Association of Cardiovascular Risk Factors with Cerebral Perfusion in Whites and African Americans

Article type: Research Article

Authors: Clark, Lindsay R.^{a; b; c; *} | Zuelsdorff, Megan^{a; d} | Norton, Derek^e | Johnson, Sterling C.^{a; b; c} | Wyman, Mary F.^{c; f} | Hancock, Laura M.^g | Carlsson, Cynthia M.^{a; b; c} | Asthana, Sanjay^{a; c} | Flowers-Benton, Susan^h | Gleason, Carey E.^{a; c; 1} | Johnson, Heather M.^{i; 1}

Affiliations: [a] Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [b] Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [c] Geriatric Research Education and Clinical Center, William S Middleton Memorial Veterans Hospital, Madison, WI, USA | [d] University of Wisconsin School of Nursing, Madison, WI, USA | [e] Department of Biostatistics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [f] Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [g] Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [h] Department of Family Medicine and Community Health, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [i] Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Correspondence: [*] Correspondence to: Lindsay R. Clark, PhD, Assistant Professor and Licensed Neuropsychologist, 600 Highland Avenue, J5/1 Mezzanine, Madison, WI 53792, USA. Tel.: +1 608 263 4405; Fax: +1 608 265 3091; E-mail: lrclark@medicine.wisc.edu.

Note: [1] Co-senior authors.

Abstract: Background:Midlife cardiovascular risk factors increase risk for Alzheimer’s disease (AD). Despite disproportionately high cardiovascular disease and dementia rates, African Americans are under-represented in studies of AD risk and research-based guidance on targeting vascular risk factors is lacking. Objective:This study investigated relationships between specific cardiovascular risk factors and cerebral perfusion in White and African American adults enriched for AD risk. Methods:Participants included 397 cognitively unimpaired White (n = 330) and African American (n = 67) adults enrolled in the Wisconsin Alzheimer’s Disease Research Center who underwent pseudo-continuous arterial spin labeling MRI. Multiple linear regression models examined independent relationships between cardiovascular risk factors and mean cerebral perfusion. Subsequent interaction and stratified models assessed the role for APOE genotype and race. Results:When risk factor p-values were FDR-adjusted, diastolic blood pressure was significantly associated with mean perfusion. Tobacco use, triglycerides, waist-to-hip ratio, and a composite risk score were not associated with perfusion. Without FDR adjustment, a relationship was also observed between perfusion and obesity, cholesterol, and fasting glucose. Neither APOE genotype nor race moderated relationships between risk factors and perfusion. Conclusion:Higher diastolic blood pressure predicted lower perfusion more strongly than other cardiovascular risk factors. This relationship did not vary by racial group or genetic risk for AD, although the African American sample had greater vascular risk burden and lower perfusion rates. Our findings highlight the need to prioritize inclusion of underrepresented groups in neuroimaging studies and to continue exploring the link between modifiable risk factors, cerebrovascular health, and AD risk in underrepresented populations.

Keywords: Aging, Alzheimer’s disease, blood pressure, cerebrovascular circulation, neuroimaging, obesity

DOI: 10.3233/JAD-190360

Journal: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 649-660, 2020