a prospective case-cohort study

Summary Background Amyloid β peptides (Aβ) are important components of plaques in Alzheimer’s disease. Plasma concentrations of Aβ1–40 and Aβ1–42 rise with age and are increased in people with mutations that cause early-onset Alzheimer’s disease. However, Aβ1–42 concentrations may decrease early in the dementia process. We postulated that concentrations of Aβ1–40 and Aβ1–42 in plasma are associated with risk of dementia. Methods We did a case-cohort study embedded in the prospective, population-based Rotterdam Study. Of 6713 participants at risk for dementia, a random sample of 1756 people was drawn. During follow-up (mean 8·6 years), 392 incident dementia cases were identifi ed. We investigated the association between plasma Aβ concentrations and risk of dementia and its subtypes using Cox proportional hazard models. Findings High concentrations of Aβ1–40 but not Aβ1–42 at baseline were associated with an increased risk of dementia. Compared with the fi rst quartile of Aβ1–40, age and sex-adjusted hazard ratios for dementia for the second, third, and fourth quartiles were 1·07 (95% CI 0·72–1·58), 1·16 (0·78–1·70), and 1·46 (1·01–2·12). People with an increased Aβ1–42/Aβ1–40 ratio had a reduced risk of dementia. Compared with the fi rst quartile of the Aβ1–42/Aβ1–40 ratio, hazard ratios for the second, third, and fourth quartiles were 0·74 (0·53–1·02), 0·62 (0·44–0·88), and 0·47 (0·33–0·67). Associations were similar for Alzheimer’s disease and vascular dementia.