Association of Cardiovascular and Alzheimer’s Disease Risk Factors with Intracranial Arterial Blood Flow in Whites and African Americans

Article type: Research Article

Authors: Clark, Lindsay R.^{a; b; c} | Norton, Derek^d | Berman, Sara E.^e | Johnson, Sterling C.^{a; b; c} | Bendlin, Barbara B.^{a; b} | Wieben, Oliver^{f; g} | Turski, Patrick^{f; g} | Carlsson, Cynthia^{a; b; c} | Asthana, Sanjay^{a; c} | Gleason, Carey E.^{a; c; 1} | Johnson, Heather M.^{h; 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] Department of Biostatistics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [e] Medical Scientist and Neuroscience Training Programs, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [f] Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [g] Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [h] Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Correspondence: [*] Correspondence to: Heather M. Johnson, MD, MS, MMM, FAHA, FACC, Associate Professor of Medicine, Associate Chief of Cardiology for Faculty Affairs, University of Wisconsin School of Medicine & Public Health, H4/512 CSC, MC 3248; 600 Highland Avenue, Madison, WI 53792, USA. Tel.: +1 608 262 2075; Fax: +1 608 263 0405; E-mail: [email protected].

Note: [1] Co-senior authors.

Abstract: Background:Alzheimer’s disease (AD) has a higher prevalence among African Americans. Targeting cardiovascular and metabolic risk factors may be potential mechanisms to modify AD risk and address racial/ethnic disparities in AD dementia. Objective:This study investigated relationships among cardiovascular and metabolic risk factors, APOE genotype, AD biomarkers, and intracranial arterial blood flow in Whites and African Americans enriched for AD risk. Methods:399 cognitively unimpaired adults from the Wisconsin Alzheimer’s Disease Research Center completed physical and neuroimaging examinations. A 4D Flow MRI sequence (phase-contrast vastly under sampled isotropic projection imaging) measured intracranial arterial flow in the Circle of Willis. Linear mixed-effects regression models estimated relationships between risk factors and intracranial arterial flow and tested interactions with racial group, APOE genotype, and AD biomarkers, with separate models per risk factor. Results:Higher fasting glucose was associated with lower intracranial arterial flow; no additional relationships between flow and risk factors were observed. Main effects of racial group were observed, without an interaction, indicating lower flow in African Americans compared to Whites. In race-stratified analyses, higher glucose and triglycerides were associated with lower flow for African Americans, but not for Whites. No main effects or interactions among risk factors, APOE, or AD biomarkers, and flow were observed. Conclusion:Elevated fasting glucose and triglycerides were associated with lower intracranial arterial flow; these relationships were more prominent in African Americans. Targeting metabolic risk factors may impact intracranial arterial health. Additional research is needed to determine if this will impact disparities in dementia prevalence.

Keywords: African Americans, aging, Alzheimer’s disease, Apolipoprotein E4, cerebrovascular circulation, glucose, metabolic syndrome, neuroimaging, risk factors

DOI: 10.3233/JAD-190645

Journal: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 919-929, 2019