BACKGROUND: Microglia-driven inflammation is a common pathological process associated with cognitive decline in aging. However, most clinicopathologic evidence of association of microglia to cognitive decline has been derived predominantly from older White adults and this association in older Black adults remains poorly understood. This study examined the racial differences in the level of microglia and the association between microglia and cognitive decline in older Black adults and evaluated whether their relationship differs by race.

METHODS: We conducted a nested substudy including 153 Black decedents and 293 White decedents from autopsied participants who were enrolled in 1 of 4 longitudinal cohort studies of Rush Alzheimer’s Disease Center. Participants had a complete neuropathologic evaluation, including microglia assessment, Alzheimer’s disease, and other neurodegenerative and cerebrovascular pathologies. Total microglia density was quantified in the hippocampal CA1/subiculum region using machine learning-based classifiers trained on digitized CR3-43-stained images via the HALO digital pathology platform. Linear regression analyses employed to assess racial differences in microglia density. We then used mixed-effects models to examine the association between microglial density and cognitive decline among Black decedents. Secondary analyses evaluated racial differences in these associations.

RESULTS: Participants had a mean age of 85 years at death with 67% being women. Black decedents had significantly greater microglial density compared with White decedents. Higher microglial density in Black decedents was associated with a faster rate of decline in global cognition and in three cognitive domains: episodic memory, semantic memory, and perceptual speed. Secondary analyses indicated that the associations between microglial density and decline in global cognition and cognitive domains were similar across racial groups.

CONCLUSIONS: These findings highlight potential racial disparities in brain inflammation and suggest that microglia-related inflammatory processes could be important pathological feature in assessing health disparities among Blacks and Whites.