PT  - JOURNAL ARTICLE
AU  - Sullivan, Kevin J.
AU  - Blackshear, Chad
AU  - Simino, Jeannette
AU  - Tin, Adrienne
AU  - Walker, Keenan A.
AU  - Sharrett, A. Richey
AU  - Younkin, Steven
AU  - Gottesman, Rebecca F.
AU  - Mielke, Michelle M.
AU  - Knopman, David
AU  - Windham, B. Gwen
AU  - Griswold, Michael E.
AU  - Mosley, Thomas H.
TI  - Association of Midlife Plasma Amyloid-β Levels With Cognitive Impairment in Late Life
AID  - 10.1212/WNL.0000000000012482
DP  - 2021 Sep 14
TA  - Neurology
PG  - e1123--e1131
VI  - 97
IP  - 11
4099  - http://n.neurology.org/content/97/11/e1123.short
4100  - http://n.neurology.org/content/97/11/e1123.full
SO  - Neurology2021 Sep 14; 97
AB  - Background and Objectives To evaluate the association between midlife plasma amyloid-β (Aβ1-42, Aβ1-40, Aβ42:Aβ40) and risk of mild cognitive impairment (MCI) and dementia.Methods Plasma Aβ42 and Aβ40 were retrospectively measured with a fluorometric bead-based immunoassay in a subsample of the Atherosclerosis Risk in Communities cohort study. We investigated the relationship of plasma Aβ42, Aβ40, and Aβ42:Aβ40 ratio measured in midlife and late life and the change from midlife to late life to risk of MCI, dementia, and combined MCI/dementia outcomes in late life (from 2011–2019). We used multinomial logistic regressions estimating relative risk ratios (RRRs) of these cognitive outcomes vs cognitively normal adjusted for age, sex, education, site-race, APOE, hypertension, diabetes, and body mass index.Results A total of 2,284 participants were included (midlife mean age 59.2 ± 5.2, 57% female, 22% Black). Each doubling of midlife Aβ42:Aβ40 was associated with 37% lower risk of MCI/dementia (RRR 0.63, 95% confidence interval [CI] 0.46–0.87), but only up to approximately the median (spline model threshold 0.20). Every 1-SD increase in plasma Aβ42 (10 pg/mL) was associated with 13% lower risk of MCI/dementia (RRR 0.87, 95% CI 0.77–0.98), whereas every 1-SD increase in plasma Aβ40 (67 pg/mL) was associated with 15% higher risk of MCI/dementia (RRR 1.15, 95% CI 1.01–1.29). Associations were comparable but slightly weaker statistically when models were repeated using late-life plasma Aβ predictors. Aβ42 and Aβ40 increased from midlife to late life, but changes were not associated with cognitive outcomes.Discussion Midlife measurement of plasma Aβ may have utility as a blood-based biomarker indicative of risk for future cognitive impairment.Aβ=amyloid-β; AD=Alzheimer disease; ARIC=Atherosclerosis Risk in Communities; BMI=body mass index; CI=confidence interval; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; RRR=relative risk ratio