Every row of the evidence table

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 chronic kidney disease as a source of false signal: at eGFR 45 versus 60, p-tau217 was 31-55% higher in amyloid-negative people on two immunoassays, a rise largely removed by using the %p-tau217 ratio. A test-validity 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.

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 microglial activation: amyloid was associated with astrocyte reactivity across cortical regions only when microglia were activated, and that microglia-dependent reactivity related to cognitive impairment through tau phosphorylation and aggregation.

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 BEING a carer: carers were worse off than non-carers on every domain, with the largest gaps in depression and stress.

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 on the Alzheimer's continuum: societal costs were 52% higher in subjective cognitive decline, 170% in MCI and 307% in AD dementia than in controls, and payer costs 26%, 85% and 36% higher. 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 living in the community rather than a nursing home: unadjusted costs were lower in the community, but after adjusting for functional impairment and comorbidity community care cost €11,344 more per year, mainly through informal care. A cost result, not a health outcome.

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 value for money at current Australian prices: donanemab improved modelled QALYs (4.38 vs 4.01) but the ICER of $342,424 per QALY exceeded commonly cited willingness-to-pay thresholds. An unfavourable value result, not a clinical harm.

Direction is for value for money: three years of lecanemab gained 0.17 QALYs and the cost-effective price at 1 million SEK per QALY was 33,886 SEK a year, which the authors say makes it unlikely to be cost effective in Sweden at current US list prices. An unfavourable value result, not a clinical harm.

Direction is for value for money at the current price: no lecanemab strategy was cost-effective against standard care alone, whichever diagnostic test was used; CSF-guided targeted treatment would become cost-effective below $5,100 per year. An unfavourable value result, not a clinical harm.

Direction is for chronic bi-weekly intravenous infusion relative to oral treatment: administration and monitoring cost $45,208 plus $6,095 caregiver burden, eroding 44% of treatment value, against 2% for an oral drug. A cost result for a hypothetical treatment, not a clinical harm.

Direction is for value for money at the list price: the benchmark price ($8,900-$21,500 per year) sits below the $26,500 list price, the committee voted 15-0 that the drug represents low long-term value at that price and 12-3 that the evidence did not adequately demonstrate a net health benefit. An unfavourable value assessment, not a clinical harm.

Direction is for value for money at the assumed $28,000 annual price: ICERs of $981,000/QALY (aducanumab) and $193,000/QALY (donanemab) exceed the $150,000/QALY threshold, so neither was cost-effective. An unfavourable value result, not a clinical harm.

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 an older-than-chronological sleep EEG brain age: each 10-year increase in the index was associated with a 39% higher risk of incident dementia, consistent across sex and age groups.

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 regional tau burden: more tau went with less glucose metabolism (r = -0.49) and with worse domain-specific cognition, while amyloid was diffuse and only weakly related. An imaging association, not an exposure effect.

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