Midlife Blood Pressure, Amyloid-β, and Risk for Alzheimer Disease

Abstract

See related article, pp 780–786 The association between hypertension and vascular dementia (VaD) is well established and biologically plausible. Hypertension and small vessel disease are common in vascular cognitive impairment.1 The relatively more recent discovery that hypertension is associated with increased risk of Alzheimer disease (AD) is less intuitively understandable, and so the search for mechanisms continues. Recognizing that sensitivity may be preferred to specificity in the early stages of seeking to identify plausible mechanisms, the report by Shah et al2 in this issue of Hypertension takes an important step in this direction. Using a prospective design, these investigators examined the association between midlife blood pressure (BP) and amyloid-β (Aβ) peptide levels and risk for late-life AD and VaD in 667 Japanese-American men participating in the Honolulu Asia Aging Study. Data for the analyses were taken from 7 examinations, ≈3 years apart beginning between 1965 and 1967 and ending in 2000. The outcome measures were prevalent and incident AD (with and without contributing cardiovascular disease), pure AD (n=38), and VaD (n=24). Cerebral amyloid angiopathy (CAA), Aβ neuritic plaques, and neurofibrillary tangles were evaluated postmortem in a subsample of 73 men. Midlife BP was not associated with prevalence or incidence of VaD. However, for the all-AD outcome category there was an interaction between diastolic BP and plasma Aβ measures for prevalent AD. Estimated risk for late-life dementia for every 1-SD decrease in plasma Aβ at midlife was higher for diastolic hypertensive individuals (BP ≥90 mm Hg) than for persons with low diastolic BP (≤80 mm Hg) for both Aβ1–40 and Aβ1–42 assays. …