Every row of the evidence table

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.

Improves depressive symptoms (moderate certainty) and overall behavioural problems (low certainty). No effect on agitation (SMD -0.05, 95% CI -0.27 to 0.17) and no evidence of long-term effects. Sits against the null MIDDEL trial on the same exposure.

Direction is for normal sleep versus sleep deprivation, on a clearance measure — not on cognition, which this trial did not measure.

Eight kinds of sleep disturbance were analysed; both short and long sleep carried higher risk, as did excessive daytime sleepiness and insomnia.

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.

Direction is for LOSING slow-wave sleep. 52 cases in 346 people, so the estimate is imprecise, and slow-wave sleep also falls with Alzheimer's genetic risk, which muddies cause and effect.

No significant association with vascular dementia, and none of the 11 studies used biomarkers to confirm the diagnoses.

Direction is for SHORT sleep (6 hours or less): higher dementia risk than a 7-hour sleep duration.

A narrative review proposing glymphatic failure as a final common pathway to dementia. It reports no effect estimate.

Persisted after controlling for depression and social isolation.

Isolation (being alone) carried the risk (HR 1.26); loneliness (feeling alone) did not once depressive symptoms were accounted for (HR 1.04, 95% CI 0.94-1.16). That split matters, and the loneliness meta-analysis here reaches the opposite conclusion about loneliness.

Significant 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.