4 Interactions of Inflammation and Psychosocial Stress on White Matter Integrity Over Time in Older Black Adults

Abstract

Objective:Higher levels of inflammation are associated with risk factors for Alzheimer’s disease and related dementias (ADRD) in older Black adults including psychosocial stressors (e.g., discrimination and early life adversity) and white matter alterations. Yet, limited work has investigated these risk factors together in a longitudinal neuroimaging study, despite the well-known ADRD disparity in older Black adults. Using data from the Minority Aging Research Study and African American Clinical Core of the Rush Alzheimer’s Disease Center, we examined interactions of psychosocial stressors and change in inflammation on changes in white matter integrity as measured via diffusion tensor imaging (DTI).Participants and Methods:Older Black adults (n=102) without known dementia at baseline (age=75.8±6.1 years; 87.3% female; education=15.4±2.7 years) completed blood draws at two time points (follow-up=2.4±0.7 years), neuroimaging at two or more time points (follow-up=3.7±1.8 years), and psychosocial questionnaires at one time point coinciding with the first blood draw/neuroimaging. Blood serum was assayed using highly-sensitive multiplexed sandwich ELISA for interleukin-6, c-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-a) and a change score was calculated for each inflammatory marker (T2 - T1). The Williams Everyday Discrimination Scale quantified experiences of discrimination in all participants and a 16-item questionnaire of emotional and physical trauma from age 0-18 assessed early life adversity in a participant subset (n=63). DTI-derived tract-based spatial statistics (TBSS) slope change measures for trace of the diffusion tensor, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were calculated, with the first two scans matched in time to blood assays. Linear regression models investigated interactions of each inflammatory marker change score (separately) and either discrimination or early life adversity (separately) on trace, FA, AD, and RD slopes as individual outcomes adjusting for age, sex, education, white matter hyperintensities (total volume and voxelwise), cardiovascular risk factors, statin and analgesic medications, thyroid conditions, and depression. Statistical significance was determined at p<0.05 using family wise error correction and threshold free cluster enhancement.Results:Discrimination moderated the relationship between TNF-a and AD whereby those with increasing TNF-a and higher levels of discrimination had increasing levels of AD over time in white matter tracts connecting the left and right cerebellum, the left pallidum and medulla, and the left superior frontal gyrus and left thalamus. Both discrimination and early life adversity moderated associations between CRP and AD, where increases in CRP and higher psychosocial stressors (of either type) resulted in decreasing AD over time in tracts involving cingulate, frontal, and parietal regions. Discrimination and early life adversity also moderated associations between CRP and RD, where increasing CRP combined with greater psychosocial stressors resulted in decreasing RD in right hemisphere association and projection tracts connecting frontal, parietal, central, and subcortical regions.Conclusions:TNF-a and CRP interacted with measures of psychosocial stress to associate with DTI-derived TBSS slope change measures of AD and RD in differential, and at times, paradoxical ways. Findings suggest that both risk and resilience as related to brain connectivity may be co-occurring in the presence of psychosocial stressors for older Black adults.