Although evidence suggests a relationship between elevated beta-amyloid and cognitive decline, approximately 30% of older adults with positive markers of amyloid remain cognitively healthy. Our objective was to test if the presence of modifiable risk factors (i.e., central obesity, hypertension, and depressive symptoms) moderated the relationship between amyloid and longitudinal cognitive performance. Data were from 207 adults (140 females; age range=40-70) enriched for Alzheimer's disease risk (73% parental history of Alzheimer's disease) enrolled in the Wisconsin Registry for Alzheimer's Prevention study. Participants completed at least three neuropsychological evaluations and one biomarker visit ([C11]Pittsburgh Compound B PET scan or lumbar puncture). Participants were characterized as high or low on beta-amyloid using cutoffs developed for [C11]Pittsburgh Compound B-PET distribution volume ratio or CSF amyloid beta 1-42 values. Participants were also coded as high or low risk on obesity (waist circumference > 102 cm for males or 88 cm for females), hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg), and depressive symptoms (Center for Epidemiologic Studies of Depression scale ≥ 16). Linear mixed effects regression models examined three-way interactions between modifiable risk factor status x beta-amyloid status x visit age on longitudinal Verbal Learning & Memory and Speed & Flexibility factor scores. Results indicated that the relationship between beta-amyloid and Verbal Learning & Memory decline was moderated by the presence of hypertension at baseline (p = .02), presence of hypertension at all visits (p = .001), and presence of obesity at all visits (p = .049). Depressive symptoms did not moderate the association between beta-amyloid and longitudinal Verbal Learning & Memory (p = .62) or Speed & Flexibility (p = .15) performances. In this at-risk for Alzheimer's disease cohort, modifiable risk factors of hypertension and obesity moderated the relationship between beta-amyloid and cognitive decline. Identification and modification of these risk factors in late middle age may slow the effect of amyloid on the progression of cognitive symptoms.

Modifiable risk factors moderate the relationship between amyloid and cognition in midlife