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

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.

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. 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.

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.

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 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. 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. 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. 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 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.

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 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.

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.

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. 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.

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.

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.