Cerebral small vessel disease burden and racial disparity in vascular cognitive impairment and Alzheimer’s disease and its related dementias

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PROJECT ABSTRACT With an increasing proportion of the population at older ages (i.e., the `graying of America'), there is a growing prevalence of Alzheimer's Disease and Related Dementias (ADRDs). The increase in proportion of older Americans is happening at a faster rate among minority populations compared with non-Hispanic Whites (NHWs), for instance, the number of “oldest” Americans is expected to grow by 81% among non-Hispanic Whites compared to 131% growth among Non-Hispanic Blacks (NHBs) and 328% among Hispanics, by the year 2030. Paralleling this increased racial disparity in the proportion of oldest Americans, is also a racial disparity in the incidence and prevalence of ADRDs. For instance, there is significantly higher prevalence of all dementias among NHBs compared to NHWs, with NHB men and women having a 2 – 2.5 times the prevalence among NHW men or women. Among NHB men, the prevalence of Alzheimer's dementia (AD) is 2.5 times that among NHW men. When only vascular cognitive impairment and dementia (VCID) is examined, NHBs were more than twice as likely to develop VCID even after adjusting for differences in cumulative incidence of stroke, stroke severity and known vascular and dementia risk factors. Suggesting the need to identify other factors that could be contributing to the observed racial or black-white disparity. Our overall goals are to (1) determine whether there is a black-white disparity in the prevalence of magnetic resonance imaging (MRI) defined markers of CSVD among participants in the REGARDS cohort with confirmed stroke/TIA and (2) identify the contributions of CSVD and ADRD genetic and vascular risk factors to the black-white disparity in VCIDs) and ADRDs. We hypothesize that among REGARDS participants who had a stroke or TIA, the black-white disparity in the prevalence and trajectory of VCI and ADRDs is partly due to black-white disparity in the prevalence and burden of CSVD, which could be related to differences in the distribution of vascular and ADRD genetic risk factors. CSVDs are MRI detected brain lesions whose components are cerebral microbleeds (CMBs), white matter hyperintensity (WMH) lesions, lacunes and enlarged perivascular spaces (ePVS) and are associated with vascular risk factors as well as incidence and prevalence of cognitive impairment and dementia. Our hypothesis will be tested based on the following aims: (1) Determine the prevalence, pattern and racial/geographic difference in CSVD and variation in brain volumetric parameters. (2) Examine the association between vascular and genetic (APOE ε4, ABCA7 and TREM2) risk factors, and prevalence or disparity in CSVD and brain volumes. (3) Determine the association between CSVD, brain volumetric measures and incidence, prevalence and trajectory as well as any observed black-white disparity in risk of cognitive impairment and dementia. Completing the above aims will enable us to identify a high-risk population for more targeted VCID prevention or treatment strategies to potentially reduce black-white disparity in VCID. Additionally, the MRI scans retrieved, and the phenotype derived will be a useful resource for further research in REGARDS.