Hypertensive Aspects of Cardiometabolic Disorders Are Associated with Lower Brain Microstructure, Perfusion, and Cognition

Article type: Research Article

Authors: Hughes, Timothy M.^{a; 1} | Lockhart, Samuel N.^{a; 1; *} | Suerken, Cynthia K.^b | Jung, Youngkyoo^c | Whitlow, Christopher T.^d | Bateman, James R.^e | Williams, Benjamin J.^e | Espeland, Mark A.^{a; b} | Sachs, Bonnie C.^{a; e} | Williamson, Jeff^a | Cleveland, Maryjo^a | Yang, Mia^a | Rogers, Samantha^a | Hayden, Kathleen M.^f | Baker, Laura D.^a | Craft, Suzanne^a

Affiliations: [a] Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA | [b] Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA | [c] Department of Radiology, School of Medicine, University of California, Davis, CA, USA | [d] Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA | [e] Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC, USA | [f] Department of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence: [*] Correspondence to: Samuel N. Lockhart, PhD, Wake Forest School of Medicine, Medical Center Blvd. Winston-Salem, NC 27157, USA. Tel.: +1 336 716 8145; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Cardiometabolic disorders (hypertension, diabetes) are key modifiable risk factors for Alzheimer’s disease and related disorders. They often co-occur; yet, the extent to which they independently affect brain structure and function is unclear. Objective:We hypothesized their combined effect is greater in associations with cognitive function and neuroimaging biomarkers of white matter (WM) health and cerebral perfusion in a diverse older adult cohort. Methods:Participants aged 50-85 years received: clinical evaluation, oral glucose tolerance testing, neuroimaging, cognitive testing, and adjudication. Neuroimaging included: T1 (gray [GM]/WM segmentation, regional volumes/thicknesses); FLAIR (WM hyperintensity volume [WMHv]; arterial spin labeling (cerebral blood flow); diffusion tensor imaging (fractional anisotropy [FA]); and neurite orientation dispersion and density imaging (Free Water). Hypertension (HTN) and impaired glucose tolerance (IGT) were staged and cardiometabolic status was categorized (HTN only, IGT only, IGT+HTN, neither). Multivariable linear regression modeled associations with cognitive and neuroimaging measures (covariates: age, gender, race). Results:MRI was available for 478 participants (35% mild cognitive impairment, 10% dementia) with mean age 70±8 years, 74% with HTN, 61% with IGT, and 15% self-identified as Black/African-American. IGT+HTN was significantly associated with cognitive impairment, higher WM Free Water and WMHv, lower FA, and lower GM perfusion compared to neither factor. HTN alone was associated with poorer cognition and lower GM perfusion. Cardiometabolic factors were not associated with GM macrostructure (volumes, temporal lobe cortical thickness) or cognitive status. Conclusion:HTN and its co-occurrence with IGT (HTN+IGT) were associated with lower global cognitive performance and reduced GM perfusion and impaired WM microstructure.

Keywords: Brain, cognition, hyperglycemia, hypertension

DOI: 10.3233/JAD-220646

Journal: Journal of Alzheimer's Disease, vol. 90, no. 4, pp. 1589-1599, 2022