Hypertension and obesity moderate the relationship between β‐amyloid and cognitive decline in midlife

Abstract Background This study tested if central obesity, hypertension, or depressive symptoms moderated the relationship between β‐amyloid (Aβ) and longitudinal cognitive performance in late middle‐aged adults enriched for Alzheimer's disease (AD) risk. Methods Participants ( n = 207; ages = 40–70 years; 73% parental AD) in the Wisconsin Registry for Alzheimer's Prevention study completed 3+ neuropsychological evaluations and a [ 11 C]PiB positron emission tomography scan or lumbar puncture. Linear mixed‐effects regression models tested interactions of risk factor × Aβ × visit age on longitudinal Verbal Learning & Memory and Speed & Flexibility factor scores. Results The relationship between Aβ and Verbal Learning & Memory decline was moderated by hypertension ( χ 2 (1) = 3.85, P = .04) and obesity ( χ 2 (1) = 6.12, P = .01); those with both elevated Aβ and the risk factor declined at faster rates than those with only elevated Aβ or elevated risk factors. Conclusion In this cohort, hypertension and obesity moderated the relationship between Aβ and cognitive decline.