Metabolic and Vascular Risk Factor Variability Over 25 Years Relates to Midlife Brain Volume and Cognition

Article type: Research Article

Authors: Shirzadi, Zahra^{a; b; c} | Rabin, Jennifer^{c; d; e; f} | Launer, Lenore J.^g | Bryan, R. Nick^h | Al-Ozairi, Abdullaⁱ | Chhatwal, Jasmeer^j | Al-Ozairi, Ebaaⁱ | Detre, John A.^k | Black, Sandra E.^{b; c; e} | Swardfager, Walter^{c; l; m} | MacIntosh, Bradley J.^{a; b; c; *}

Affiliations: [a] Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada | [b] Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada | [c] Hurvitz Brain Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada | [d] Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, ON, Canada | [e] Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada | [f] Rehabilitation Sciences, University of Toronto, Toronto, ON, Canada | [g] Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA | [h] Department of Diagnostic Medicine, University of Texas, Austin, TX, USA | [i] Dasman Diabetes Institute, Kuwait City, Kuwait | [j] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [k] Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia, PA, USA | [l] Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada | [m] KITE, UHN-Toronto Rehab, Toronto, ON, Canada

Correspondence: [*] Correspondence to: Bradley J. MacIntosh, PhD, Department of Medical Biophysics, University of Toronto, Sunnybrook Research Institute, 2075 Bayview Avenue, M6-180, Toronto, ON, Canada. Tel.: +1 416 480 6100 Ext: 7277; E-mail: [email protected]

Abstract: Background:Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain imaging features. Objective:To investigate whether longitudinal changes in MVRF spanning up to 25 years would be associated with midlife brain volume and cognition. Methods:Participants were from the CARDIA study (N = 467, age at year 25 = 50.6±3.4, female/male = 232/235, black/white = 161/306). Three models were developed, each designed to capture change over time; however, we were primarily interested in the average real variability (ARV) as a means of quantifying MVRF variability across all available assessments. Results:Multivariate partial least squares that used ARV metrics identified two significant latent variables (partial correlations ranged between 0.1 and 0.26, p < 0.01) that related MVRF ARV and regional brain volumes. Both latent variables reflected associations between brain volume and MVRF ARV in obesity, cholesterol, blood pressure, and glucose. Subsequent bivariate correlations revealed associations among MVRF factors, aggregate brain volume and cognition. Conclusion:This study demonstrates that MVRF variability over time is associated with midlife brain volume in regions that are relevant to later-life cognitive decline.

Keywords: Brain volume, cognition, metabolic syndrome, partial least squares, vascular risk factors

DOI: 10.3233/JAD-220340

Journal: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 627-635, 2023