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Every row of the evidence table
One row per finding: what was tested, which way the result went, and how the study was built. The answer by area, and where the studies disagree, are on the main page.
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Showing 45 of 382 rows. One row per study per exposure: a study that tested two different things appears twice, once for each.
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| Exposure | Question | Direction | Outcome measured | Design | People | Effect size, as the source reported it | Source |
|---|---|---|---|---|---|---|---|
| Alcohol Alcohol, tobacco and cannabis | Prevention |
Benefit
whyThis one reports light-to-moderate drinking as protective (HR 0.65) against non-drinking, and it flatly contradicts the Mendelian randomisation evidence. Infrequent drinkers were excluded, and non-drinkers include people who stopped for health reasons. |
Incident dementia over a median 13.7 years | cohort study | 296,715 | Low-moderate drinking HR 0.65 (95% CI 0.59-0.73) vs non-drinking |
European Journal of Epidemiology
2025 ✓ Peer-reviewed PMID 41014391 |
| Smoking Alcohol, tobacco and cannabis | Prevention |
Benefit
whyDirection is for QUITTING. Risk approached that of never-smokers and levelled off about seven years after quitting; weight gain after quitting narrowed the advantage. The authors flag residual confounding. |
Incident dementia over a median 9.9 years | cohort study | 32,802 | HR 0.84 (95% CI 0.73-0.95) for quitting during follow-up vs continuing to smoke |
Neurology
2026 ✓ Peer-reviewed PMID 42160746 |
| Birth cohort and calendar period (secular trend in dementia) All modifiable factors together | Prevention |
Benefit
whyDirection is for later birth cohort: each successive cohort had a significantly lower incident dementia rate, independent of sex, education and age. |
Incident dementia rate by decade of birth (1902-1941) | cohort study | 3,010 | Compared to the earliest birth cohort (1902-1911), each subsequent cohort had a significantly lower incident dementia rate (1912-1921: incidence rate ratio [IRR] = 0.655, 95% confidence interval [95% CI] = 0.477-0.899; 1922-1931: IRR = 0.387, 95% CI = 0.265-0.564; 1932-1941: IRR = 0.233, 95% CI = 0.121-0.449) |
The Journals of Gerontology: Series A (Biological Sciences and Medical Sciences)
2019 ✓ Peer-reviewed PMID 30312371 |
| Birth cohort and calendar period (secular trend in dementia) All modifiable factors together | Prevention |
Benefit
whyDirection is for later calendar epoch: incidence fell 44% from the first to the fourth epoch, but only among people with at least a high school diploma. The authors could not fully explain the decline. |
5-year incidence of dementia across four epochs (late 1970s to early 2010s) | cohort study | 5,205 | The 5-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88) |
New England Journal of Medicine
2016 ✓ Peer-reviewed PMID 26863354 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Prevention |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The estimated age at plasma %p-tau217 positivity predicted age at symptom onset (adjusted R2 0.337-0.612) with a median absolute error of 3.0-3.7 years, which the authors call acceptable for trials but not yet for individual clinical use. |
Predicted age at onset of Alzheimer's symptoms from plasma %p-tau217 clock models | cohort study | 603 | The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R2 of 0.337-0.612) with a median absolute error of 3.0-3.7 years |
Nature medicine
2026 ✓ Peer-reviewed PMID 41714746 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Prevention |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Combined plasma %p-tau217 and Aβ42/40 detected abnormal CSF amyloid status (AUC 0.949) and each predicted rising amyloid PET over time in people who started below the positivity threshold, replicated in two further cohorts; p-tau231 and GFAP added no clear independent value. |
Prediction of subsequent brain amyloid accumulation (PET/CSF) in cognitively unimpaired people with subthreshold amyloid | cohort study | 983 | a combination of plasma %p-tau217 and Aβ42/40 showed better performance (area under the curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers ... longitudinal Aβ-PET (%p-tau217: β = 0.67; 95% CI, 0.48-0.87; Aβ42/40: β = -0.33; 95% CI, -0.51 to -0.15; %p-tau217 × Aβ42/40: β = -0.31; 95% CI, -0.44 to -0.18; P < .001) |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 39068669 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Among p-tau217-positive patients, a positive eMTBR-tau243 identified clinically established Alzheimer's disease with 81% accuracy and predicted faster cognitive decline and tau accumulation. |
Classification of established Alzheimer's disease by plasma eMTBR-tau243 among %p-tau217-positive patients | cohort study | 572 | 194 (55%) of 350 %p-tau217-positive patients were also positive for eMTBR-tau243, with an accuracy of 81% (95% CI 76-84), PPV 84% (95% CI 78-88), negative predictive value (NPV) 77% (95% CI 68-82), and sensitivity 82% (95% CI 76-87) for established Alzheimer's disease, in cross-sectional analyses |
The Lancet. Neurology
2026 ✓ Peer-reviewed PMID 41864233 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. All p-tau217 tests detected abnormal amyloid PET (AUC 0.91-0.96) and tau PET (0.94-0.97); the mass-spectrometry %p-tau217 ratio was best (accuracy 0.93 versus 0.83-0.88 for immunoassays) and is proposed as a stand-alone confirmatory test, with immunoassays better suited to triage. |
Accuracy of five plasma p-tau217 tests for amyloid PET and tau PET status, benchmarked against CSF tests | cohort study | 998 | All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET [area under the curve (AUC) range: 0.91-0.96] and tau-PET (AUC range: 0.94-0.97) ... For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 0.91 (immunoassays: 0.84-0.87) and a specificity of 0.94 (immunoassays: 0.85-0.89) |
Brain
2025 ✓ Peer-reviewed PMID 39468767 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The ALZpath plasma p-tau217 immunoassay reached AUC 0.92-0.96 for amyloid and 0.93-0.97 for tau across three cohorts, comparable with CSF, and a three-range cut-off cut confirmatory testing by about 80%. |
Accuracy for abnormal amyloid and tau pathology (PET or CSF) and longitudinal change | cohort study | 786 | High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80% |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 38252443 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 identified amyloid positivity with AUC 0.94; a two-cut-point rule sent only 17% for CSF or PET (sensitivity 0.94, specificity 0.86), and among amyloid-positive people it identified high tau load (AUC 0.92), potentially avoiding 56.9% of tau-PET scans. |
Identification of amyloid positivity and of high tau-PET load (to select candidates for anti-amyloid antibodies) | cohort study | 912 | plasma p-tau217 was most strongly associated with Aβ positivity (test-set area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI, 0.90-0.97) ... This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95) ... At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aβ-positive participants |
JAMA Neurology
2024 ✓ Peer-reviewed PMID 38048096 |
| Blood biomarker test (p-tau217 / amyloid ratio) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. A blood model of p-tau217, age and APOE ε4 (AUC 89.3% development, 94.3% validation) used to triage patients gave 88-92% overall accuracy while cutting confirmatory CSF tests by 61-86%. |
Accuracy for amyloid PET status and reduction in confirmatory CSF tests with a two-step plasma p-tau217 workflow | cohort study | 348 | Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively |
Nature Aging
2023 ✓ Peer-reviewed PMID 37653254 |
| Blood biomarkers (GFAP, NfL, p-tau181) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for disclosing the blood panel during multidisciplinary meetings: median diagnostic confidence rose from 80% to 90%, though the suspected etiology changed in only 5% of patients and the syndrome diagnosis in 1%. Against CSF/PET, high- and low-probability results identified 76% of amyloid positives and 85% of negatives. |
Change in clinician diagnostic confidence and in syndrome or etiological diagnosis after disclosure of a plasma biomarker panel (p-tau181, GFAP, NfL) | cohort study | 450 | Median (IQR) diagnostic confidence in the total cohort increased from 80% (70%-90%) to 90% (70%-90%) after BBM disclosure (P < .001), increasing in 207 patients (46%), unchanged in 175 patients (39%), and decreasing in 68 patients (15%). Following BBM disclosure, syndrome diagnoses were revised in 6 patients (1%) and primary etiology was revealed in 23 patients (5%) |
JAMA Network Open
2026 ✓ Peer-reviewed PMID 42593792 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Prevention |
Benefit
whyDirection is for the blood test's prognostic performance: plasma p-tau217 predicted cognitive decline and progression to MCI as well as tau PET (R2 0.33 vs 0.34; HR 1.57 vs 1.61), and using the blood test first cut the number needed to screen for a trial by 94%. A prognostic-performance result, not a health outcome. |
Prediction of future cognitive decline and progression to MCI: plasma p-tau217 head-to-head with tau PET | cohort study | 1,474 | plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48-1.76) versus HRplasma = 1.57 (1.43-1.72), Pdifference = 0.322) ... Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone |
Nature Aging
2025 ✓ Peer-reviewed PMID 40155777 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The two-marker plasma model matched PET-based stages with a C index of 0.91 in both the derivation and validation cohorts, tracked clinical stage (C index 0.84-0.86) and aligned with autopsy ADNC (AUC 0.96), improving on %p-tau217 alone at the intermediate stage. |
Concordance of a plasma %p-tau217 plus eMTBR-tau243 staging model with amyloid/tau PET-based biological stages, clinical stage and autopsy-confirmed AD pathology | cohort study | 1,028 | A plasma-based model with %p-tau217 and eMTBR-tau243 was derived, which demonstrated high concordance with established PET-based stages (C index, 0.91; 95% CI, 0.90-0.92) and was associated with clinical stage within the AD continuum (C index, 0.84; 95% CI, 0.82-0.86). In the validation cohort, concordance with PET-based stages was high (C index, 0.91; 95% CI, 0.87-0.94), as was concordance with clinical stage (C index, 0.86; 95% CI, 0.82-0.89) ... In the neuropathology subsample, plasma staging was strongly aligned with autopsy-confirmed AD pathology using the Alzheimer Disease Neuropathologic Change scale (area under the curve, 0.96; 95% CI, 0.91-1.00) |
JAMA Neurology
2026 ✓ Peer-reviewed PMID 42189519 |
| Blood biomarkers (GFAP, NfL, p-tau217) for staging and prognosis Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Serum GFAP tracked post-mortem tau pathology independently of amyloid, correlated negatively with brain weight and cognition, correlated with astrocyte reactivity in tissue, and separated neuropathologically confirmed AD from non-AD dementias with AUC 0.91. |
Correlation of serum GFAP with post-mortem tau pathology, brain weight and astrocyte reactivity, and discrimination of autopsy-confirmed AD from non-AD dementia | cohort study | 139 | an association between serum GFAP level and post-mortem tau pathology (β = 12.85; P < 0.001) that was independent of amyloid deposits (β = 13.23; P = 0.02) ... a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = -0.35; P < 0.001) ... its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer's disease dementias from non-Alzheimer's disease dementias |
Brain
2024 ✓ Peer-reviewed PMID 38634687 |
| CSF alpha-synuclein seed amplification assay Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Smell testing followed by CSF seed amplification only in those with reduced smell predicted brain Lewy body pathology with 94% accuracy and cut CSF testing by 43%; in a living cohort it predicted CSF assay status with 79% accuracy. |
Accuracy for autopsy-confirmed Lewy body pathology and reduction in confirmatory CSF testing | cohort study | 1,567 | Among 358 autopsied participants, the two-step workflow predicted brain LBP with high accuracy overall (94%), and within clinical subgroups (clinical parkinsonism=95%; clinical Alzheimer's disease [AD]=94%; clinically unimpaired [CU]=93%). It reduced the need for confirmatory CSF testing by 43% overall (23% clinical parkinsonism; 35% clinical AD; 80% CU). In an independent in vivo cohort (N=1209), the workflow predicted CSF α-syn SAA status with 79% accuracy and reduced CSF testing by 26% |
Nature Communications
2025 ✓ Peer-reviewed PMID 40764485 |
| Dementia care management / navigation Care, carers and services | Treatment |
Benefit
whyDirection is for the Care Ecosystem programme: total cost of care was $475.80 per member per month lower than matched controls at 12 months, with fewer emergency, outpatient and professional visits. |
Total cost of care per member per month at 12 months versus propensity-matched controls | cohort study | 242 | Care Ecosystem participants had significantly lower total cost of care at 12 months, mean savings of $475.80 per member per month compared with controls |
American Journal of Managed Care
2024 ✓ Peer-reviewed PMID 39146484 |
| Naturalistic driving behaviour (digital marker of MCI) Care, carers and services | Treatment |
Benefit
whyDirection is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Driving features distinguished drivers with MCI from those with normal cognition (AUC 0.82), rising to 0.87 with demographics, APOE4 and cognition; drivers with MCI showed greater declines in trip frequency, night driving and route variety. |
Discrimination of MCI from normal cognition by daily driving features, and longitudinal change in driving | cohort study | 298 | Key features such as medium trip distance, speeding events, entropy, and maximum distance distinguished drivers with MCI from those with NC (area under the curve [AUC] 0.82, 95% CI 0.75-0.89). Adding demographics, APOE ε4, and cognitive composite improved AUC to 0.87 (95% CI 0.81-0.93) |
Neurology
2025 ✓ Peer-reviewed PMID 41296993 |
| Coffee, tea and flavonoid-rich foods Diet and supplements | Prevention |
Benefit
whyThe association was strongest at moderate intake rather than the highest. |
Incident dementia over a median 36.8 years | cohort study | 131,821 | HR 0.82 (95% CI 0.76-0.89) for highest vs lowest quartile of caffeinated coffee |
JAMA
2026 ✓ Peer-reviewed PMID 41661604 |
| Coffee, tea and flavonoid-rich foods Diet and supplements | Prevention |
Benefit
why882 cases across five quintiles and several interaction strata, so the subgroup estimates rest on small numbers. |
Incident dementia over a mean 9.2 years | cohort study | 121,986 | AHR 0.72 (95% CI 0.57-0.89) for highest vs lowest flavodiet quintile |
JAMA Network Open
2024 ✓ Peer-reviewed PMID 39292460 |
| Dietary pattern (general) Diet and supplements | Prevention |
Benefit
whyThe association is reported in people who already have elevated Alzheimer's blood markers, which is the point of the study. |
Incident dementia over a mean 8.4 years | cohort study | 1,865 | Dementia HR 0.71 (95% CI 0.58-0.88) per SD of anti-inflammatory diet adherence among participants with elevated p-tau217 |
JAMA Network Open
2026 ✓ Peer-reviewed PMID 42348207 |
| Dietary pattern (general) Diet and supplements | Prevention |
Benefit
whyIndependent of overall diet quality. Substituting olive oil for margarine or mayonnaise was also associated with lower risk; substituting for butter or other vegetable oils was not. |
Dementia-related death over 28 years | cohort study | 92,383 | HR 0.72 (95% CI 0.64-0.81) for dementia-related death with ≥7 g/day olive oil vs never/rarely |
JAMA Network Open
2024 ✓ Peer-reviewed PMID 38709531 |
| Dietary pattern (general) Diet and supplements | Prevention |
Benefit
whySignificant on one adherence score (MEDAS, HR 0.77) but not the other (PYRAMID, HR 0.86, 95% CI 0.73-1.02). |
Incident dementia over a mean 9.1 years | cohort study | 60,298 | HR 0.77 (95% CI 0.65-0.91) for highest vs lowest MEDAS tertile |
BMC Medicine
2023 ✓ Peer-reviewed PMID 36915130 |
| Mediterranean diet Diet and supplements | Prevention |
Benefit
whySignificant on one adherence score (MEDAS, HR 0.77) but not the other (PYRAMID, HR 0.86, 95% CI 0.73-1.02). |
Incident dementia over a mean 9.1 years | cohort study | 60,298 | HR 0.77 (95% CI 0.65-0.91) for highest vs lowest MEDAS tertile |
BMC Medicine
2023 ✓ Peer-reviewed PMID 36915130 |
| Physical activity (general / dose) Exercise and activity | Prevention |
Benefit
whyConcentrating activity into one or two days worked about as well as spreading it across the week. |
Incident dementia | cohort study | 91,512 | HR 0.73 (95% CI 0.60-0.89) for >300 min/week concentrated in 1-2 days vs <150 min/week |
Journal of Prevention of Alzheimer's Disease
2025 ✓ Peer-reviewed PMID 40514301 |
| Physical activity (general / dose) Exercise and activity | Prevention |
Benefit
whyDirection is for 12 weeks of cycle-ergometer exercise: putative glymphatic influx in the putamen and meningeal lymphatic vessel size and flow increased, and inflammation-related plasma proteins fell in step with the imaging changes. A mechanistic imaging result, not a cognitive outcome. |
MRI measures of glymphatic influx and meningeal lymphatic vessel size and flow, and plasma inflammatory proteins, after 12 weeks of cycling in healthy volunteers | cohort study | not stated | not established — pubmed abstract reports no numeric effect size. |
Nature Communications
2025 ✓ Peer-reviewed PMID 40204790 |
| Physical activity (general / dose) Exercise and activity | Prevention |
Benefit
why866 cases over a short follow-up for a disease with a long prodrome, so some of the association may be people already declining moving less. |
Incident all-cause dementia over a median 6.9 years | cohort study | 78,430 | HR 0.49 (95% CI 0.39-0.62) at 9,826 steps/day vs lowest activity |
JAMA Neurology
2022 ✓ Peer-reviewed PMID 36066874 |
| Physical activity (general / dose) Exercise and activity | Prevention |
Benefit
whyThe largest effect for physical activity anywhere in this table by a wide margin. On 678 cases over 6.3 years, in a disease with a long prodrome, reverse causation is the more likely explanation for an effect that size. |
Incident dementia over a median 6.3 years | cohort study | 84,854 | Trend across MVPA categories HR 0.66 (95% CI 0.62 to 0.70). "The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed < 300 MET/min/week." |
BMC Medicine
2021 ✓ Peer-reviewed PMID 34852818 |
| APOE genotype Genes (not modifiable) | Prevention |
Benefit
whyDirection is for carrying APOE2, which is associated with longer life irrespective of Alzheimer's status. The lifespan figures come from gene-targeted mice, not from the human cohort. |
Lifespan / survival | cohort study | 24,661 | Mice: "the median age at death was in the order of apoE2-TR (911 days) > apoE3 TR (825 days) > apoE4 TR (753 days) > Apoe KO (738 days)". In humans the abstract states only that "the association between APOE2 and longer lifespan persisted irrespective of AD status", without a numeric estimate. |
eLife
2020 ✓ Peer-reviewed PMID 33074098 |
| Rare protective or risk variant (APOE3 Christchurch, APOE R145C, RELN, FN1) Genes (not modifiable) | Prevention |
Benefit
whyDirection is for one copy of the APOE3 Christchurch variant: median onset of cognitive impairment at 52 versus 47 years in matched PSEN1 E280A carriers without it, with preserved brain metabolism and fewer vascular amyloid features in the few imaged or autopsied. Not modifiable. |
Age at onset of cognitive impairment in PSEN1 E280A carriers | cohort study | 1,077 | the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49) |
New England Journal of Medicine
2024 ✓ Peer-reviewed PMID 38899694 |
| Hearing loss / hearing aids Hearing and vision | Prevention |
Benefit
whyConfined to people who said the aid actually improved their hearing (HR 0.86); those reporting poor improvement showed nothing (HR 0.98). |
Probable dementia over a mean 6.5 years | cohort study | 61,089 | HR 0.91 (95% CI 0.88-0.94) for hearing aid use; HR 0.86 (0.80-0.93) with effective use |
Cell Reports Medicine
2026 ✓ Peer-reviewed PMID 42127901 |
| Herpes zoster / shingles vaccination Infection and vaccination | Prevention | Benefit | New dementia diagnoses over 5.5 years | cohort study | 232,124 | -2.0 percentage points (95% CI -3.5 to -0.4) absolute reduction in new dementia diagnoses over 5.5 years |
The Lancet Neurology
2026 ✓ Peer-reviewed PMID 41579903 |
| Herpes zoster / shingles vaccination Infection and vaccination | Prevention |
Benefit
whyRegression discontinuity across a birth-date eligibility threshold, which makes confounding by health-seeking behaviour less likely than in a plain cohort comparison. Eligibility did not change uptake of other preventive services or other chronic-disease diagnoses, which is the check that makes the design convincing. |
New dementia diagnoses over 7.4 years | cohort study | 101,219 | "eligibility for HZ vaccination (ie, being born shortly after vs shortly before November 2, 1936) decreased the probability of receiving a new dementia diagnosis during 7.4 years by 1.8 percentage points (95% CI, 0.4-3.3 percentage points; P = .01)"; vaccination uptake rose 16.4 percentage points (95% CI 13.2-19.5) across the threshold |
JAMA
2025 ✓ Peer-reviewed PMID 40267506 |
| Herpes zoster / shingles vaccination Infection and vaccination | Prevention |
Benefit
whyRegression discontinuity across the 2 September 1933 eligibility threshold; stronger in women than men. |
Probability of a new dementia diagnosis over 7 years | cohort study | not stated | -3.5 percentage points (95% CI 0.6 to 7.1, P = 0.019) in 7-year dementia diagnosis probability; 20.0% relative reduction (95% CI 6.5-33.4) |
Nature
2025 ✓ Peer-reviewed PMID 40175543 |
| Antipsychotics (harms / discontinuation) Medicines | Treatment |
Benefit
whyDirection is for STOPPING the antipsychotic: discontinuers were hospitalised less than matched continuers. |
Hospitalisation, pneumonia and urinary tract infection | cohort study | 4,222 | All-cause hospitalisation HR 0.83 (95% CI 0.72-0.96); pneumonia hospitalisation HR 0.51 (0.29-0.90) |
Alzheimer's Research & Therapy
2026 ✓ Peer-reviewed PMID 42410659 |
| Antipsychotics (harms / discontinuation) Medicines | Treatment |
Benefit
whyDirection is for discontinuation: tapering after 12 weeks lowered the 24-month absolute risk of delirium and fracture versus continuing, with no difference in stroke, pneumonia or death. Results were similar for abrupt discontinuation and after 24 weeks. |
24-month risk of delirium, fracture, stroke, pneumonia and death after tapering or stopping antipsychotics versus continuing | cohort study | 24,822 | Compared with continuation after 12 weeks of treatment, estimated risks of delirium and fracture under the tapering strategy corresponded to 24-month ARDs of -2·46% (95% CI -4·10 to -1·27) and -2·80% (-4·14 to -1·29), respectively. Estimated risks for stroke, pneumonia, and all-cause mortality were similar between strategies |
The lancet. Healthy longevity
2026 ✓ Peer-reviewed PMID 42302797 |
| Cholinesterase inhibitor / memantine Medicines | Treatment |
Benefit
whyObservational: 80% of residents were on no anti-dementia drug, so who gets prescribed and who does not may itself track prognosis. |
All-cause mortality | cohort study | 25,358 | Adjusted hazard ratios for mortality vs no anti-dementia drug: "HR: 0.826, 95%CI 0.769 to 0.888 for AChEI; 0.857, 95%CI 0.795 to 0.923 for memantine; 0.742, 95%CI 0.640 to 0.861 for AChEI plus memantine" |
Alzheimer's Research & Therapy
2024 ✓ Peer-reviewed PMID 38812028 |
| Cholinesterase inhibitor / memantine Medicines | Treatment |
Benefit
whyCholinesterase inhibitors, not memantine: -0.39 MMSE points a year against -2.50 with no treatment. The mortality benefit held only in the first year. Registry data with weighting, not a trial. |
MMSE decline per year; mortality | cohort study | 1,095 | MMSE change: -0.39 points/year (95% CI -0.96 to 0.18) with cholinesterase inhibitors vs -2.49 (-4.02 to -0.97) with memantine and -2.50 (-4.28 to -0.73) with non-use. Mortality in the first year after diagnosis: adjusted HR 0.66 (95% CI 0.46 to 0.94) |
Alzheimer's & Dementia
2024 ✓ Peer-reviewed PMID 39177108 |
| GLP-1 receptor agonist Medicines | Prevention |
Benefit
whySeven separate comparisons against seven other antidiabetic drugs, so the comparator is always another drug rather than no treatment. |
First-time Alzheimer's diagnosis over 3 years | cohort study | 1,094,761 | HR 0.33 (95% CI 0.21-0.51) vs. insulin; HR 0.59 (95% CI 0.37-0.95) vs. other GLP-1 agonists |
Alzheimer's & Dementia
2024 ✓ Peer-reviewed PMID 39445596 |
| Metformin / antidiabetic Medicines | Prevention |
Benefit
whyComparator is other oral antidiabetic drugs, not no treatment. |
All-cause dementia and Parkinson's disease | cohort study | 358,862 | All-cause dementia aHR 0.79 (95% CI 0.69-0.90) for SGLT2 inhibitor vs other oral antidiabetic drugs |
Neurology
2024 ✓ Peer-reviewed PMID 39292986 |
| Metformin / antidiabetic Medicines | Prevention |
Benefit
whyThe exposure actually studied is STOPPING metformin early, which carried 21% higher dementia incidence than staying on it. Read as indirect support for metformin, not as a trial of it. |
Incident dementia | cohort study | 41,346 | HR 1.21 (95% CI 1.12-1.30) for dementia after early metformin termination |
JAMA Network Open
2023 ✓ Peer-reviewed PMID 37878309 |
| SGLT2 inhibitor Medicines | Prevention |
Benefit
whyFor SGLT2 inhibitors specifically: HR 0.86 (95% CI 0.79-0.94) against DPP4 inhibitors, and HR 0.70 in the as-treated analysis. |
Incident dementia | cohort study | not stated | SGLT2i vs DPP4i HR 0.86 (95% CI 0.79-0.94); GLP1-RA vs DPP4i HR 0.95 (0.87-1.04) |
Alzheimer's Research & Therapy
2025 ✓ Peer-reviewed PMID 41420258 |
| Statins / lipid-lowering Medicines | Prevention |
Benefit
whyBenefit was confined to APOE4 carriers (HR 0.60) and absent in non-carriers (HR 0.96). Observational, and it disagrees with the larger target-trial emulation that found nothing. |
Incident clinical Alzheimer's disease and cognitive decline | cohort study | 4,807 | Alzheimer's HR 0.81 (95% CI 0.70-0.94) overall; 0.60 (0.49-0.74) in APOE ε4 carriers; 0.96 (0.82-1.12) in non-carriers |
Neurology
2024 ✓ Peer-reviewed PMID 38447103 |
| Education / cognitive reserve Sleep, mood and social life | Prevention |
Benefit
whyDirection is for MORE education. Up to a quarter of the effect ran through midlife vascular risk factors, and the authors say treating those factors would not close the educational gap. |
Incident dementia | cohort study | 13,368 | 8-44% lower dementia risk with higher education vs grade school; up to 25% mediated by midlife vascular risk factors |
Annals of Neurology
2023 ✓ Peer-reviewed PMID 36966451 |
| Social isolation / loneliness Sleep, mood and social life | Prevention |
Benefit
whySignificant only for contact measured at age 60, not at 50 or 70. The authors note that keeping up contact may itself be a marker of cognitive reserve rather than a cause of it. |
Incident dementia over 28 years | cohort study | 10,228 | HR 0.88 per SD higher social contact frequency at age 60 (95% CI 0.79-0.98) |
PLoS Medicine
2019 ✓ Peer-reviewed PMID 31374073 |