Every row of the evidence table

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.

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.

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.

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 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 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 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 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.

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.

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.

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.

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

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

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.

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 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.

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 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.

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

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.

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.

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).