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.