[O4–07–02]: LOWER WHITE MATTER INTEGRITY IS ASSOCIATED WITH HIGHER AMYLOID DEPOSITION AND RETROSPECTIVE COGNITIVE DECLINE IN OLDER ADULTS WITHOUT DEMENTIA

The accumulation of beta-amyloid (Aβ), a pathological hallmark of Alzheimer's disease (AD), is highly age-related and regionally selective, while the causal factors of age-relatedness and regional selectivity remain largely unknown. Abnormality of white matter (WM) tracts is very common in clinically normal older adults and has been associated with an increased risk of developing AD. In this study, we examined the association between white matter integrity, amyloid accumulation, and retrospective cognitive trajectories among older adults without dementia. One hundred twenty-five nondemented, ethnically diverse, and community-dwelling older adults from the Washington Heights-Inwood Columbia Aging Project (WHICAP) underwent 18F-Florbetaben amyloid PET and diffusion-weighted scans that quantify brain amyloid burden and WM tract integrity, respectively. All subjects were longitudinally followed for cognitive assessment prior to imaging. A global amyloid index was calculated by standardized uptake value ratio (SUVR) with a cerebellar gray matter reference region and Aβ positivity cutoff was determined using a K-means clustering method, which classified 91 subjects as “Amyloid-negative (Aβ− O)” and 34 as “Amyloid-positive (Aβ+ O)”. We found significant interactions between axial diffusivity of superior longitudinal fasciculus and the body of corpus callosum (higher values indicating lower WM integrity) and amyloid group showing that lower WM integrity is associated with increased level of mean cortical Aβ deposition, accounting for age and sex (ps < 0.05) among Aβ+ O group but not within Aβ− O group. Aβ positivity status and lower WM integrity were associated with retrospective cognitive decline in processing speed, while there was no interaction effect of Aβ pathology and WM integrity in predicting retrospective cognitive changes. Neither APOE4 carrier status nor cross-sectional cognitive measures was associated with WM integrity. Lower white matter microstructure integrity is a strong correlate of amyloid deposition and reflects retrospective decline in processing speed among older adults without dementia. Future studies are warranted to determine a directionality of this relationship using longitudinal assessments.