White Matter Microstructure is Associated with Serum Clusterin and Everyday Functioning in a Sample of Nondemented Older Adults

Abstract

Background: Although clusterin-a protein involved in lipid metabolism, amyloid beta clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at risk for Alzheimer’s disease, research exploring associations with white matter (WM) micro- and macro- structural markers are largely limited. Objective:: The current study [1] explored associations between serum clusterin protein levels and WM micro- and macro- structural markers, and [2] clarified whether variations in WM fractional anisotropy (FA) were associated with functional abilities within in a racially homogenous sample of relatively well-educated older adults free of dementia. Methods: Participants underwent magnetic resonance imaging (MRI) brain exams and a blood draw and completed a performance-based measure of everyday functioning. Multiple linear regression adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin associations with WM metrics, as well clarify potential links between WM microstructure and everyday functioning. Results: Higher serum clusterin was associated with lower FA in several thalamocortical (anterior and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02). Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but higher FA of several WM tracts was associated with better performance on the Independent Living Scale (ßs = .37 to .53, ps = .006 to .03). Conclusion: Serum clusterin is differentially associated with WM metrics, and WM microstructure is associated with everyday functioning.