be detected) and symptomatic participants had declined before reaching target doses (doses were escalated late); small arms (n=40-52).", "notes": "Platform prevention trial in autosomal-dominant AD (NCT01760005). NULL on cognition; gantenerumab positive on biomarkers, which motivated the open-label extension (see dian-tu-gantenerumab-ole-2025). Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "dian-tu-gantenerumab-ole-2025", "trial_name": "DIAN-TU gantenerumab open-label extension", "intervention": "high-dose subcutaneous gantenerumab up to 1500 mg every 2 weeks, open-label, for up to 3 years after the double-blind DIAN-TU-001 period", "intervention_components": [ "pharmacologic" ], "population": "dominantly inherited AD mutation carriers who had completed DIAN-TU-001 and knew their mutation status; 18 sites in 8 countries; 74 recruited, 73 treated", "n_participants": 73, "age_range": "adults at risk for dominantly inherited AD (ages not given in abstract)", "duration": "3 years (stopped early after interim analysis; 13 completed 3 years)", "primary_outcome": "final analysis: 11C-PiB-PET SUVR change at 3 years (mITT n=55); prespecified interim: CDR-SB clinical decline in asymptomatic carriers vs external controls", "outcome_measure": "PiB-PET SUVR; CDR-SB time-to-decline hazard ratio", "result": "mixed", "effect_size": "interim HR for CDR-SB decline in asymptomatic carriers 0.79 (95% CI 0.47-1.32; n=53) for any gantenerumab exposure and 0.53 (95% CI 0.27-1.03; n=22) for the longest-treated group; PiB-PET SUVR change from OLE baseline to year 3: -0.71 (95% CI -0.88 to -0.53)", "effect_size_type": "hazard ratio (clinical decline vs external controls); mean change in PiB-PET SUVR", "p_value": "<0.0001 (PiB-PET SUVR); HRs not significant", "cognitive_domain_affected": "global clinical (CDR-SB) - trend only, not significant", "biomarker_endpoints": "amyloid PET SUVR -0.71 at 3 years; ARIA in 53% (39/73): microhaemorrhages 47%, oedema 30%, superficial siderosis 6%; no macrohaemorrhages or deaths", "year": 2025, "publication": "Bateman RJ et al. Lancet Neurol 2025;24(4):316-330", "url": "https://pubmed.ncbi.nlm.nih.gov/40120616/", "doi": "10.1016/S1474-4422(25)00024-9", "pubmed_id": "40120616", "replication_status": "not-replicated", "limitations": "Authors: conclusions limited by open-label design and use of external controls; study stopped early by sponsor (no regulatory path for gantenerumab) - 47 of 73 stopped dosing for that reason and only 13 completed 3 years; small numbers (HR estimates on n=53 and n=22).", "notes": "Widely cited as the first signal that long-term full amyloid removal may delay symptom onset in pre-symptomatic carriers (HR 0.53 in longest-treated), but not statistically significant. OLE registered NCT06424236; parent NCT01760005. Marked 'mixed' (significant biomarker effect, non-significant clinical trend). Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "api-adad-colombia-crenezumab-2026", "trial_name": "API ADAD Colombia Trial (crenezumab in PSEN1 E280A carriers)", "intervention": "crenezumab (anti-amyloid-beta antibody) subcutaneous 300 mg then 720 mg every 2 weeks, later optional 60 mg/kg IV every 4 weeks, vs placebo, for 5-8 years in cognitively unimpaired mutation carriers; mutation non-carriers received placebo as a masked kindred control", "intervention_components": [ "pharmacologic" ], "population": "cognitively unimpaired PSEN1 Glu280Ala (E280A) kindred members aged 30-60 in Medellin, Colombia; 85 crenezumab carriers, 84 placebo carriers, 83 placebo non-carriers; 63% women", "n_participants": 252, "age_range": "30-60", "duration": "5-8 years (common close); enrolled Dec 2013-Feb 2017, final data March 2022", "primary_outcome": "dual primary: annualised rate of change in API preclinical ADAD composite total score and in FCSRT Cueing Index", "outcome_measure": "API ADAD composite; Free and Cued Selective Reminding Test-Cueing Index", "result": "null", "effect_size": "API ADAD composite annualised change -1.10 (SE 0.29) crenezumab vs -1.43 (0.29) placebo, difference 0.33 (95% CI -0.48 to 1.13); FCSRT-CI -0.03 vs -0.04, difference 0.01 (95% CI 0.00 to 0.02)", "effect_size_type": "between-group difference in annualised rate of change", "p_value": "0.43 (composite); 0.16 (FCSRT-CI)", "cognitive_domain_affected": "none", "biomarker_endpoints": "secondary/exploratory: no significant effect on amyloid plaque removal or other biomarker outcomes; serious adverse events 27% vs 25%; no deaths", "year": 2026, "publication": "Tariot PN et al. Lancet Neurol 2026;25(2):147-159", "url": "https://pubmed.ncbi.nlm.nih.gov/41579901/", "doi": "10.1016/S1474-4422(25)00426-0", "pubmed_id": "41579901", "replication_status": "not-replicated", "limitations": "Single-centre, single-kindred phase 2 with 169 mutation carriers; crenezumab did not remove fibrillar amyloid, so the trial does not test plaque clearance; authors conclude robust fibrillar amyloid removal appears necessary for clinical efficacy.", "notes": "Longest anti-amyloid prevention trial to date (5-8 years) in autosomal-dominant AD; NCT01998841; funded by NIA, Banner, Genentech/Roche. NULL. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "early-atabecestat-2021-primary", "trial_name": "EARLY (atabecestat in preclinical AD)", "intervention": "atabecestat (oral BACE inhibitor) 5 mg or 25 mg daily vs placebo (1:1:1) in amyloid-positive cognitively normal adults", "intervention_components": [ "pharmacologic" ], "population": "amyloid-positive, cognitively normal (CDR 0) adults aged 60-85 at 143 centres in 14 countries; 557 randomized of 4464 screened (34% of planned 1650); 61% women; mean age 70.4", "n_participants": 557, "age_range": "60-85", "duration": "planned 4.5 years; dosing stopped May 2018 (trial ran Nov 2015-Dec 2018) with 6 months off-treatment follow-up", "primary_outcome": "change from baseline in Preclinical Alzheimer Cognitive Composite (PACC)", "outcome_measure": "PACC; secondary Cognitive Function Index and RBANS", "result": "harmful", "effect_size": "atabecestat 25 mg vs placebo: PACC least-squares mean difference -1.09 (95% CI -1.66 to -0.53) at month 6 and -1.62 (95% CI -2.49 to -0.76) at month 12; RBANS -3.70 (95% CI -5.76 to -1.63) at month 3; worsening reversed after 6 months off treatment", "effect_size_type": "between-group least-squares mean difference in PACC change", "p_value": "<0.001", "cognitive_domain_affected": "global composite worse (dose-related), plus neuropsychiatric adverse events", "biomarker_endpoints": "biomarker outcomes reported in paper (not detailed in abstract)", "year": 2021, "publication": "Sperling R et al. JAMA Neurol 2021;78(3):293-301", "url": "https://pubmed.ncbi.nlm.nih.gov/33464300/", "doi": "10.1001/jamaneurol.2020.4857", "pubmed_id": "33464300", "replication_status": "replicated", "limitations": "Truncated trial: enrollment stopped at 34% of plan and treatment stopped early for hepatic adverse events, so the planned efficacy question could not be answered; follow-up off-treatment limited to 6 months.", "notes": "HARMFUL: dose-related cognitive worsening as early as 3 months, consistent with other BACE-inhibitor trials (umibecestat Generation, verubecestat). NCT02569398. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "tommorrow-2021-primary", "trial_name": "TOMMORROW (pioglitazone delay-of-onset)", "intervention": "low-dose pioglitazone 0.8 mg/day sustained-release vs placebo in cognitively healthy adults classed as high-risk by a TOMM40/APOE/age biomarker risk algorithm (BRAA); low-risk participants received placebo", "intervention_components": [ "pharmacologic" ], "population": "cognitively healthy community-living adults 65-83 at 57 clinics in Australia, Germany, Switzerland, UK and USA; 3494 enrolled (3061 high risk, 433 low risk); 1545 randomized to pioglitazone, 1516 to placebo", "n_participants": 3494, "age_range": "65-83", "duration": "event-driven (planned to 202 MCI events); enrolled Aug 2013-Dec 2015, terminated Jan 2018 for futility", "primary_outcome": "time to onset of MCI due to AD (high-risk pioglitazone vs high-risk placebo); co-primary: high-risk vs low-risk placebo (BRAA qualification)", "outcome_measure": "adjudicated MCI due to AD", "result": "null", "effect_size": "MCI in 39/1430 (2.7%) pioglitazone vs 46/1406 (3.3%) placebo, HR 0.80 (99% CI 0.45-1.40); BRAA high vs low risk HR 3.26 (99% CI 0.85-12.45, p=0.023)", "effect_size_type": "hazard ratio", "p_value": "0.307", "cognitive_domain_affected": "none", "biomarker_endpoints": "genetic risk algorithm (TOMM40 '523 + APOE + age) showed 3x enrichment of events but missed prespecified significance (p=0.01 threshold); deaths 7 (0.5%) vs 21 (1.4%)", "year": 2021, "publication": "Burns DK et al. Lancet Neurol 2021;20(7):537-547", "url": "https://pubmed.ncbi.nlm.nih.gov/34146512/", "doi": "10.1016/S1474-4422(21)00043-0", "pubmed_id": "34146512", "replication_status": "not-replicated", "limitations": "Authors: study terminated after failing the non-futility threshold, so findings are exploratory only; 1104 participants discontinued treatment; low event rate (3.3% in placebo); BRAA analyses limited to White non-Hispanic participants.", "notes": "Largest pharmacological delay-of-onset prevention trial of the 2010s (Takeda/Zinfandel); NULL. NCT01931566. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "api-generation-umibecestat-2024", "trial_name": "API Generation Studies (umibecestat/CNP520 in APOE4 carriers)", "intervention": "umibecestat (oral BACE1 inhibitor) 50 mg or 15 mg daily vs placebo in cognitively unimpaired APOE e4 homozygotes, and heterozygotes with elevated brain amyloid; studies terminated early after ~7 months average exposure", "intervention_components": [ "pharmacologic" ], "population": "cognitively unimpaired 60-75 year-old APOE e4 homozygotes and heterozygotes with elevated amyloid", "n_participants": 1556, "age_range": "60-75", "duration": "7 months treatment on average (terminated early); median 4 (IQR 3-6) months washout follow-up", "primary_outcome": "planned: time to diagnosis of MCI/dementia due to AD and API preclinical composite; this report: reversibility of cognitive worsening after washout", "outcome_measure": "RBANS, API Preclinical Composite Cognitive test, CDR-SB", "result": "harmful", "effect_size": "small, non-progressive but statistically significant decline vs placebo on RBANS and API Preclinical Composite (not CDR-SB) during treatment; RBANS differences no longer significant at end of washout follow-up (numeric effect sizes not in abstract)", "effect_size_type": "between-group difference in cognitive test scores (values not in abstract)", "p_value": "", "cognitive_domain_affected": "global cognition worse on treatment (reversible)", "biomarker_endpoints": "not reported in abstract; anonymized data, images and samples available on request", "year": 2024, "publication": "Tariot PN et al. Alzheimers Dement 2024;20(11):7745-7761", "url": "https://pubmed.ncbi.nlm.nih.gov/39320017/", "doi": "10.1002/alz.14237", "pubmed_id": "39320017", "replication_status": "replicated", "limitations": "Studies terminated early (July 2019) so no efficacy readout; reversibility assessed over a median of only 4 months off drug; abstract reports no effect sizes.", "notes": "HARMFUL (symptomatic, reversible cognitive side effect of high-dose BACE inhibition), replicating the EARLY/atabecestat pattern. Registry IDs not stated in abstract, so none recorded. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "ahead-3-45-ongoing-protocol", "trial_name": "AHEAD 3-45 (lecanemab in preclinical AD)", "intervention": "lecanemab (BAN2401) IV, dose regimens tailored to baseline amyloid: A3 (intermediate amyloid ~20-40 centiloids, phase 2, PET endpoints) and A45 (elevated amyloid >40 centiloids, phase 3, cognitive composite primary) vs placebo, 4-year treatment", "intervention_components": [ "pharmacologic" ], "population": "cognitively unimpaired adults 55-80 with intermediate or elevated brain amyloid; plasma Abeta42/40 used to screen before PET; recruitment via TRC-PAD, ADNeT and J-TRC registries", "n_participants": 1400, "age_range": "55-80", "duration": "4 years treatment", "primary_outcome": "A45: change in cognitive composite (PACC5); A3: amyloid PET change", "outcome_measure": "PACC5 cognitive composite; amyloid and tau PET", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "planned: amyloid PET, tau PET, plasma biomarkers", "year": 2023, "publication": "Rafii MS et al. Alzheimers Dement 2023;19(4):1227-1233 (design paper; epub Aug 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35971310/", "doi": "10.1002/alz.12748", "pubmed_id": "35971310", "replication_status": "ongoing", "limitations": "Design paper only; no results. ClinicalTrials.gov NCT04468659: phase 3, ACTIVE_NOT_RECRUITING, enrollment 1400 (ESTIMATED), start 2020-07-14, primary completion 2028-12-21 (registry loaded 2026-09-27).", "notes": "Public-private ACTC/NIA/Eisai secondary-prevention trial launched 14 July 2020; first prevention trial to use plasma biomarker pre-screening. n_participants is the registry's estimated enrollment. Result fields intentionally empty (ongoing). Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "trailblazer-alz-3-ongoing-baseline-2025", "trial_name": "TRAILBLAZER-ALZ 3 (donanemab in preclinical AD)", "intervention": "donanemab IV monthly x9 infusions vs placebo, then clinical assessments every 6 months (decentralized design, plasma p-tau217 eligibility)", "intervention_components": [ "pharmacologic" ], "population": "adults 55-80 in the US and Japan with AD pathology detected by plasma p-tau217; 63,124 screened, 2196 enrolled (CDR-Global 0 n=1202; 0.5 n=664); mean baseline amyloid 63.2 centiloids (CDR 0) and 70.7 (CDR 0.5)", "n_participants": 2196, "age_range": "55-80", "duration": "9 monthly infusions then event-driven follow-up", "primary_outcome": "time to clinical progression (time-to-event)", "outcome_measure": "clinical progression (CDR-based) - time to event", "result": "", "effect_size": "", "effect_size_type": "", "p_value": "", "cognitive_domain_affected": "", "biomarker_endpoints": "baseline: elevated global tau PET (SUVR >=1.10) in 15.1% of CDR 0 and 26.3% of CDR 0.5 participants; PET substudy planned", "year": 2025, "publication": "Yaari R et al. Alzheimers Dement 2025;21(9):e70662 (screening and baseline paper)", "url": "https://pubmed.ncbi.nlm.nih.gov/40955720/", "doi": "10.1002/alz.70662", "pubmed_id": "40955720", "replication_status": "ongoing", "limitations": "Baseline/screening paper only; no efficacy results. Plasma p-tau217 eligibility rates differed by age, race and ethnicity (authors).", "notes": "NCT05026866. Companion to AHEAD 3-45 in the pre-symptomatic setting. Result fields intentionally empty (ongoing). Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "rewind-dulaglutide-2020-cognition", "trial_name": "REWIND (dulaglutide; exploratory cognitive outcome)", "intervention": "dulaglutide 1.5 mg subcutaneous weekly (GLP-1 receptor agonist) vs placebo; cognition assessed with MoCA and DSST at baseline and follow-up", "intervention_components": [ "pharmacologic" ], "population": "adults >=50 with type 2 diabetes and additional cardiovascular risk factors at 371 sites in 24 countries; 9901 randomized (4949 dulaglutide, 4952 placebo); 8828 with baseline plus follow-up cognitive scores", "n_participants": 9901, "age_range": ">=50", "duration": "median 5.4 years (IQR 5.1-5.9)", "primary_outcome": "exploratory: first occurrence of substantive cognitive impairment (MoCA or DSST score >=1.5 SD below country baseline mean)", "outcome_measure": "MoCA and DSST threshold event", "result": "mixed", "effect_size": "4.05 vs 4.35 events per 100 patient-years; HR 0.93 (95% CI 0.85-1.02); after post-hoc adjustment for individual standardised baseline scores HR 0.86 (95% CI 0.79-0.95)", "effect_size_type": "hazard ratio", "p_value": "0.11 (unadjusted); 0.0018 (post-hoc adjusted)", "cognitive_domain_affected": "global (MoCA) and processing speed (DSST) composite event", "biomarker_endpoints": "none", "year": 2020, "publication": "Cukierman-Yaffe T et al. Lancet Neurol 2020;19(7):582-590", "url": "https://pubmed.ncbi.nlm.nih.gov/32562683/", "doi": "10.1016/S1474-4422(20)30173-3", "pubmed_id": "32562683", "replication_status": "not-replicated", "limitations": "Exploratory analysis of a cardiovascular outcomes trial (cognition was not a primary endpoint); the prespecified unadjusted comparison was not significant and benefit appeared only after post-hoc adjustment; diabetes population only.", "notes": "First large randomized GLP-1 RA signal on cognition; 'mixed' because unadjusted primary null, post-hoc adjusted positive. NCT01394952. Lilly-funded. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "carolina-cognition-2021", "trial_name": "CAROLINA-COGNITION (linagliptin vs glimepiride)", "intervention": "linagliptin 5 mg (DPP-4 inhibitor) vs glimepiride (sulfonylurea), double-blind active-controlled, in type 2 diabetes", "intervention_components": [ "pharmacologic" ], "population": "adults 40-85 with relatively early type 2 diabetes (HbA1c 6.5-8.5%) at elevated cardiovascular risk, baseline MMSE >=24; 3163 of the 6033 CAROLINA participants (38% female, mean age 64, diabetes duration 7.6 years)", "n_participants": 3163, "age_range": "40-85", "duration": "median 6.1 years", "primary_outcome": "accelerated cognitive decline at end of follow-up (regression-based index score <=16th percentile on MMSE or an attention/executive composite)", "outcome_measure": "MMSE; attention and executive function composite", "result": "null", "effect_size": "accelerated cognitive decline in 27.8% (449/1618) linagliptin vs 27.6% (426/1545) glimepiride, OR 1.01 (95% CI 0.86-1.18); at week 160 OR 1.07 (95% CI 0.91-1.25); no subgroup differences", "effect_size_type": "odds ratio", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2021, "publication": "Biessels GJ et al. Diabetologia 2021;64(6):1235-1245", "url": "https://pubmed.ncbi.nlm.nih.gov/33559704/", "doi": "10.1007/s00125-021-05393-8", "pubmed_id": "33559704", "replication_status": "replicated", "limitations": "Active-comparator design (no placebo) so neither drug's effect vs no treatment is estimable; cognition substudy of a cardiovascular safety trial; relatively early diabetes with high baseline MMSE.", "notes": "Replicates the null CARMELINA cognition result for linagliptin. NCT01243424. Boehringer Ingelheim-funded. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "infinity-2019-primary", "trial_name": "INFINITY (intensive vs standard ambulatory BP control)", "intervention": "antihypertensive treatment to a 24-hour ambulatory systolic BP goal of <=130 mmHg (intensive) vs <=145 mmHg (standard) for 3 years", "intervention_components": [ "pharmacologic", "vascular" ], "population": "adults >=75 with systolic hypertension and MRI white-matter hyperintensity lesions; mean age 80.5, 54% women; mean 24-h systolic BP 149 mmHg at baseline", "n_participants": 199, "age_range": ">=75", "duration": "3 years", "primary_outcome": "co-primary: change in mobility (gait speed) and accrual of white-matter hyperintensity volume at 3 years; cognitive function (executive processing) secondary", "outcome_measure": "gait speed; WMH volume on MRI; executive function tests", "result": "mixed", "effect_size": "achieved 24-h SBP 127.7 vs 144.0 mmHg (difference 16.3); WMH volume accrual 0.29% intensive vs 0.48% standard; gait-speed change 0.40 vs 0.42 s (no difference); cognitive outcomes not different; major adverse cardiovascular events 4 vs 17", "effect_size_type": "between-group difference in 3-year change (WMH %, gait speed); event counts", "p_value": "0.03 (WMH); 0.91 (gait); 0.01 (MACE); cognition not significant (value not in abstract)", "cognitive_domain_affected": "none (executive processing not different)", "biomarker_endpoints": "white-matter hyperintensity accrual reduced with intensive control", "year": 2019, "publication": "White WB et al. Circulation 2019;140(20):1626-1635", "url": "https://pubmed.ncbi.nlm.nih.gov/31607143/", "doi": "10.1161/CIRCULATIONAHA.119.041603", "pubmed_id": "31607143", "replication_status": "replicated", "limitations": "Small (199 randomized) single-centre trial with a 3-year horizon; cognition was a secondary outcome; authors note benefit on function may require periods >3 years.", "notes": "Cardiovascular/BP trial with imaging + cognitive endpoints in the very old; consistent with the SPRINT MIND MRI substudy (WMH benefit without cognitive difference). NCT01650402. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "enlighten-2019-primary", "trial_name": "ENLIGHTEN (aerobic exercise and DASH diet)", "intervention": "2x2 factorial: 6 months supervised aerobic exercise and/or DASH diet nutritional counselling vs health education control", "intervention_components": [ "exercise", "diet" ], "population": "160 sedentary men and women >55 with cognitive impairment no dementia (CIND) and cardiovascular risk factors", "n_participants": 160, "age_range": ">55", "duration": "6 months", "primary_outcome": "prespecified composite of executive function", "outcome_measure": "executive function composite; secondary language/verbal fluency, memory, modified CDR", "result": "mixed", "effect_size": "aerobic exercise d=0.32 (p=0.046); DASH diet d=0.30 (p=0.059, not significant); combined exercise+DASH vs health education d=0.40 (p=0.012); no improvement in memory or language/verbal fluency", "effect_size_type": "Cohen's d for executive function composite", "p_value": "0.046 (exercise main effect); 0.012 (combined arm vs control)", "cognitive_domain_affected": "executive function only", "biomarker_endpoints": "greater aerobic fitness, lower CVD risk and lower sodium intake associated with executive improvement (biomarker paper separate)", "year": 2019, "publication": "Blumenthal JA et al. Neurology 2019;92(3):e212-e223 (epub 2018-12-19)", "url": "https://pubmed.ncbi.nlm.nih.gov/30568005/", "doi": "10.1212/WNL.0000000000006784", "pubmed_id": "30568005", "replication_status": "not-replicated", "limitations": "Authors describe findings as preliminary: small (n=160), 6-month intervention, single site; participants already had CIND (so this is delay-of-progression rather than primary prevention); DASH main effect not significant.", "notes": "Class I evidence per journal that aerobic exercise (not DASH) improves executive function in CIND. 'Mixed': positive for exercise on the primary domain only. NCT01573546. A 1-year follow-up paper exists (J Am Geriatr Soc 2019, PMID 31755550) not loaded here. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "i-conect-2024-primary", "trial_name": "I-CONECT (Internet-based Conversational Engagement)", "intervention": "semi-structured cognitively stimulating video-chat conversations with trained interviewers 4x/week for 6 months (induction) then 2x/week for 6 months (maintenance) vs control; both arms received weekly 10-minute telephone check-ins", "intervention_components": [ "social", "cognitive-training" ], "population": "socially isolated adults 75+ with normal cognition or MCI, multisite US trial (186 randomized)", "n_participants": 186, "age_range": "75+", "duration": "12 months (6 induction + 6 maintenance)", "primary_outcome": "global cognition (MoCA) after the 6-month induction period", "outcome_measure": "MoCA; secondary semantic fluency, Craft Story recall, resting-state fMRI", "result": "positive", "effect_size": "MoCA +1.75 points vs control after induction; semantic fluency +2.56 points in normal-cognition subgroup; Craft Story immediate recall +2.19 points in MCI subgroup at end of maintenance; increased dorsal attention network connectivity on rs-fMRI", "effect_size_type": "between-group difference in test points", "p_value": "0.03 (MoCA primary); 0.03 (semantic fluency); 0.04 (Craft Story); 0.02 (fMRI)", "cognitive_domain_affected": "global cognition; language-based executive function (normal cognition); memory encoding (MCI)", "biomarker_endpoints": "rs-fMRI dorsal attention network connectivity increased (limited sample)", "year": 2024, "publication": "Dodge HH et al. Gerontologist 2024;64(4):gnad147", "url": "https://pubmed.ncbi.nlm.nih.gov/37935416/", "doi": "10.1093/geront/gnad147", "pubmed_id": "37935416", "replication_status": "not-replicated", "limitations": "Authors note COVID-19-related protocol modifications; small sample (186) with subgroup findings; fMRI sample size limited; emotional well-being improved in both arms.", "notes": "Social-engagement RCT with a cognitive primary endpoint; POSITIVE on MoCA. NCT02871921. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "vital-cog-omega3-2022", "trial_name": "VITAL-Cog / CTSC-Cog (marine omega-3 and cognition)", "intervention": "marine n-3 fatty acids 1 g/day (840 mg EPA+DHA) vs placebo within the 2x2 VITAL trial (vitamin D3 2000 IU/day the other factor)", "intervention_components": [ "supplement" ], "population": "healthy community-dwelling US adults 60+ (mean age 70.9) free of CVD and cancer: 3424 assessed by telephone (VITAL-Cog, 2.8 years) and 794 in person (CTSC-Cog, 2.0 years)", "n_participants": 4218, "age_range": "60+", "duration": "2.8 years (telephone) / 2.0 years (in person)", "primary_outcome": "change in global cognitive composite score (mean of test z scores) over two assessments", "outcome_measure": "global composite of 8 (telephone) or 9 (in-person) neuropsychological tests", "result": "null", "effect_size": "annual rate of cognitive change, n-3 vs placebo: -0.01 SU (95% CI -0.02 to 0.003) VITAL-Cog and -0.002 (95% CI -0.04 to 0.03) CTSC-Cog; pooled -0.01 (95% CI -0.02 to 0.003)", "effect_size_type": "between-group difference in annual change of global composite (standard units)", "p_value": "0.15", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2022, "publication": "Kang JH et al. Alzheimers Dement (N Y) 2022;8(1):e12288", "url": "https://pubmed.ncbi.nlm.nih.gov/35415212/", "doi": "10.1002/trc2.12288", "pubmed_id": "35415212", "replication_status": "replicated", "limitations": "Follow-up only 2-3 years; healthy volunteers; most cognition assessed by telephone; ancillary studies of a CVD/cancer prevention trial.", "notes": "Supplement NULL (consistent with DO-HEALTH, MAPT omega-3). Parent trial NCT01169259; VITAL-Cog NCT01669915. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "vital-cog-vitamin-d-2021", "trial_name": "VITAL-Cog / CTSC-Cog (vitamin D3 and cognition)", "intervention": "vitamin D3 2000 IU/day (cholecalciferol) vs placebo within the 2x2 VITAL trial", "intervention_components": [ "supplement" ], "population": "US adults 60+ (mean 70.9) free of CVD and cancer: 3424 telephone-assessed (2.8 years) and 794 in-person (2.0 years); 19% Black participants", "n_participants": 4218, "age_range": "60+", "duration": "2.8 years (telephone) / 2.0 years (in person)", "primary_outcome": "decline in global composite cognitive score over two assessments (prespecified)", "outcome_measure": "global composite of 8-9 neuropsychological tests", "result": "null", "effect_size": "pooled mean difference in annual rate of decline, vitamin D3 vs placebo: 0.01 (95% CI -0.01 to 0.02); no interaction with baseline 25(OH)D (p-interaction 0.84); interaction with self-reported race p=0.01 - Black participants MD 0.04 (95% CI 0.01 to 0.08)", "effect_size_type": "between-group difference in annual change of global composite (standard units)", "p_value": "0.39", "cognitive_domain_affected": "none overall; possible benefit in Black participants (subgroup)", "biomarker_endpoints": "baseline 25-hydroxyvitamin D did not modify effect", "year": 2021, "publication": "Kang JH et al. Sci Rep 2021;11(1):23253", "url": "https://pubmed.ncbi.nlm.nih.gov/34853363/", "doi": "10.1038/s41598-021-02485-8", "pubmed_id": "34853363", "replication_status": "replicated", "limitations": "2-3 year follow-up; authors state the subgroup result in Black participants needs confirmation; telephone testing for the majority.", "notes": "Supplement NULL. NCT01169259 (VITAL), NCT01669915 (VITAL-Cog). Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "do-health-2020-primary", "trial_name": "DO-HEALTH", "intervention": "2x2x2 factorial: vitamin D3 2000 IU/day, omega-3 1 g/day, and/or a home strength-training exercise programme vs placebo, 3 years", "intervention_components": [ "supplement", "exercise" ], "population": "2157 generally healthy adults >=70 (mean 74.9; 61.7% women) in 5 European countries with no major health events in prior 5 years, sufficient mobility and good cognitive status", "n_participants": 2157, "age_range": ">=70", "duration": "3 years (median follow-up 2.99 years)", "primary_outcome": "6 primary outcomes including change in Montreal Cognitive Assessment (MoCA) at 3 years", "outcome_measure": "MoCA (plus systolic/diastolic BP, SPPB, non-vertebral fractures, infections)", "result": "null", "effect_size": "no statistically significant benefit of any intervention alone or in combination on any of the 6 endpoints including MoCA (99% CIs; P<.01 required)", "effect_size_type": "between-group difference in 3-year change in MoCA (values not in abstract)", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "none", "year": 2020, "publication": "Bischoff-Ferrari HA et al. JAMA 2020;324(18):1855-1868", "url": "https://pubmed.ncbi.nlm.nih.gov/33170239/", "doi": "10.1001/jama.2020.16909", "pubmed_id": "33170239", "replication_status": "replicated", "limitations": "Healthy, high-functioning cohort with good baseline cognition (ceiling effects); MoCA as the only cognitive measure; 3-year horizon; 88% completed.", "notes": "Multifactorial supplement/exercise prevention trial - NULL on cognition. NCT01745263. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "keeps-continuation-2024", "trial_name": "KEEPS Continuation (long-term cognitive follow-up of menopausal hormone therapy)", "intervention": "4 years of oral conjugated equine estrogens 0.45 mg/d or transdermal estradiol 50 ug/d (each with cyclic micronized progesterone) vs placebo in the KEEPS trial (2005-2008), re-assessed ~10 years after trial completion (2017-2022)", "intervention_components": [ "pharmacologic" ], "population": "recently postmenopausal women (within 3 years of final menstrual period at randomization); 299 of 727 original participants enrolled at 7 of 9 sites, 275 with cognitive data at both time points", "n_participants": 275, "age_range": "recently postmenopausal at randomization (ages not given in abstract)", "duration": "4-year treatment + ~10-year post-trial follow-up (~14 years from randomization)", "primary_outcome": "cognitive performance (4 cognitive factor scores and global score) at ~10 years after trial end by original randomization arm", "outcome_measure": "KEEPS-Cog test battery (4 factors + global); latent growth models", "result": "null", "effect_size": "mHT allocation had no significant effect on cognitive slopes during KEEPS or across all years of follow-up in any domain; cross-sectional performance similar in oCEE, tE2 and placebo groups", "effect_size_type": "latent growth model slope differences (values not in abstract)", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "neuroimaging reported in companion papers", "year": 2024, "publication": "Gleason CE et al. PLoS Med 2024;21(11):e1004435", "url": "https://pubmed.ncbi.nlm.nih.gov/39570992/", "doi": "10.1371/journal.pmed.1004435", "pubmed_id": "39570992", "replication_status": "replicated", "limitations": "Observational follow-up of 41% of the original randomized cohort (authors report similar baseline characteristics for returners vs non-returners); 7 of 9 sites; healthy population.", "notes": "Long-term follow-up of a hormone-therapy prevention RCT: no cognitive harm or benefit (contrast with WHIMS harm in older women). NCT00154180. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "intrepad-2019-primary", "trial_name": "INTREPAD (naproxen in presymptomatic AD)", "intervention": "naproxen sodium 220 mg twice daily vs placebo for 2 years", "intervention_components": [ "pharmacologic" ], "population": "195 cognitively intact older adults (mean age 63) with a family history of AD, carefully screened to exclude cognitive disorder; modified ITT 160", "n_participants": 195, "age_range": "mean 63", "duration": "2 years", "primary_outcome": "rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS)", "outcome_measure": "APS composite (imaging, CSF in ~50%, cognitive, neurosensory measures)", "result": "null", "effect_size": "APS rose 0.102 points/year overall (SE 0.014); treatment-related difference 0.019 points/year; rate ratio 1.16 (95% CI 0.64-1.96), excluding a naproxen benefit larger than 36%; clear excess of adverse events on naproxen", "effect_size_type": "rate ratio of APS progression", "p_value": "", "cognitive_domain_affected": "none", "biomarker_endpoints": "no treatment effects on CSF, cognitive or neurosensory biomarker indicators", "year": 2019, "publication": "Meyer PF et al. Neurology 2019;92(18):e2070-e2080", "url": "https://pubmed.ncbi.nlm.nih.gov/30952794/", "doi": "10.1212/WNL.0000000000007232", "pubmed_id": "30952794", "replication_status": "replicated", "limitations": "Small (195 randomized, 160 in mITT); surrogate composite progression score rather than clinical onset; 2-year duration; increased adverse events.", "notes": "Class I evidence of no benefit; consistent with the null ADAPT naproxen/celecoxib result. NCT02702817. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "achieve-2025-social-isolation-secondary", "trial_name": "ACHIEVE (secondary: social isolation and loneliness)", "intervention": "best-practice hearing intervention (4 audiologist sessions, hearing aids, counselling, education) vs health-education control, 3 years", "intervention_components": [ "sensory", "social" ], "population": "977 adults 70-84 with untreated hearing loss without substantial cognitive impairment at 4 US sites (238 from ARIC, 739 de novo); mean age 76.3; mean better-ear PTA 39.4 dB", "n_participants": 977, "age_range": "70-84", "duration": "3 years", "primary_outcome": "exploratory: social isolation (Cohen Social Network Index) and loneliness (UCLA Loneliness Scale) over 3 years", "outcome_measure": "Cohen SNI (network size, diversity, embeddedness); UCLA Loneliness Scale", "result": "positive", "effect_size": "hearing intervention vs control: social network size +1.05 (95% CI 0.01-2.09), diversity +0.19 (95% CI 0.02-0.36), embeddedness +0.27 (95% CI 0.09-0.44); loneliness -0.94 (95% CI -1.78 to -0.11)", "effect_size_type": "between-group difference in 3-year change (fully adjusted mixed models)", "p_value": "", "cognitive_domain_affected": "not a cognitive outcome (social-connection mediator)", "biomarker_endpoints": "none", "year": 2025, "publication": "Reed NS et al. JAMA Intern Med 2025;185(7):797-806", "url": "https://pubmed.ncbi.nlm.nih.gov/40354063/", "doi": "10.1001/jamainternmed.2025.1140", "pubmed_id": "40354063", "replication_status": "not-replicated", "limitations": "Authors: exploratory outcomes; clinical meaningfulness of retaining ~1 additional social contact is unknown and loneliness changes were not clinically meaningful.", "notes": "Mechanistic follow-up to ACHIEVE (NCT03243422): hearing treatment modestly reduces social isolation, a Lancet-Commission risk factor. Distinct from the existing ACHIEVE primary, risk-quartile and GFAP/NfL rows. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "superbrain-2021-feasibility", "trial_name": "SUPERBRAIN (South Korea; facility- and home-based multidomain intervention)", "intervention": "24-week multidomain intervention (vascular risk management, cognitive training, social activity, physical exercise, nutrition guidance, motivational enhancement) delivered facility-based (3x/week) or home-based vs general health advice control", "intervention_components": [ "vascular", "cognitive-training", "social", "exercise", "diet" ], "population": "Korean adults 60-79 without dementia with >=1 modifiable dementia risk factor; facility-based n=51, home-based n=51, control n=50", "n_participants": 152, "age_range": "60-79", "duration": "24 weeks", "primary_outcome": "feasibility (retention, adherence, and no worse RBANS than control)", "outcome_measure": "retention, adherence; RBANS total scale index score", "result": "positive", "effect_size": "retention 88.2% (facility) and 96.1% (home); adherence 94.5% and 96.8%; RBANS total index change +5.46 (SD 7.50) facility and +5.50 (SD 8.14) home vs -0.74 (SD 11.51) control", "effect_size_type": "between-group difference in 24-week RBANS change", "p_value": "0.004 (each intervention arm vs control)", "cognitive_domain_affected": "global (RBANS total)", "biomarker_endpoints": "cortical thickness, BDNF, EEG and fMRI reported in companion papers", "year": 2021, "publication": "Moon SY et al. Aging (Albany NY) 2021;13(12):15898-15916", "url": "https://pubmed.ncbi.nlm.nih.gov/34148030/", "doi": "10.18632/aging.203213", "pubmed_id": "34148030", "replication_status": "not-replicated", "limitations": "Feasibility trial: small (152), 24 weeks, primary outcome was feasibility rather than cognition; outcome-assessor blinded only.", "notes": "Korean World-Wide FINGERS-aligned pilot that preceded the larger SUPERBRAIN-MEET programme. Registry ID not stated in abstract, so none recorded. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "exercise-prevention-dementia-48mo-2026", "trial_name": "Physical Exercise for Prevention of Dementia Study (48-month multimodal training RCT, Italy)", "intervention": "48 months of supervised moderate-to-high-intensity multimodal training (aerobic, resistance, stretching) vs usual habits", "intervention_components": [ "exercise" ], "population": "882 community-dwelling older adults classed as healthy, subjective memory complaints (SMC) or MCI; 674 in final analysis", "n_participants": 882, "age_range": "older adults (ages not given in abstract)", "duration": "48 months", "primary_outcome": "48-month change in MMSE", "outcome_measure": "MMSE; secondary 8 neuropsychological tests at 12, 24, 36, 48 months", "result": "positive", "effect_size": "healthy participants: exercise group higher MMSE than control (between-group effect p=0.008, partial eta-squared 0.007; time x group interaction partial eta-squared 0.025); SMC group between-group p=0.052 (partial eta-squared 0.004; interaction partial eta-squared 0.031); better memory, attention and reasoning in healthy and SMC exercisers", "effect_size_type": "partial eta-squared from linear mixed models", "p_value": "0.008 (healthy); 0.052 (SMC)", "cognitive_domain_affected": "global (MMSE); memory, attention, reasoning (secondary)", "biomarker_endpoints": "none", "year": 2026, "publication": "Iuliano E et al. Front Aging 2026;7:1847451", "url": "https://pubmed.ncbi.nlm.nih.gov/42639433/", "doi": "10.3389/fragi.2026.1847451", "pubmed_id": "42639433", "replication_status": "not-replicated", "limitations": "Single-blind; 24% not in final analysis (674/882); MCI subgroup too small for conclusive analysis (authors); very small effect sizes; MMSE has ceiling effects in healthy adults.", "notes": "One of the longest exercise-only prevention RCTs (4 years). NCT02236416. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." }, { "id": "digital-multidomain-fujian-2026", "trial_name": "Digital multidomain cognitive intervention in older adults at high dementia risk (Fujian, China)", "intervention": "6-month WeChat-delivered digital multidomain cognitive intervention vs control", "intervention_components": [ "cognitive-training", "social" ], "population": "166 adults >=60 with modified dementia risk score >79 at Fujian Provincial Hospital and 4 community health centres (April-December 2024); 154 (92.8%) completed", "n_participants": 166, "age_range": ">=60", "duration": "6 months", "primary_outcome": "general cognitive function (MoCA)", "outcome_measure": "MoCA; secondary memory, language, executive/attention, visuospatial, mobility, psychosocial and health-behaviour scales", "result": "positive", "effect_size": "MoCA improved vs control (t=2.106); ROCFT immediate and long-delay recall improved; UCLA loneliness reduced (Z=-2.641); no other significant differences", "effect_size_type": "between-group test statistics (point differences not in abstract)", "p_value": "0.037 (MoCA)", "cognitive_domain_affected": "global cognition; visuospatial memory", "biomarker_endpoints": "none", "year": 2026, "publication": "Yan Y et al. J Clin Psychiatry 2026;87(1):25m15860", "url": "https://pubmed.ncbi.nlm.nih.gov/41499182/", "doi": "10.4088/JCP.25m15860", "pubmed_id": "41499182", "replication_status": "not-replicated", "limitations": "Abstract does not enumerate limitations; small single-region sample (166), 6-month duration, no long-term follow-up, multiple secondary outcomes with borderline p-values.", "notes": "2026 digital-delivery prevention RCT with a cognitive primary endpoint. NCT06442943. Source: Europe PMC abstract loaded 2026-09-27 (PubMed search backend was down; Europe PMC MED record used)." } ]