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MIDLIFE AMYLOID, TAU, CEREBROVASCULAR DISEASE, AND NEURODEGENERATION PROFILES IN A RACIALLY/ETHNICALLY-DIVERSE, COMMUNITY-BASED COHORT
Abstract
Aims
The amyloid-tau-neurodegeneration (AT(N)) Alzheimer’s disease (AD) research framework has been increasingly expanded to include other biomarkers, such as cerebrovascular disease (V). We characterized cortical thickness by ATV profiles in a racially and ethnically diverse, middle-aged community-based cohort.
Methods
Participants (n=65, age=61±6, sex=68% women, race=11% Non-Latinx White, 25% Non-Latinx Black, 64% Latinx, APOE4=32% carriers) were from the Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease. Amyloid and tau positivity were determined in Thal and Braak regions, respectively; 2SD above the mean was used as the positivity threshold. Total white matter hyperintensity volume, representing ischemic small vessel disease, was the primary marker of cerebrovascular disease; the median volume was used as the positivity threshold. Cortical thickness in the AD signature was compared across ATV profiles.
Results
Half (48%) of middle-aged adults had no pathology (A-T-V-) based on our positivity thresholds, 37% had vascular pathology only (A-T-V+), 5% had AD pathology only (A+T-V-, A+T+V-), 9% had both AD and vascular pathology (A+T-V+, A+T+V+), and one person had non-AD and vascular pathology (A-T+V+; excluded from subsequent analyses). Compared to those with no pathology, AD signature was numerically lower in those with vascular pathology only (-0.01 [-0.06, 0.04]) and in those with AD pathology with and without vascular pathology (-0.03 [-0.10, 0.03]).
Conclusions
Cerebrovascular pathology was the most common midlife pathology. AD without cerebrovascular pathology was less common than AD with cerebrovascular pathology. Progressive ATV profiles were descriptively related to lower cortical thickness, but should be confirmed as more participants are imaged.