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.

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 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. 39 candidate factors were screened against 485 cases, so individual estimates are imprecise.

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 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.

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 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 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 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.

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 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.

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.

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.

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 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 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 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.

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).

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

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).

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

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

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 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 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 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.

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.

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 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'.