Every row of the evidence table

The key point: the observational analysis showed light drinking looking protective, but the genetic (Mendelian randomisation) analysis did not, which the authors read as the protective appearance coming from people cutting down in early dementia.

This 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.

Sustained mild and moderate drinking carried lower risk than not drinking, sustained heavy drinking higher risk, and cutting down from heavy to moderate lower risk. Observational, with the same abstainer problem.

U-shaped: long-term abstainers had 47% higher risk than moderate drinkers, and above 14 units a week each extra 7 units raised risk by 17%. Neither end of the range looks like a benefit of drinking.

The exposure is cannabis use severe enough to need hospital care, not cannabis use in general, and the comparison is against other acute-care patients as well as the general population.

Direction 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.

The two measures moved in opposite directions over 2015-2021: standardised incidence fell from 3.5% to 2.8% per year while prevalence rose from 10.5% to 11.8%; gaps between Black or Hispanic and White beneficiaries narrowed.

Direction is for more recent birth cohort: after controlling for age and period, later-born cohorts were less likely to have dementia in all three regions, more so among women; the point estimates for men in England were not significant.

Direction is for later birth cohort: each successive cohort had a significantly lower incident dementia rate, independent of sex, education and age.

Direction is for the later survey year: prevalence fell from 11.6% to 8.8%, with rising education associated with some of the decline despite a worse cardiovascular risk profile.

Direction 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.

Direction is for the later-born population: prevalence was 6.5% against the 8.3% expected from the earlier study (odds ratio 0.7), which the authors read as a cohort effect.

Incidence was consistently but non-significantly lower in the 2000 subcohort (rate ratio 0.75, 95% CI 0.56-1.02, borderline). The authors read the pattern, together with lower mortality and larger brain volumes, as suggesting a decline, but the primary comparison did not reach significance.

Direction is for degenerative pathology profiles: more than 80% had mixed pathologies, and of five clustered profiles the LATE-NC/hippocampal sclerosis and the ADNC/amyloid angiopathy profiles showed the fastest cognitive decline.

Direction is for LATE-NC: found in 64% of brains, stages 1a, 2 and 3 were associated with dementia and lower MMSE, it was among the strongest independent predictors of dementia, and its attributable risk (24.2%) exceeded that of Alzheimer's neuropathologic change (18.6%); it usually occurred alongside other pathologies.

Direction is for carrying the risk factors. The Danish estimate (37.8% across 16 factors) is lower than the Lancet Commission's global 45%.

Direction is for carrying the risk factors: depression, diabetes, low education, smoking, obesity, physical inactivity and alcohol overconsumption each independently raised the hazard of early-onset dementia, and most associations were stronger for early-onset than late-onset dementia.

Direction is for carrying the risk factors. Which factor mattered most differed by APOE risk group, on 2,065 cases split across 11 factors and three genetic strata, so the subgroup estimates are imprecise.

Direction is for carrying hypertension, diabetes or smoking. The attributable share rose with the age at which the factors were measured (22% at 45-54, 44% at 65-74), which is what you would expect if some of it is reverse causation rather than cause.

Direction is for carrying the risk factors: the Commission attributes 45% of cases to 14 modifiable factors, which is the same number read the other way as prevention potential. The Commission's own caveat is that "some associations might be only partly causal".

Direction is for carrying the risk factors. 39 candidate factors were screened against 485 cases, so individual estimates are imprecise.

Direction is for carrying the risk factors. The weighted combined estimate (32.0% for seven factors) is lower than the Lancet Commission's 45% for 14.

For the vascular risk factors: up to a quarter of the education-dementia association ran through hypertension, diabetes and related midlife factors, so carrying them accounted for part of the excess risk.

Direction is for carrying the peripheral diseases: together they were related to about one-third of global dementia burden, led by periodontal disease, chronic liver disease, hearing loss, vision loss and type 2 diabetes. Attributable fractions assume the pooled associations are causal.

A burden-of-disease decomposition: age-standardised rates rose slightly and population growth was the largest driver of the rise in cases. It compares no exposure, so no direction is recorded.

A lifetime-risk estimate (42% after age 55, higher in women, Black adults and APOE4 carriers) and a projection of new cases. It compares no exposure, so no direction is recorded.

A pooled incidence and prevalence estimate with no exposure compared, so no direction is recorded.

A prevalence estimate and forecast: cases are projected to rise from 57.4 million to 152.8 million while age-standardised prevalence stays flat, with the rise attributed to population growth and ageing. It compares no exposure, so there is no direction to record.

A pooled prevalence estimate with no exposure compared, so there is no direction to record.

Direction is for being African-American or American Indian/Alaska Native relative to Asian-American members: incidence was highest in those groups (26.6 and 22.2 per 1000 person-years) and lowest in Asian-Americans (15.2). The authors present this as a benchmark for reducing disparities, not as a biological effect of race.

A position paper from an expert network. It sets out 12 priority research areas on sex and gender in Alzheimer's disease and reports no effect estimate.

Direction is for female sex: at higher amyloid levels women had higher plasma p-tau217 than men, greater tau deposition and accumulation at a given p-tau217 level, and faster cognitive decline in two of the cohorts.

Direction is for female sex: women had higher odds of a high neuritic plaque burden than men after adjustment, and were more likely to reach Braak stage V-VI. Black non-carriers and non-carriers of African ancestry were least likely to have high plaque burden, a protection weakened in ε4 carriers.

A threshold-derivation meta-analysis: it converges on 18 Centiloids (data-driven) and 27 Centiloids (visual reads) and flags 11-26 as a range to read with caution. It compares no exposure, so no direction exists to record.

Appropriate use criteria rated by consensus: for amyloid PET seven of 17 scenarios were rated appropriate, two uncertain and eight rarely appropriate; for tau PET five, six and six. No effect estimate is reported.

Direction is for higher baseline plasma p-tau217 in cognitively unimpaired women: each SD increase more than doubled the hazard of MCI or dementia. Associations were larger in women over 70, APOE4 carriers and White women, and p-tau217 was not associated with incident MCI in Black women.

Direction 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.

Direction is for higher baseline plasma p-tau217 in cognitively unimpaired adults: each SD raised the hazard of progression by 38%, and the very-high group had a 38% absolute 5-year risk of progression.

Direction is for higher plasma p-tau217: each SD raised the hazard of incident cognitive impairment by 41%, more steeply in APOE-ε4 carriers (76%) than non-carriers (26%), with survival curves separating 3-4 years after the blood test.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Stand-alone plasma p-tau217 gave 81% accuracy and 79% PPV; confirming positives with PET or CSF raised both to 91% while cutting PET scans needed to find 100 amyloid-positive people from 536 to 124. Immunoassays matched mass spectrometry on PPV but had lower accuracy.

Direction 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.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. All four assays (Lumipulse, Johnson & Johnson, ALZpath, NULISA) gave statistically equivalent AUCs of 0.84-0.90 for amyloid positivity, with cross-platform correlations of 0.40-0.86.

An editorial reviewing the FDA clearance of the Lumipulse plasma ratio test. It relays performance figures from the FDA summary and other studies and reports no data of its own.

Direction is for the blood test's ability to detect treatment-related amyloid clearance on PET: AUC 0.61, which the authors call suboptimal and not currently usable for that purpose. It says nothing about the drug's effect.

Direction 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.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Subgroup-specific optimal cutoffs and a double-cutoff strategy both improved accuracy over the standard single cutoff, most markedly in chronic kidney disease (0.65 to 0.83) and anaemia.

The review's own summary points two ways: CSF biomarker tests were mostly cost-effective against cognitive assessment or imaging, while blood biomarker tests showed mixed results; every included study was model-based.

The findings point two ways: the p-tau217/Aβ42 ratio tracked AD-related factors (MCI, AD dementia, future progression, age, APOE ε4) more closely than either marker alone and had few intermediate results, but it was also related to kidney function, diabetes and hearing loss, and medical morbidities were most frequent among intermediate classifications.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The prespecified APS2 cut point gave 91% accuracy, 90% sensitivity and 92% specificity against amyloid PET.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 detected amyloid PET positivity with 82% sensitivity and 86% specificity, comparable to CSF p-tau217; less sensitive for tau PET.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. AUC 0.93-0.96; accuracy 89-91% in secondary care and 85% in primary care, lower (83%) at age 80 or older; a two-cutoff approach raised accuracy to 92-94% at the cost of 12-17% intermediate results.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 was the best-performing marker (88.1% sensitivity, 88.7% specificity, AUROC 91.1%, moderate certainty), ahead of p-tau181 and p-tau231; about 90% of studies were at high risk of bias.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The Pitt-p-tau217 assay separated PSEN1 carriers from controls (AUC 0.94) and amyloid PET-positive from -negative cognitively normal adults (AUC up to 0.84), equivalent to the ALZpath assay.

A clinical practice guideline. It sets performance thresholds for blood tests (at least 90% sensitivity and 75% specificity for triage; at least 90% for both to substitute for amyloid PET or CSF) and reports no effect estimate of its own.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Performance varied widely across tests, from 49.3% to 91.4% pooled sensitivity and 61.5% to 96.7% pooled specificity at a single cut-point, with most studies at high risk of bias.

Direction 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.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The Lumipulse plasma p-tau217/Aβ42 ratio reached AUC 0.963-0.966 for amyloid PET and 0.947-0.974 for tau PET, equivalent to CSF tests and better than plasma p-tau217 alone, with fewer intermediate results.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217/Aβ42 had the highest accuracy (0.88 in Black and 0.91 in White participants) and fewest intermediate results, with no difference in classification by race.

Direction is for chronic kidney disease as a source of false signal: at eGFR 45 versus 60, p-tau217 was 31-55% higher in amyloid-negative people on two immunoassays, a rise largely removed by using the %p-tau217 ratio. A test-validity result, not a health outcome.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma p-tau217 identified symptomatic AD with 95% sensitivity and 82% specificity (86% with the Aβ42 ratio) and tracked CSF biomarkers closely (AUC 0.94-0.96); reduced kidney function raised levels in patients without AD.

A price-threshold model: it estimates the test price at which diagnostic cost per true-positive case equals standard care ($290-$1,950 depending on use), and compares no actual price against it, so there is no direction to record.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The APS2 blood test reached AUC 0.96-0.97 and 88-92% accuracy, and its 91% accuracy for clinical AD beat primary care physicians (61%) and dementia specialists (73%).

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. APS2 gave AUC 0.94 and 88% agreement with amyloid PET, with similar performance by ethnicity, sex, age and APOE4 status.

Direction 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%.

Direction 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.

A workgroup recommendations document. It sets target sensitivity and specificity for blood biomarker tests (≥90% / ≥85% for triage in primary care; ~90% / ~90% as a confirmatory test) and reports no data of its own.

Direction 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%.

Direction 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.

The results point different ways: diagnostic confidence rose 1.43 points, but diagnosis changed in only 17.2% and management in 27.7%, below the 30% threshold the investigators set as clinically significant; a non-elevated result reduced amyloid PET use, and patients with elevated results had higher anxiety at 2-3 months.

The findings point different ways: lower eGFR raised every blood biomarker except Aβ42/40 (a test-interpretation caveat), yet impaired kidney function did not itself raise dementia risk (HR 0.93), while the association between high NfL and dementia was about twice as strong in people with impaired kidneys.

Direction 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.

Direction is for abnormal baseline plasma p-tau217: people positive for both plasma amyloid and tau progressed to MCI at 7.8 times the rate of those negative for both, and tau-positive/amyloid-negative people at 4.3 times. CSF and PET gave similar results; adding plasma Aβ42/40 did not improve prediction.

The two measures behaved differently: baseline plasma p-tau217 predicted later cognitive decline about as well as entorhinal tau PET (ρ -0.47 vs -0.55), but over time p-tau217 rose then decelerated and tracked concurrent cognitive change only weakly (ρ -0.24) or not at all in the PET substudy, whereas regional tau PET change correlated strongly with concurrent decline.

Direction is for higher baseline plasma GFAP in cognitively unimpaired adults: it predicted faster cognitive decline, CDR progression, cortical atrophy and conversion to amyloid positivity, with stronger effects in females.

Direction is for higher plasma pTau217: it was associated with global and domain-specific cognitive decline within both racial groups and discriminated 3-year dementia well (AUC 0.81 in Black and 0.77 in White adults); biomarker levels were similar across races and the association with decline was similar, though pTau217 tracked faster global and semantic memory decline in Black adults.

Direction is for adverse biomarker levels: only the Alzheimer-specific markers measured in midlife (lower Aβ42:Aβ40, higher p-tau181) predicted dementia two decades later, while every marker measured in late life did, NfL most strongly (HR 1.92 per SD). Biomarkers changed faster in APOE ε4 carriers and with midlife hypertension or diabetes.

Direction is for high serum NfL or GFAP: the top tertile of either raised incident dementia risk by 38-49% and roughly tripled dementia-specific mortality; being in the top tertile of both doubled dementia risk and raised dementia mortality nine-fold. NfL was independently associated with faster cognitive decline.

Direction is for astrocyte reactivity: amyloid was associated with higher plasma p-tau only in people positive for astrocyte reactivity, and an AD-like pattern of tau-PET accumulation as a function of amyloid appeared only in those individuals, cross-sectionally and longitudinally.

Direction is for a rising serum NfL: its rate of change separated mutation carriers from non-carriers 16.2 years before expected symptom onset (versus 6.8 years for a single level), peaked around symptom conversion, and predicted cortical thinning and cognitive decline.

Direction is for microglial activation: amyloid was associated with astrocyte reactivity across cortical regions only when microglia were activated, and that microglia-dependent reactivity related to cognitive impairment through tau phosphorylation and aggregation.

Direction 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.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Plasma Aβ42/40, p-tau217, p-tau181 and NfL classified AD with AUC 83% and FTLD with 88%, consistent across countries, rising to 89% and 95% when combined with neuroimaging patterns and cognitive measures.

The three markers pointed different ways: plasma p-tau217 distinguished amyloid/tau stages, GFAP tracked amyloid-driven tau progression, and NfL was only weakly linked to Alzheimer pathology and, in the authors' words, inadequate as a neuronal injury biomarker for AD.

The result points two ways: p-tau181 gave the best AUC for separating AD from controls, frontotemporal dementia and amyloid-negative Lewy body dementia, but that discrimination could not be reproduced when pre-defined cut-offs were applied, so cohort-specific cut-offs were needed.

Direction 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.

Direction is for higher baseline plasma GFAP: it detected abnormal CSF amyloid (AUC 0.79, 0.86 with APOE4) and predicted later conversion to Alzheimer's dementia (AUC 0.84); GFAP slopes were steeper in those who progressed.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Results ranged from 55% to 100% sensitivity and 60% to 100% specificity across four laboratories using different protocols, with only fair agreement between them (kappa 0.246).

Direction 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.

A pooled prevalence among carers (50.8% lonely, 37.1% socially isolated) with no non-carer comparison, so no direction for the effect of caregiving can be recorded.

No significant difference in 5-year cumulative spending between spouses of people with and without dementia ($3,974, 95% CI -$3,199 to $11,477); year-5 spending was higher (+$2,748), driven by inpatient costs.

Direction is for BEING a carer: carers were worse off than non-carers on every domain, with the largest gaps in depression and stress.

Only STRAINED carers were at higher risk (RR 1.63, 95% CI 1.00-2.65, with the interval touching 1). Carers who reported no strain showed nothing (RR 1.08), so it is the strain rather than the caregiving that carries the signal.

Benefit was larger for younger, male and non-spousal carers. The largest single effect (training the person with dementia) rests on 10 observations and the authors call it promising rather than definitive.

A pilot designed to test feasibility; 68 carers and a 2-week outcome.

Digital psychological interventions reduced caregiver burden and improved self-efficacy and quality of life; the effect on depressive symptoms was not statistically significant (P = .06).

No difference from waitlist control on the primary burden outcome or on mood, WHOQOL-Bref or productivity; only the CarerQoL-VAS quality-of-life score was higher in the intervention group. The trial recruited 93 of a 194 target.

At the 1-month comparison the automated self-guided programme reduced depression and burden and increased positive gains versus waitlist; anxiety did not differ. Group differences mostly disappeared once controls received the programme.

Peer support reduced distress to behavioural symptoms and increased social support and quality of life immediately after the intervention, but had no effect on depression/anxiety, loneliness, burden or competence, and no outcome was sustained at follow-up.

A factorial trial of components: the mindfulness component carried the benefit and amplified the others.

Burden fell in both arms with no significant difference between the two platforms. There was no untreated control, so the within-arm improvement cannot be separated from time or attention.

Direction is for NIDUS-Family: an 89% probability of cost-effectiveness from a health and social care perspective (87% societal) and £8,934 (37%) lower average costs, though the cost difference's confidence interval includes zero.

The outcome is how prepared carers felt to decide about firearm access, not whether any injury was avoided.

Direction is for psychosocial and pharmacological interventions, which the review reports as showing mild to modest efficacy in high-quality meta-analyses. A narrative clinical review summarising other meta-analyses, not a new pooled estimate.

Benefit in Hispanic and White caregivers and in Black spousal caregivers; not in Black non-spousal caregivers.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Tablet tests correlated strongly with MMSE, MoCA and Trails A (r > 0.7) and the Match test separated amyloid-positive from -negative patients (AUC 0.82) better than MMSE or MoCA (0.75).

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Pooled sensitivity 76% and specificity 83% for dementia, with 73% / 84% in primary care; the authors call it a practical screening tool while noting high or unclear risk of bias in patient selection and timing.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. The two-stage GPCOG had sensitivity 0.85 and specificity 0.86 against DSM-IV dementia, and was superior to the Abbreviated Mental Test.

The two comparisons point different ways: overall utilization and payments were similar between amyloid-positive (A4) and amyloid-negative (LEARN) participants, but among A4 participants claims indicators of progression carried 45-103% higher payments.

A cost estimate ($818 billion, 80% of it borne by families through unpaid care, earnings losses, out-of-pocket costs and quality-of-life losses) with no exposure compared, so no direction is recorded.

A descriptive spending analysis with no exposure compared, so there is no direction to record: Part D spending rose with dual-eligibility duration, Part B drug spending varied widely by state, and ACO enrollment made only a modest difference.

Direction is for having AD dementia: lifetime formal-care costs of 2,440,000 SEK against 510,000 SEK for matched controls, with prescriptions and social care rising and specialist outpatient visits falling as the disease advanced. A cost result, not a health outcome.

A cost projection: total burden is estimated at $344 billion in 2020 rising to over $3 trillion in 2060, with African American and Latino families projected to bear a disproportionate share. It compares spending shares between groups but tests no exposure, so no direction is recorded.

A cost estimate with no exposure compared, so there is no direction to record. Higher unpaid-care costs went with lower medical spending on nursing facility care.

A cost projection with no exposure compared, so there is no direction to record. Dementia's share of replacement cost is projected to rise from 44% to 53%.

A cost estimate with no exposure compared, so there is no direction to record.

Direction is for greater disease severity: mean annual costs rose from SEK 99,906 in MCI to SEK 795,617 in severe AD (SEK 57,625 to 668,073 in the amyloid-confirmed subset), driven by institutionalisation, home care and daytime support while outpatient costs fell. A cost result, not a health outcome.

Direction is for being on the Alzheimer's continuum: societal costs were 52% higher in subjective cognitive decline, 170% in MCI and 307% in AD dementia than in controls, and payer costs 26%, 85% and 36% higher. A cost result, not a health outcome.

A cost estimate and projection with no exposure compared, so there is no direction to record.

A cost estimation across 204 countries with no exposure compared, so there is no direction to record.

Direction is for being non-Hispanic Black or Hispanic rather than non-Hispanic White: disease-course Medicare spending was higher ($165,730 and $160,442 versus $136,326), highest for Black beneficiaries in every phase and driven by high-cost services in the last year of life. A disparities result, not a biological effect of race.

Direction is for dying with dementia rather than heart disease, cancer or other causes: total cost was higher ($287,038) and out-of-pocket spending 81% higher, consuming 32% of household wealth versus 11%.

Direction is for living in the community rather than a nursing home: unadjusted costs were lower in the community, but after adjusting for functional impairment and comorbidity community care cost €11,344 more per year, mainly through informal care. A cost result, not a health outcome.

Direction is for having dementia: the attributable yearly cost per person was $41,689-$56,290 depending on how informal care is valued, a burden the authors call similar to heart disease and cancer.

Direction is for value for money at current Australian prices: donanemab improved modelled QALYs (4.38 vs 4.01) but the ICER of $342,424 per QALY exceeded commonly cited willingness-to-pay thresholds. An unfavourable value result, not a clinical harm.

A threshold analysis estimating what each country should be willing to pay (from $4-$18 a year in low-income countries to $254-$9,434 for lecanemab and $387-$13,964 for donanemab in high-income countries). It sets no price against an actual list price, so there is no direction to record.

The review splits by drug class: at $100,000 per QALY every study found memantine cost-effective and more than half found the cholinesterase inhibitors so, whereas aducanumab, lecanemab and donanemab were not cost-effective in any study. A value result, not a clinical harm.

A cost-effectiveness model reporting ICERs of JPY 8.5 million and 7.9 million per QALY without stating a threshold or a verdict; the authors argue that narrow value assessments understate social value. No direction is recorded.

Direction is for value for money: three years of lecanemab gained 0.17 QALYs and the cost-effective price at 1 million SEK per QALY was 33,886 SEK a year, which the authors say makes it unlikely to be cost effective in Sweden at current US list prices. An unfavourable value result, not a clinical harm.

Direction is for value for money at the current price: no lecanemab strategy was cost-effective against standard care alone, whichever diagnostic test was used; CSF-guided targeted treatment would become cost-effective below $5,100 per year. An unfavourable value result, not a clinical harm.

Direction is for chronic bi-weekly intravenous infusion relative to oral treatment: administration and monitoring cost $45,208 plus $6,095 caregiver burden, eroding 44% of treatment value, against 2% for an oral drug. A cost result for a hypothetical treatment, not a clinical harm.

Direction is for value for money at the list price: the benchmark price ($8,900-$21,500 per year) sits below the $26,500 list price, the committee voted 15-0 that the drug represents low long-term value at that price and 12-3 that the evidence did not adequately demonstrate a net health benefit. An unfavourable value assessment, not a clinical harm.

Direction is for value for money at the assumed $28,000 annual price: ICERs of $981,000/QALY (aducanumab) and $193,000/QALY (donanemab) exceed the $150,000/QALY threshold, so neither was cost-effective. An unfavourable value result, not a clinical harm.

Direction is for value for money: APPLE-Tree had a 96% probability of being cost-effective per cognition point at a £30 000 threshold but only 12% on QALYs, which were slightly lower in the intervention arm. Post hoc subgroups suggested better value in non-White and socioeconomically disadvantaged participants.

Direction is for value for money: the intervention was modelled as dominant, saving JPY 452,826 per person and adding 0.08 QALYs over 35 years, with sensitivity analyses described as confirming robustness. A model extrapolating an 18-month trial.

The community health worker programme achieved verified linkage to medical care in 16.7% of dyads versus none in the control arm. Caregiver outcomes were largely unchanged, with self-efficacy favouring control.

No difference between health-system care, community-based care or usual care on either primary outcome. Caregiver self-efficacy did improve in both active arms.

Direction is for the extended nursing role intervention: 74% fewer unmet needs and higher quality of life at six months, with a small QALY gain at about 1,425 EUR added cost; no effect on caregiver burden.

The two perspectives disagree: the digitally supported care management system dominated usual care for the public payer (lower costs, marginally more QALYs, 72-79% probability of cost-effectiveness) but cost €331,000 per QALY from a societal perspective (33-35% probability).

Direction 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.

Direction is for collaborative dementia care management: fewer neuropsychiatric symptoms, lower caregiver burden, better mental health and 0.137 QALYs gained at no significant added cost (3186€ per QALY) over 36 months; no difference in antidementia drug use, overall quality of life or inappropriate medication.

No benefit and no harm: screening did not change family-member quality of life, preparedness or self-efficacy, and did not raise depression or anxiety. Only 5.1% screened positive.

The outcome is how many diagnoses were made, not whether anyone was better off. The passive digital marker alone did not raise detection (AOR 0.84, 95% CI 0.63-1.11).

MCI was diagnosed sooner (HR 1.21) but dementia diagnosis barely moved (HR 1.04, 95% CI 1.02-1.06). The outcome is detection, not health.

A criteria document. It defines Alzheimer's disease biologically and sets out staging, and reports no effect estimate.

An editorial. It argues that biomarker positivity alone should not define Alzheimer's disease in people without symptoms, and reports no data of its own.

A research framework defining Alzheimer's disease by biomarkers (the AT(N) system) for research use. It states its own intended limits and reports no effect estimate.

Consensus guidance for primary care on disclosing and communicating a dementia diagnosis, developed with patients, care partners and clinicians. It reports no effect estimate.

A clinical practice guideline. It sets out a structured, patient-centred process for evaluating, diagnosing and disclosing suspected Alzheimer's disease or related dementias in any practice setting, and reports no effect estimate.

Direction is for a lower (worse) glymphatic index: it was lowest in AD dementia and predicted faster amyloid accumulation, amyloid-positive transition, atrophy, clinical progression and cognitive decline, with the cognitive effect fully mediated by amyloid PET and atrophy.

Difference-in-differences around ACO entry found no change in end-of-life care processes, outcomes or spending.

A single-programme implementation report with no comparison group. It counts enrolment and service use and estimates no effect.

Implementation guidance drawn from six earlier comprehensive dementia care programmes. It reports no effect estimate of its own.

Direction is for the benefit redesign: projected out-of-pocket drug spending fell 55% ($56 to $25) for low-income-subsidy beneficiaries and 25% ($772 to $576) for others, with larger reductions for people with 6-8 comorbidities.

Admission showed no evidence of an effect on 30-day mortality or subsequent inpatient days, but raised 30-day health care spending by $2547. An instrumental-variable estimate for marginal admissions.

Direction is for co-existing Lewy body pathology in people with Alzheimer pathology: worse baseline cognition, faster global cognitive decline and more posterior hypometabolism than Alzheimer pathology alone. The seed amplification assay itself agreed closely with autopsy (96.3% sensitivity, 96.4% specificity in 61 cases).

A classification-validation study without a neuropathological reference standard, so accuracy cannot be judged. The groups behaved as expected: patients labelled LATE had mild amnestic impairment, limbic atrophy and stable MMSE over 30 months, while AD and AD/LATE groups declined.

Direction 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.

Advance care planning strongly increased DNR documentation (OR 14.12) but did not change whether residents died in the nursing home (OR 1.62, 95% CI 0.72-3.66). Evidence on other end-of-life outcomes was limited and inconsistent, and no study came from a non-Western setting.

The primary outcome did not improve. Emergency department visits and hospitalisations were lower (RR 0.45, 95% CI 0.31-0.65), which is a secondary outcome.

A Delphi consensus among 60 international expert panellists, reaching agreement on 15 major and 42 minor referral criteria. No patient outcome is measured and no effect is estimated.

Direction is for the AD-associated complement pattern: age-related falls in C4, C4b, Factor I and Properdin and rises in Factor D were more pronounced in people who later developed AD, detectable in the preclinical phase, and the same profile was specific to AD among dementia subtypes.

Direction is for the test's accuracy against the reference standard; an accuracy result, not a health outcome. Cross-validated balanced accuracy of 70-95% and AUC above 78% across the six conditions; the model is a development-stage tool with one external memory-clinic validation sample.

A prognosis meta-analysis: it pools time to death and to nursing home admission and compares no exposure. Women's shorter survival was attributable to later age at diagnosis.

Three trials comparing respite with no respite found no significant benefit on any carer outcome; the four included trials were too different to pool.

The outcome is how prepared carers felt to decide about firearm access, not whether any injury was avoided.

Direction is for an older-than-chronological sleep EEG brain age: each 10-year increase in the index was associated with a 39% higher risk of incident dementia, consistent across sex and age groups.

Direction is for DREAMS START against treatment as usual: a 78% probability of being cost-effective at £20,000 per QALY, with cost and QALY differences individually non-significant. The clinical sleep result is in the table under its own row.

Direction is for amyloid: it induced hyperconnectivity from tau epicentres to posterior tau-vulnerable regions, present already in preclinical AD, and this hyperconnectivity mediated amyloid's effect on faster tau accumulation.

Direction is for greater spatial extent of tau: it tracked memory in unimpaired people and executive function in MCI and dementia better than a temporal meta-ROI, and tau spread fastest in unimpaired and MCI participants. Most amyloid-positive participants followed Braak staging, with substantial regional heterogeneity within each stage.

Direction is for regional tau burden: more tau went with less glucose metabolism (r = -0.49) and with worse domain-specific cognition, while amyloid was diffuse and only weakly related. An imaging association, not an exposure effect.

Direction is for going undiagnosed. Whether the diagnosis itself would change survival is not tested here.

Neither the combined package nor risk-factor modification beat health advice.

Which intervention helped depended on severity: stimulation for cognition at any severity, training for global cognition in mild dementia, rehabilitation for function in mild dementia and for carer burden. Heterogeneity was high.

The association was strongest at moderate intake rather than the highest.

882 cases across five quintiles and several interaction strata, so the subgroup estimates rest on small numbers.

The association is reported in people who already have elevated Alzheimer's blood markers, which is the point of the study.

Direction is for a healthier plant-based diet: higher overall and healthful plant-based diet scores were associated with lower dementia risk, while a higher unhealthful plant-based diet score was associated with higher risk (pooled HR 1.42).

Independent 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.

Pooled observational studies only.

The control arm also received diet counselling and mild caloric restriction, so this is MIND against another active diet, not against usual eating. It is the only randomised test of the MIND diet here and it disagrees with the cohort evidence.

Observational. Points the opposite way to the randomised MIND diet trial.

Significant on one adherence score (MEDAS, HR 0.77) but not the other (PYRAMID, HR 0.86, 95% CI 0.73-1.02).

Controls declined while the olive-oil arm held steady; the nut arm fell between the two. Cognitive follow-up was available for 334 of 447 enrolled.

In dementia there may be small-to-moderate benefits at six months (low-certainty evidence, I2 88-96%); in MCI ginkgo probably has little or no effect (moderate certainty); in subjective cognitive complaints the effect is very uncertain. Adverse events were similar to placebo.

The control arm also received diet counselling and mild caloric restriction, so this is MIND against another active diet, not against usual eating. It is the only randomised test of the MIND diet here and it disagrees with the cohort evidence.

Observational. Points the opposite way to the randomised MIND diet trial.

Pooled observational studies only.

Significant on one adherence score (MEDAS, HR 0.77) but not the other (PYRAMID, HR 0.86, 95% CI 0.73-1.02).

Controls declined while the olive-oil arm held steady; the nut arm fell between the two. Cognitive follow-up was available for 334 of 447 enrolled.

Risk ratios close to one across every intake strategy, including substituting fish for meat. This is the one study here that emulates a trial rather than comparing eaters with non-eaters, and it disagrees with the pooled cohorts.

The biochemical primary outcome was met (DHA raised the CSF DHA-to-arachidonic-acid ratio versus placebo), but there was no difference in cognition or brain volume over 24 months. The authors recommend against further supplementation trials of this kind.

Dietary intake and blood levels, pooled from observational cohorts. The much larger supplement estimate (HR 0.36) comes from one cohort's self-selected supplement users, not from a trial.

The dementia-only estimate barely cleared significance (HR 1.58, 95% CI 1.003-2.48) and its test for trend did not (P=0.50).

Heterogeneity was extreme (I-squared 97%), so the pooled figure hides large differences between the 10 studies.

518 cases. Replacing 10% of ultra-processed food with minimally processed food was associated with 19% lower risk.

Heterogeneity was high (I-squared 95%). Reaches a firmer conclusion than the earlier BMJ meta-analysis of largely the same literature.

The overall PM2.5 estimate includes no effect (HR 1.04, 95% CI 0.99-1.09). Only the studies that actively assessed everyone for dementia showed a clear effect (HR 1.42, 95% CI 1.00-2.02). Most studies were at high risk of bias.

Dose-response by distance for dementia; no association with Parkinson's disease or multiple sclerosis.

Compared with flexible health advice, not with nothing; both groups improved.

The intervention did not change any brain biomarker trajectory. Participants with lower baseline hippocampal volume did show a greater cognitive benefit.

Both groups improved; the structured programme improved more. The trial compares two active interventions, so there is no untreated comparison.

A small improvement that did not reach significance (adjusted difference 0.06, 95% CI -0.001 to 0.128, p=0.055).

High overall and leisure-time activity were associated with lower dementia risk, but occupational and commuting activity were associated with higher risk. Certainty of evidence was very low to low.

No difference between aerobic training and stretching/balance. Cognition was stable in both arms, but with no non-exercising control the trial cannot say whether either arm helped.

Neither the combined package nor risk-factor modification beat health advice.

Concentrating activity into one or two days worked about as well as spreading it across the week.

Direction 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.

The authors call the association weak (RR 0.97), and it was absent beyond 10 years of follow-up.

Pooled across 29 cohorts. The association weakened to HR 0.85 after maximal confounder adjustment and was not significant for low-intensity activity.

The authors state the association held in longer follow-ups, which is their answer to the reverse-causation objection raised by the Whitehall II cohort.

866 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.

The 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.

Explicitly finds no neuroprotective effect, and attributes the lower risk seen in other cohorts to reverse causation: activity fell in the nine years before diagnosis. This contradicts the pooled cohort evidence.

Pools 27 small trials in people who already have dementia, and reports a much larger effect (SMD 0.69) than the single largest such trial, DAPA, which found none.

The primary cognitive outcome was significantly WORSE in the exercise arm (adjusted difference -1.4, 95% CI -2.6 to -0.2, favouring usual care). The authors conclude the programme does not slow cognitive impairment and treat the difference as of uncertain clinical importance. Fitness did improve. This is the sharpest counterweight to the observational exercise evidence.

The primary outcome did not move between groups. Attention and inhibitory control did improve (SMD 0.43), as did muscular strength.

The authors call the effect small (-0.18 points). Significant in women, not in men, on 91 randomised and 76 completing.

Seven small trials; working memory did not improve (P=0.14).

Direction is for carrying APOE and TREM2 risk variants, which were associated with a significant reduction in amyloid-responsive microglia, read by the authors as a diminished cellular response to amyloid. A tissue result, not a clinical outcome.

Direction is for APOE genotype after 90: ε2 carriers had lower dementia risk, while the ε4 association was not statistically significant. Women and Black participants had higher risk than men and Asian participants. Age-standardised incidence was 116.82 per 1000 person-years.

Direction is for carrying APOE ε4: 10-year dementia risk ratios of 1.59 (Filipino, confidence interval crossing 1) to 1.96 (Japanese), similar across the four groups despite carrier prevalence ranging from 14% to 25%. Not modifiable.

Direction is for each additional ε4 allele: it did not change amyloid-related p-tau217 secretion, but for any given p-tau217 level tau spread faster across connected regions, and the p-tau217 threshold marking early tau-PET increases was 26-76% lower than in non-carriers.

Direction is for carrying the deletion, present in 60% of African American ε4 homozygotes: it reduced the AD odds ratio and delayed onset in ε4/ε4 cases with local African ancestry at APOE, confirmed in All of Us, and it abolishes SPI1 repression at the site.

A descriptive proteomic mapping: APOE-linked protein changes were present before amyloid pathology and stable across age and disease stage, with ε2 tied to cellular-maintenance and anti-inflammatory pathways and ε4 to cell-cycle, oligodendrocyte-precursor and downstream vascular, immune and proteostatic proteins. It estimates no effect on a clinical outcome.

Direction is for the APOE4 allele, whose effect ranged from OR 2.22 in Caribbean-Hispanic to 6.13 in Peruvian/Bolivian participants. The APOE2 allele went the other way (OR 0.81). Not modifiable.

Direction is for APOE ε4 carriage, which strengthened the association between amyloid and plasma p-tau; plasma GFAP strengthened the p-tau-tau PET link mainly in non-carriers, and high GFAP went with faster longitudinal tau accumulation.

Direction is for carrying two APOE4 copies: near-complete penetrance of Alzheimer's biology and earlier symptom onset.

Direction is for carrying APOE*4: the ε3/ε4 odds ratio fell stepwise from 4.54 in East Asian to 3.46 in White, 2.18 in Black and 1.90 in Hispanic individuals; ε2 was protective in White and Black but not Hispanic or East Asian individuals. Not modifiable.

Direction 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.

Direction is for midlife hypertension. Genetic risk for Alzheimer's did not modify it, which the authors read as everyone with hypertension standing to gain from treatment.

Direction is for a high polygenic score (excluding APOE): people in the top decile had a twofold risk of Braak stage >4 tangles and of moderate-to-severe amyloid plaque pathology at death. 91 loci identified, 16 new; 18 further loci await validation.

The intervention-control cognitive difference was statistically significant in the higher-genetic-risk halves and not in the lower halves, but neither genetic score significantly modified the intervention effect overall (P > 0.46); an exploratory sex difference emerged for the Alzheimer score.

A transcriptome-wide association study prioritising nine genes (including BIN1, PTK2B and DMPK) with broadly consistent effects across populations; it reports no effect estimate for any exposure, so no direction is recorded.

Locus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Nine signals (HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1, GFRA1) appeared only in APOE-stratified analyses; DDHD1 was protective in ε4 carriers.

Direction is for a higher polygenic score: each standard deviation raised AD odds 1.14-1.52-fold across European, African American, Caribbean Hispanic and Native American Hispanic groups (1.21-1.65 in replication cohorts), and the score tracked worse cognition, more AD neuropathology, smaller hippocampi and abnormal CSF biomarkers.

Direction is for carrying the risk factors. Which factor mattered most differed by APOE risk group, on 2,065 cases split across 11 factors and three genetic strata, so the subgroup estimates are imprecise.

Locus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. The study reports 14 new loci for clinically diagnosed AD and two from AD-by-proxy.

Locus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. The study reports eight new loci (six ancestry-specific, two trans-ancestry) and nominates eight genes in microglial activation, glutamate production and signalling.

Direction is for a higher integrative polygenic score: dementia hazard rose 1.15-fold per SD in older community-dwelling people independently of APOE, generalising to Europeans, East Asians and memory-clinic patients, and reaching five-fold risk when combined with APOE ε4 in memory-clinic patients. Not modifiable.

Direction is for a higher polygenic score: consistently associated with AD risk, age at onset and CSF biomarkers independently of APOE in Europeans and with AD risk in many other ancestries; a cross-ancestry score with the APOE region improved the association, and the signal weakened as the diagnosis was broadened.

Locus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Beyond APOE, the study reports TREM2 R47H and variants near RAB3B, SPOCK3/ANXA10 and SMAP2, and a gene-based association with GIPR.

Locus-discovery genome-wide association study: it reports which genetic regions reached significance and no effect estimate for any exposure, so no direction is recorded. Two signals at 17p13.2 and 18q21.33 are reported; the authors state that African ancestry at 17p13.2 went with lower AD risk and that overall African ancestry did not differ between cases and controls, without an effect estimate.

Direction is for a higher polygenic risk score: each SD raised the dementia hazard 1.35- to 1.42-fold after adjustment including APOE ε4, and the new scores modestly improved prediction (AUC 74.7% to 75.7-76.1%) while still explaining less risk than APOE. Not modifiable.

Direction is for carrying a higher genetic risk score: risk of AD rose 1.6- to 1.9-fold from the lowest to the highest decile, over and above age and APOE4. The main output is 75 risk loci, 42 new.

The study's own results point different ways: the polygenic score added to APOE for predicting AD/MCI and for progression from amyloid-positive MCI to AD, but amyloid deposition was predicted by APOE alone.

The two kinds of variant point opposite ways: deletions and loss-of-function alleles in ABCA1 and ABCA7 and 22q11.21 deletions raised AD risk, while 22q11.21 duplication lowered it (odds ratio 0.34 at exome-wide significance in replication). Not modifiable.

Direction 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.

Direction is for carrying the rare FN1 variant rs140926439 in APOE ε4 homozygotes: odds of AD 0.29 and onset delayed 3.37 years in the 7185-person validation cohort, with zebrafish work suggesting fibronectin loss of function reduces gliosis. Not modifiable.

Direction is for carrying the African ancestry-specific APOE R145C variant with an ε3/ε4 genotype: three-fold higher odds of AD and onset about six years earlier in the discovery stage, replicated in stage 2 and concordant in stage 3. Not modifiable.

A single case report: one man with the PSEN1 E280A mutation stayed cognitively intact until 67 despite very heavy amyloid, and carried a gain-of-function RELN variant. With one case and no comparison group beyond the earlier Christchurch case, no direction can be recorded.

Among 37 heterozygous carriers (ages 56.6-82.1) none had developed AD or MCI by the March 2022 data freeze and apolipoprotein B was lower than in non-carriers, but the authors say continued follow-up is necessary and no homozygotes were found, so protection could not be tested. No incidence comparison is reported, so no direction is recorded.

Direction is for carrying TREM2 T96K: it increased AD risk in family-based and case-control sequencing data and, despite being a gain-of-function variant, impaired microglial clustering around plaques, amyloid uptake and the transition to disease-associated microglia in female 5xFAD mice.

Direction is for carrying the risk variants: R62H and T96K caused excessive skipping of exon 2 and overproduction of a potentially antagonistic TREM2 isoform, and several early-onset dementia variants acted primarily through splicing defects. A molecular mechanism result, not a clinical outcome.

Confined to people who said the aid actually improved their hearing (HR 0.86); those reporting poor improvement showed nothing (HR 0.98).

Direction is for having the impairment. Dual sensory impairment carried the highest risk (HR 1.63 for all-cause dementia, 2.55 for Alzheimer's).

Direction is for hearing loss. Risk was lower among those using hearing aids (aHR 1.06) than those not (aHR 1.20). The authors note their estimates are smaller than earlier studies'.

Null in the primary analysis of the whole cohort. The prespecified analysis of the higher-risk ARIC subgroup found less decline, which the authors present as hypothesis-generating rather than as a result.

Mostly observational (25 of 31 studies), so people who take up hearing aids may differ from those who do not. The authors call for randomised trials — and ACHIEVE, the trial that followed, was null overall.

Against untreated cataract. People who had surgery ended up at about the same risk as controls who never had cataracts (HR 0.84, 95% CI 0.66-1.06), and there was no short-term gain in those already cognitively impaired.

Direction is for having a vision impairment. Single vision impairment raised all-cause dementia risk but not Alzheimer's specifically; having both hearing and vision impairment carried the highest risk.

Direction is for having cataracts or myopia. A Mendelian randomisation analysis supported the cataract-vascular dementia link.

A narrative review arguing that Alzheimer's disease is a brain-specific form of diabetes; it states that type 2 diabetes alone "fall[s] far short of mimicking AD" and reports no effect estimate.

Direction is for midlife hypertension. Genetic risk for Alzheimer's did not modify it, which the authors read as everyone with hypertension standing to gain from treatment.

Regression 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.

Regression discontinuity across the 2 September 1933 eligibility threshold; stronger in women than men.

Pooled observational studies, so open to the confounding the natural-experiment studies were designed to avoid.

Direction is for a hospital-treated infection: the raised dementia hazard (1.54) was barely attenuated by adjustment for frailty (1.49) and persisted among non-frail participants (1.34), so pre-existing frailty and comorbidity did not explain it.

Direction is for delirium on admission: it raised the risk of incident dementia across the whole spectrum of long-term conditions, with the largest relative risk (3.38) in people without multiple long-term conditions.

One of the largest effect sizes in this table (subdistribution HR 3.00), rising about 20% with each further episode. The authors argue for a causal reading.

Read with care: the authors' own reading is that a fall flags undetected dementia rather than causing it, and they recommend cognitive screening after a fall. A one-year window cannot separate cause from early sign.

Direction is for antisense oligonucleotides lowering APP in neurons derived from people with an APP duplication or trisomy 21: reduced APP, rescued endolysosome and autophagy dysfunction and fewer intracellular and extracellular amyloid-β aggregates. Cell-culture work with no human outcome.

A retraction notice. It withdraws the 2006 Nature paper on Aβ*56 over figures showing "signs of excessive manipulation, including splicing, duplication and the use of an eraser tool", and reports no effect estimate.

An investigative news feature reporting signs of image fabrication in papers on the Aβ*56 amyloid oligomer. It is not a study of an outcome and reports no effect estimate.

A perspective review of arguments for and against the amyloid hypothesis, concluding that amyloid-beta is likely necessary but not sufficient and acts early as a trigger of tau-mediated neurodegeneration. It reports no effect estimate.

Phase 1 target-engagement result in 19 people; no clinical outcome measured.

The review's subject is the harm itself: brain swelling and microbleeds caused by the drugs.

Prespecified and post hoc re-analyses of a trial already reported elsewhere, so this is not independent evidence.

A statistically detectable but very small cognitive effect (ADAS-Cog SMD -0.11) alongside 107 more cases of ARIA-E per 1,000. The reviewers' own conclusion is that removing amyloid does not seem to produce clinically meaningful effects — the sharpest disagreement in this table with how the individual trials were reported.

Mechanistic multi-omic profiling of blood from three ARIA-positive patients and three matched controls on lecanemab. It describes a clonally expanded cytotoxic CD8+ T-cell signature and estimates no clinical effect.

Direction is for lecanemab in mice: it significantly reduced amyloid pathology and neuritic damage, an effect absent with Fc-silenced antibody or without microglia despite intact plaque binding. Mouse work with no human outcome.

An initial negative opinion was reversed on re-examination, with use restricted to APOE4 heterozygotes and non-carriers. The EPAR describes ARIA as affecting more than 1 in 10 people without giving a percentage.

Phase Ib/IIa biomarker result in 13 people; no cognitive outcome measured.

Against placebo: ARIA-E 24.4% vs 1.9%. Risk tracks APOE4 status and baseline imaging.

Direction is for the slower titration schedule against standard dosing, on the drug's own side effect. Amyloid reduction was comparable.

An open-label extension: after 18 months everyone is on the drug, so the comparison is early-start versus delayed-start, not drug versus placebo.

A single-clinic safety series with no comparison group. It reports how often ARIA and infusion reactions happened in practice, which is useful, but it cannot estimate an effect of the drug in either direction.

A mechanistic tissue study describing which microglial states accompany amyloid removal (TREM2 and APOE upregulation correlating with antibody response and clearance; complement signalling contributing). It estimates no effect of immunisation on a clinical outcome.

Corporate announcement discontinuing a product and terminating its confirmatory trial. It reports no clinical outcome, so no direction exists to record.

CHMP refused the drug, then on re-examination recommended it only for people with one or no APOE4 copy, where the ARIA rates are lower. Benefit on cognition and harm from ARIA in the same document, with the restriction as the regulator's way of balancing them.

Benefits were statistically present but every one fell below the minimum clinically important difference, against a number needed to harm of 9 for ARIA-oedema. Agrees with the Cochrane review and not with the trial reports.

Approved on amyloid reduction (surrogate) while reporting higher ARIA rates than placebo; the notice reports no cognitive outcome.

Less decline than placebo, alongside infusion reactions and ARIA.

Phase 1 dose-finding. The outcome is amyloid clearance; no cognitive outcome was measured.

Two identically designed trials disagreed: EMERGE met its primary endpoint, ENGAGE did not.

A coverage determination. It sets the conditions under which Medicare pays and reports no effect estimate.

Benefit is on the surrogate marker only: the approval rested on amyloid reduction, not on confirmed clinical benefit, and the confirmatory trial was later terminated.

Co-primary endpoints were not met at 52 weeks. The comparator was a low dose of the same drug rather than placebo, which the authors say masked any separation; they report separation in the MCI subgroup only at 78 and 104 weeks.

The primary endpoint was not met: the low dose showed no clinically meaningful benefit and the 3 mg dose showed 32% greater progression than placebo, with more serious adverse events. Less whole-brain volume loss on MRI is a surrogate finding.

The primary clinical endpoint (CDR-SB) was not met in the overall population. The tau figures are a biomarker outcome, not a clinical one.

ADAS-Cog11 showed slower decline, but the co-primary functional endpoint (ADCS-ADL) did not differ and the authors classify the study as negative.

Phase 1b safety and target-engagement result: adverse events were all mild or moderate with no serious events on MAPTRx, and CSF total tau fell dose-dependently by more than 50% in the two highest-dose groups. No clinical outcome was measured.

Antihypertensive treatment improved cognitive scores by a small amount (SMD 0.06, moderate certainty) but the reduction in dementia incidence was not statistically significant (OR 0.89, low certainty). The drug-class rankings rest on one trial per class and are described as highly uncertain.

Significant for MCI and for the MCI-or-dementia composite; not significant for probable dementia alone (HR 0.86, 95% CI 0.72-1.02).

A large drop in blood pressure (22/9 mmHg) and fewer serious adverse events in the intervention villages.

Antihypertensive use tracked lower Alzheimer's risk but not lower non-Alzheimer dementia risk, where treated and untreated hypertension looked the same. A single baseline blood pressure reading predicted neither.

Individual participant data from five double-blind placebo-controlled trials, which is the strongest design in this table for this exposure.

Consistent across 14 trials (I-squared 0%) but small in absolute terms: 0.39 percentage points over about 4 years.

Direction is for STOPPING the antipsychotic: discontinuers were hospitalised less than matched continuers.

Direction 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.

Wider range of harms than regulatory alerts had flagged, with the highest risks soon after starting. No increase in ventricular arrhythmia.

Direction is for valacyclovir: cognition worsened more on the drug than on placebo on the primary outcome (between-group difference 3.93 ADAS-Cog points, P = .01); function, amyloid PET and tau PET did not differ. The authors conclude it is not recommended.

No difference from placebo on the primary agitation outcome or other main behavioural outcomes. As-needed psychotropic use was lower during the active period, and no serious drug-related adverse events occurred.

Observational: 80% of residents were on no anti-dementia drug, so who gets prescribed and who does not may itself track prognosis.

Cholinesterase 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.

The authors state the data are compatible with anything from a 39% decrease to a 5% increase in risk, against DPP-4 inhibitors rather than no treatment.

For GLP-1 receptor agonists specifically: HR 0.95 (95% CI 0.87-1.04) against DPP4 inhibitors in the intention-to-treat analysis. Only the continuous-use analysis reached significance (HR 0.79).

Seven separate comparisons against seven other antidiabetic drugs, so the comparator is always another drug rather than no treatment.

Primary outcome null. One secondary cognitive measure (ADAS-Exec) favoured liraglutide on an unadjusted test; ADCS-ADL and CDR-SB did not.

Direction is for AAVrh.10 delivery of APOE2 with the Christchurch mutation in mice: both vectors suppressed amyloid, but only the Christchurch variant also suppressed tau tangles and glial activation in tau mice and outperformed plain APOE2 behaviourally. Mouse work with no human outcome.

Heterogeneity was near-total (I-squared 98.9%) and the estimate went to null in people newly diagnosed with diabetes (HR 1.01), which is where prevalent-user bias would be smallest.

Designed around new diabetes diagnoses with a landmark analysis and a one-year lag, which removes the prevalent-user advantage that inflates metformin's apparent benefit in the pooled cohorts.

Comparator is other oral antidiabetic drugs, not no treatment.

The split inside this one paper is the finding: the 41 observational studies show large benefits (SGLT2i OR 0.56, GLP-1RA OR 0.58) while the 23 randomised trials show no difference. When design and result disagree this cleanly, the trials are the ones to believe.

The 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.

Direction is for peripheral cancer in AD mice: tumour-secreted cystatin-C bound amyloid oligomers and activated microglial TREM2, enabling degradation of existing plaques and rescuing cognition; the effect was abolished by microglial deletion or mutation of TREM2 or cystatin-C. Mouse work with no human outcome.

Direction is for lowering PU.1 in microglia, which reduced the severity of amyloid pathology in mice; microglia-specific CD28 deficiency did the opposite and increased plaque load. Mouse work with no human outcome.

A descriptive transcriptional atlas: it maps expression changes, isoform usage, co-expression modules and disease subtypes in microglia from post-mortem brains and estimates no effect of an exposure.

Direction is for deleting TIM-3 in microglia: it increased phagocytic activity, shifted microglia to the disease-associated state, reduced amyloid pathology and improved cognitive impairment in 5xFAD mice. Mouse work with no human outcome.

Direction is for blocking the ZBP1-RIPK1 axis: genetic deletion of Zbp1 or inhibition of RIPK1 attenuated neuroinflammation, amyloid pathology and behavioural deficits in AD mice, after showing that amyloid-induced oxidised mitochondrial DNA forms Z-DNA sensed by ZBP1 in microglia. Mouse work with no human outcome.

Direction is for removing the granzyme K-producing CD103-negative CD8+ T cells: their ablation ameliorated cognitive decline and reduced neuropathology in 3xTg-AD mice, and granzyme K caused neuronal dysfunction and tau hyperphosphorylation via PAR-1. Mouse and cell work with no human outcome.

Direction is for inhibiting C1q, C3 or the microglial receptor CR3, which reduced phagocytic microglia and early synapse loss; C1q was necessary for soluble amyloid-beta oligomers to damage synapses. Mouse work with no human outcome.

Direction is for NLRP3 or caspase-1 deficiency, which largely protected the mice from spatial memory loss and reduced amyloid deposition; the human data are limited to raised active caspase-1 in post-mortem MCI and Alzheimer brains.

The trial did not meet its primary endpoint at any of three doses despite sustained target engagement (lower CSF soluble TREM2, higher osteopontin); the most frequent adverse events were MRI changes resembling ARIA.

A regulatory enforcement action, not a study. The SEC's order finds the reported Phase 2 biomarker data were manipulated by an unblinded consultant and its complaint alleges the full patient data "showed no measurable cognitive improvement in the patients' episodic memory"; it estimates no effect.

Retraction notices for five PLOS ONE papers by Wang and colleagues, two co-authored with a Cassava Sciences employee. They withdraw the papers over blot-image integrity and estimate no effect.

The NPI-C agitation/aggression measure did not reach significance (p=0.094).

Not effective, and drug-related QT prolongation was observed. The randomised sample was smaller than planned.

A feasibility trial in 29 residents: designed to test whether the trial can be run, not powered for efficacy, and it reports no efficacy estimate.

The authors describe the reduction as small (-1.32 points).

A post hoc dementia subgroup of a randomised-withdrawal trial that was not designed or powered for it; 46 randomised responders. The authors say to read it cautiously.

Both doses beat placebo. Treatment-emergent adverse events were more common than placebo (84.6% at 2 mg, 76.8% at 1 mg, 73.8% placebo).

For SGLT2 inhibitors specifically: HR 0.86 (95% CI 0.79-0.94) against DPP4 inhibitors, and HR 0.70 in the as-treated analysis.

After the first year the data rule out more than a 3% change either way. Diagnoses were 46% higher in the first year, which the authors attribute to people being seen more often just after starting a statin. This sits against the Chicago cohort, which found benefit in APOE4 carriers.

Benefit 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.

A mechanism study: it shows Arc packages tau into extracellular vesicles and that cell-to-cell tau transmission is almost absent in Arc knockout mice, with Arc levels correlating with phosphorylated tau in human AD brain vesicles. It tests no intervention and estimates no effect on an outcome.

Direction is for tau seeding activity: substantial hippocampal and neocortical seeding was present even without overt neocortical tangles and predicted region-specific cognitive performance and longitudinal decline; seeding and modification profiles tracked neuritic plaque density and separated AD from PART.

A model-building and screening study: it identifies over 500 genetic modifiers of tau propagation (including VPS29 and the UFMylation cascade) and shows UFMylation inhibition suppresses seeded propagation in vitro and in vivo. It estimates no effect on a clinical outcome.

The authors read these symptoms as early markers of neurodegeneration rather than causes — which is also how an earlier analysis of this same cohort read its own null result for midlife depression.

Direction is for having depression (51% higher risk). Treated depression carried lower risk than untreated (HR 0.7), which is the more interesting half but is an observational comparison of people who did and did not get treatment.

Midlife depressive symptoms did not raise dementia risk (HR 1.21, 95% CI 0.95-1.54), even when chronic. The association closer to diagnosis is read by the authors as depression being a prodromal feature, not a cause.

Direction 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.

Education and job complexity each contributed independently; about 28% of the education effect ran through occupation.

Effect held over and above measured Alzheimer's pathology, which is the point of the reserve idea.

Distress rose, and rose most in APOE4 homozygotes. The authors nonetheless conclude disclosure by a trained provider was generally safe and well tolerated in this psychologically pre-screened group.

Neither choir singing nor group music therapy beat standard care. Country was the strongest predictor of the differences between sites.