A-100: Psychological Well-Being Moderates Associations Between Vascular Risk Burden and Alzheimer’s Disease Neuropathology

Abstract

Objective: Vascular risk burden (VRB) influences Alzheimer’s disease (AD) through biological, behavioral, and psychosocial pathways. Psychological well-being (PWB), a multidimensional construct of positive psychological functioning, is independently linked to VRB and resilience in brain aging. However, less is known about whether these factors operate jointly or whether PWB influences associations between VRB and neuropathology. This study examined whether PWB moderates the relationship between VRB and AD neuropathology, hypothesizing that higher PWB would attenuate these associations. Method/Data Selection: Participants were 1,270 autopsied older adults from the Rush Alzheimer’s Disease Consortium (RADC; mean age = 81.17; mean education = 15.19 years; 73.3% female; 19.4% apolipoprotein E ε4 [APOE ε4] carriers). PWB was assessed using Ryff’s 18-item scale. VRB was an ordinal composite of hypertension, diabetes, and smoking history. Outcomes included square-root-transformed β-amyloid (Aβ) and tau neurofibrillary tangles (NFTs). Generalized linear models tested associations and moderation, adjusting for age, sex, education, and APOE ε4 status. Results/Data Synthesis: PWB was not associated with VRB (OR = 0.86, 95% CI [0.68, 1.10]) or Aβ (β = 0.044). Greater VRB was associated with Aβ (β = -0.050, p = .049) and NFTs (β = -0.117, p < .001). The VRB × PWB interaction was not significant for Aβ (β = -0.075, p = .227) but was significant for NFTs (β = -0.184, p = .014), such that VRB was associated with NFTs at mean and high PWB but not at low PWB. Conclusions: PWB moderated the relationship between VRB and NFTs. These findings suggest associations between VRB and NFTs may vary as a function of PWB.