Midlife Blood Pressure, Plasma β-Amyloid, and the Risk for Alzheimer Disease The Honolulu Asia Aging Study

beta-Amyloid (A beta), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer disease (AD) and possibly vascular dementia. We investigated the joint association of midlife BP and A beta peptide levels with the risk for late-life AD and vascular dementia. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965-2000). Midlife BP was measured starting in 1971 in participants with a mean age of 58 years; A beta was measured in specimens collected in 1980-1982, and assessment of dementia and autopsy collection started in 1991-1993. The outcome measures were prevalent (present in 1991-1993) and incident AD (n=53, including 38 with no contributing cardiovascular disease) and vascular dementia (n=24). Cerebral amyloid angiopathy, beta-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in postmortem tissue. The risk for AD significantly increased with lower levels of plasma A beta (A beta 1-40 hazard ratio: 2.1 [95% CI: 1.4 to 3.1]; A beta 1-42 hazard ratio: 1.6 [95% CI: 1.1 to 2.3]). Evidence of interaction between diastolic BP and plasma A beta (1-40 P-interaction <0.05; 1-42 P-interaction <0.07) levels indicated that the A beta-related risk for AD was higher when BP was higher. Low plasma A beta was associated with the presence of cerebral amyloid angiopathy (P-trend<0.05) but not the other neuropathologies. A beta plasma levels start decreasing >15 years before AD is diagnosed, and the association of A beta to AD is modulated by midlife diastolic BP. Elevated BP may compromise vascular integrity leading to cerebral amyloid angiopathy and impaired A beta clearance from the brain. (Hypertension. 2012;59:780-786.). Online Data Supplement