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Toward reducing disparities: identifying drivers of clinical Alzheimer’s disease in African American populations

Royse, Sarah (2023) Toward reducing disparities: identifying drivers of clinical Alzheimer’s disease in African American populations. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Royse, Sarahsak225@pitt.edusak2250000-0003-4846-0180
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRosano, Caterinarosanoc@edc.pitt.educar23500000-0002-0909-1506
Committee MemberSnitz, Bethsnitbe@upmc.edubes90000-0002-9978-1374
Committee MemberBertolet, Marniemhb12@pitt.edumhb120000-0002-5799-9033
Committee MemberCohen, Anncohenad@upmc.eduanc25970000-0001-7395-9624
Committee MemberHill, Ashleyavh16@pitt.eduavh160000-0002-3535-1404
Committee MemberZmuda, Josephzmudaj@edc.pitt.eduepidjmz0000-0001-7237-3162
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


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