Impact of Inflammation and Psychosocial Stress on White Matter and Cognition in Older African Americans

Inflammation has been implicated in the pathogenic process of Alzheimer’s disease and related dementias (ADRD) including detrimental changes to white matter integrity and cognition. Inflammation has also been associated with psychosocial stressors in older African Americans. Few studies have investigated inflammation, psychosocial stressors, and brain-behavior longitudinally within this population despite increased risk for ADRD. We examined associations between changes in inflammation and changes in cognition and white matter integrity over time, and whether psychosocial stressors modify these relationships in older African Americans. 114 participants without dementia at baseline (mean age=75.69 years; 85.1% female) completed blood draws, cognitive testing, questionnaires of discrimination and early life adversity, and MRI at two or more time points (mean follow-up: cognitive=5.42 years; MRI=3.72 years). Blood serum from two time points was assayed using ELISA for interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) and a change score was created for each inflammatory marker. Raw scores from 19 neuropsychological tests were z-scored and combined to create a global cognition composite and five cognitive domain scores. Neuroimaging metrics including white matter hyperintensities; diffusion tensor imaging indices of fractional anisotropy, trace, radial diffusivity (RD), and axial diffusivity (AD); and R2 quantified white matter integrity. In linear mixed models adjusted for relevant covariates, there were no significant associations between any inflammatory change scores and cognition or white matter integrity indices longitudinally. Discrimination was associated with change in IL-6 over time, and significantly modified the association between CRP and cognitive change where participants with increasing CRP and higher levels of discrimination demonstrated steeper declines in perceptual speed. Discrimination significantly modified associations between TNF-α and AD where higher discrimination and increasing TNF-α resulted in increases in AD over time. Higher levels of discrimination and early life adversity coupled with increasing CRP resulted in RD and AD decreases over time, as well. Together, findings indicate that considering the combined effect of inflammation and psychosocial stressors on white matter integrity and cognition in longitudinal studies of older African Americans may be an important combination for identifying risk and resilience factors in a population with increased risk for ADRD.