Background  Plasma levels of amyloid β peptide (Aβ) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk.

Objective  To relate midlife plasma Aβ measures and 10-year change in plasma Aβ measures since midlife to late-life cognitive decline.

Design  Prospective study of a population-based sample.

Setting  Academic research.

Participants  Plasma Aβ40 and Aβ42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Aβ40 to Aβ42 ratios and Aβ42 levels to late-life cognitive decline, as well as relations of 10-year change in Aβ40 to Aβ42 ratios and Aβ42 levels to cognitive decline.

Main Outcome Measures  The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall.

Results  Higher midlife plasma Aβ40 to Aβ42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Aβ40 to Aβ42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Aβ42 levels alone or with change in Aβ42 levels since midlife.

Conclusion  In this large community-dwelling sample, higher plasma Aβ40 to Aβ42 ratios in late midlife and increases in Aβ40 to Aβ42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.

Author Affiliations: Division of Aging and Channing Laboratory, Department of Medicine (Drs Okereke and Grodstein), and Center for Neurologic Diseases, Department of Neurology (Drs Xia and Selkoe), Brigham and Women's Hospital and Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health (Dr Grodstein), Boston, Massachusetts.