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

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 [11C]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 (χ2(1) = 3.85, P = .04) and obesity (χ2(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.