Association of neighborhood-level disadvantage with neurofibrillary tangles.

Abstract

Neighborhood disadvantage, a social exposome measure reflecting income, education, employment, and housing in a census-block group, is associated with markers of Alzheimer's disease brain health such as brain volume and amyloid plaque presence. Yet it is not known whether this association extends to neurofibrillary degeneration, signaling a stronger link to neuropathology confirmed Alzheimer's disease. A cross sectional analysis was conducted using a sample of decedents from two Alzheimer's Disease Research Center brain banks with known Braak stage and neighborhood disadvantage ranking from 1990-2016 (n=428). Neurofibrillary tangle Braak stage was abstracted from data collected via the Neuropathology Data Set form or autopsy reports for earlier donations. The main exposure was neighborhood-level disadvantage measured by the Area Deprivation Index. Generalized ordered logistic regression with site-level clustered standards errors was used to model the ordinal neurofibrillary B score adjusting for age, sex, rurality, geographic proximity to the Alzheimer center, and year of death. Living in a disadvantaged neighborhood at the time of death was associated with more severe neurofibrillary degeneration: for every decile increase in neighborhood disadvantage, there was a 2% increase in the odds of having a more severe B score (OR=1.02, 95% CI, 1.01-1.03) after adjustment. This 2% increase was proportional when comparing the odds at each increasing level of the neurofibrillary tangle B score-when comparing the odds of B score (1,2,3,) vs (0), B score (2,3) vs (0,1), and B score (3) vs (0,1,2). With these new findings, neighborhood disadvantage has been associated with both of the hallmarks signs of Alzheimer's disease neuropathology. Given that Alzheimer's is a life course problem with neuropathologic changes accumulating over decades, future work should apply a life course approach to understand how lifetime exposure accumulation impacts brain health. Taking such a perspective can move the field closer to uncovering and disrupting the social-to-biological pathways impacting Alzheimer's disease brain health and related disparities.