Every row of the evidence table

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Two findings point opposite ways: synchronised norepinephrine, blood-volume and CSF oscillations during natural NREM sleep were the strongest predictors of glymphatic clearance, while the sleep aid zolpidem suppressed those oscillations and glymphatic flow. Mouse work with no human outcome.