Prospective Change in Preclinical MRI Markers of ADRD Risk and Brain Aging by Race, Socioeconomic Status, and Sex

University Of Maryland Baltimore County, Baltimore MD

Investigators

Linked publications, trials & patents

Abstract

African Americans (AA) and those with low socioeconomic status (SES) are at disproportionate risk for Alzheimer’s disease-associated dementia (AD) and related dementias (ADRD). It is crucial to understand (a) differential prospective relations of race, adult SES, and their interaction with one another (or with biological sex) with change in previously established, magnetic resonance imaging (MRI) assessed, preclinical markers of early AD/ADRD risk and accelerated brain aging; (b) their biopsychosocial mediators; and (c) their relation to cognitive decline. Linked to the ongoing Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort study, our ancillary HANDLS Scan substudy showed synergistic relations of race and SES to brain volumes and white matter (WM) disease. Low SES conferred the greatest disadvantage to AAs for WM lesion burden; and higher SES conferred substantial advantage to Whites, but not AAs, for global and regional brain volumes. Lower SES, AA race, and/or their interaction were also related to lesser WM integrity, and diminished resting state connectivity in frontal and default mode networks. Further, race and/or SES subgroups displayed differential vulnerability to the relations of select biopsychosocial risk factors (e.g., diabetes, diet quality) to poor brain and cognitive outcomes. To expand upon these important cross-sectional findings, we propose a prospective follow-up of the 238 stroke-and dementia- free HANDLS Scan participants (42% AAs, 49% low SES, 55% women, mean age = 52 at baseline) to assess 8-10 year change in MRI markers of AD/ADRD risk and accelerated brain aging, identify multi-level mediators of such change, and their covariation with cognitive decline. Specifically, we will: (1) examine interactive relations of race, SES (and sex) with (a) prospective change in previously identified MRI-based summary indices reflecting AD-like atrophy patterns [Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s Disease (SPARE-AD)]; accelerated brain aging-related atrophy patterns [Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA)]; data-driven components of regional WM lesions to assess location- specific burden of small vessel disease; cerebral blood flow, and structural and functional connectivity; (2) examine biopsychosocial mediators of these relations, and longitudinal covariation with cognitive function; and (3) apply multi-modal data fusion across structural MRI, diffusion tensor imaging, arterial spin labeling, and resting state fMRI to characterize race by SES (and race by sex) brain structure-function relations at baseline, and utilize the overall summary indices as predictors of sociodemographic variation in follow-up measures of SPARE-AD, SPARE-BA, and frontal WMLV and cognitive decline. Understanding the differential patterns, multi-level predictors, and cognitive correlates of race-, SES- (and/or sex) with preclinical MRI markers of AD/ADRD risk and accelerated brain aging will facilitate appropriate strategies in prevention and intervention for the reduction and ultimate elimination of related health disparities in AD/ADRD.