HAI Book 2025 - Flipbook - Page 509
Reese, Alexandria
Intersections of sex and neighborhood disadvantage on Alzheimer9s disease
pathology
Alexandria Reese1,2, Sarah Royse2,3, Beth Snitz3,4, Nirupama Natarajan5,6, James Hengenius7,
Theodore Huppert8, Rebecca Roush6, Geraldine Cisneros6, Alexandra Gogola2, Brian
Lopresti2, Oscar Lopez3,4,6, James Becker3,6, Ann Cohen3,6, C. Elizabeth Shaaban1,3
1
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, US
Department of Radiology, University of Pittsburgh, Pittsburgh, PA, US
3
Alzheimer’s Disease Research Center, University of Pittsburgh, Pittsburgh, PA, US
4
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, US
5
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, US
6
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, US
7
CHU Sainte-Justine Research Centre, Université de Montréal, Montréal, QC, CA
8
Department of Electrical and Computer Engineering, University of Pittsburgh, Pittsburgh, PA, US
2
Background: Differences in Alzheimer9s disease (AD) biomarkers have been reported by sex, but their intersection
with neighborhood disadvantage is not understood.
Methods: Participants were enrolled in the Connectomics in Brain Aging study. Neighborhood disadvantage was
assessed using the area deprivation index (ADI) national rank, where higher scores indicate greater disadvantage.
´-amyloid (A) was measured via global 11C-PiB SUVR. Our vascular (V) measure was lobar unhealthy white matter
connectivity (UWMC), a novel measure indicating the proportion of white matter (WM) connections affected by
WM hyperintensities. Neurodegeneration (N) was measured via cortical thickness from an AD-specific metaregion. Intersectional effects of sex and ADI on AV(N) were examined on the multiplicative and additive scale via
robust and log-binomial regressions, respectively.
Results: The sample included N=182 participants (age 62 years; female sex 66%; Black racialization 49%;
education 14 years; APOE4+ 31%; cognitively impaired 27%; Table 1). In robust regressions, female participants
had greater frontal UWMC (´=0.06, SE=0.02, p=0.0005) and lower occipital UWMC (´=-0.05, SE=0.02, p=0.02)
versus male participants, and high ADI participants had greater frontal (´=0.04, SE=0.02, p=0.04) and temporal
UWMC (´=0.04, SE=0.02, p=0.01) versus low ADI participants (Table 2). Intersectional effects were found such that
female participants with high ADI had the greatest temporal UWMC on the additive (relative excess risk due to
interaction=0.72, 95% CI=[0.11,1.32]) and multiplicative (p-interaction=0.04) scales. Sex-stratified regressions
indicated that high ADI was associated with greater temporal UWMC in female participants (´=0.07, SE=0.02,
p=0.001), but not male participants (´=-0.002, SE=0.03, p=0.96; Figure 1). Results of sensitivity analyses with
temporal WMH instead of UWMC were similar.
Conclusion: We confirmed differences in AV(N) by sex and ADI. Intersectional effects were found on temporal
UWMC, such that women with high ADI had the greatest burden. Understanding the role of neighborhood
disadvantage on V is important for future interventions, especially for women.
HAI2025 - 509
