Royse, Sarah
(2023)
Toward reducing disparities: identifying drivers of clinical Alzheimer’s disease in African American populations.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
African American (AA) populations are disproportionately burdened by clinical Alzheimer’s disease (AD), but do not show more evidence of pathological AD than those who are non-Hispanic white (nHW), suggesting that current pathological disease models are insufficient to explain this disparity. I used a population neuroscience approach to interrogate three potential drivers of clinical AD disparities, where each driver represented group of clinical AD risk factors: white matter hyperintensities (WMH; neuropathological risk), apolipoprotein-E genotype (APOE; genetic risk), and perceived discrimination (social/contextual risk). In the first study, I used a novel method to quantify WMH, unhealthy white matter connectivity (UWMC), and examined overall and racialized group differences in the association of UWMC in AD pathology-affected brain regions with cognition. Compared to nHW participants, those who were AA exhibited more UWMC, worse cognitive function, and similar UWMC-and-cognitive function relationships, indicating that racialized group disparities in clinical AD may be driven partially by differential burden of WMH/UWMC. The second study examined overall and racialized group differences in relationships of APOE*4 and APOE*2 with in vivo Aβ and tau. Relative to those who were nHW, AA participants were more likely to carry at least one APOE*4 or APOE*2 allele, exhibited less Aβ, and showed a weaker (non-significant) relationship between APOE*4 and Aβ; all other relationships were non-significant. Thus, APOE*4 may not drive racialized group disparities in clinical AD through risk of pathological AD; the role of APOE*2 deserves further study. Finally, I tested overall and racialized group differences in associations of mid-life perceived discrimination with late-life AD pathology and cognition. AA participants exhibited more mid-life perceived discrimination, worse late-life executive function, and a stronger relationship between mid-life perceived discrimination and late-life executive function than nHW participants; no other associations were significant. Clinical AD disparities may therefore be partially driven by differential burden and consequences of mid-life perceived discrimination in AA populations. Overall, I found that UWMC in AD pathology-affected regions may contribute to clinical AD disparities. Interactions between UWMC and AD pathology on clinical AD and whether APOE*4 and perceived discrimination and other social/contextual exposure influence UWMC through conferring vascular risks should be studied further.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
24 August 2023 |
| Date Type: |
Publication |
| Defense Date: |
20 June 2023 |
| Approval Date: |
24 August 2023 |
| Submission Date: |
20 July 2023 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
158 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Alzheimer's disease; neuroimaging; racialization |
| Date Deposited: |
24 Aug 2023 13:30 |
| Last Modified: |
24 Aug 2023 13:30 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/45115 |
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