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Divergent Influences of Cardiovascular Disease Risk Factor Domains on Cognition and Gray and White Matter Morphology

Gonzales, Mitzi M. PhD; Ajilore, Olusola MD, PhD; Charlton, Rebecca C. PhD; Cohen, Jamie BA; Yang, Shaolin PhD; Sieg, Erica PsyD; Bhaumik, Dulal K. PhD; Kumar, Anand MD; Lamar, Melissa PhD

doi: 10.1097/PSY.0000000000000448

Objective Hypertension, diabetes, dyslipidemia, and obesity are associated with preclinical alterations in cognition and brain structure; however, this often comes from studies of comprehensive risk scores or single isolated factors. We examined associations of empirically derived cardiovascular disease risk factor domains with cognition and brain structure.

Methods A total of 124 adults (age, 59.8 [13.1] years; 41% African American; 50% women) underwent neuropsychological and cardiovascular assessments and structural magnetic resonance imaging. Principal component analysis of nine cardiovascular disease risk factors resulted in a four-component solution representing 1, cholesterol; 2, glucose dysregulation; 3, metabolic dysregulation; and 4, blood pressure. Separate linear regression models for learning, memory, executive functioning, and attention/information processing were performed, with all components entered at once, adjusting for age, sex, and education. MRI analyses included whole-brain cortical thickness and tract-based fractional anisotropy adjusted for age and sex.

Results Higher blood pressure was associated with poorer learning (B = −0.19; p = .019), memory (B = −0.22; p = .005), and executive functioning performance (B = −0.14; p = .031), and lower cortical thickness within the right lateral occipital lobe. Elevated glucose dysregulation was associated with poorer attention/information processing performance (B = −0.21; p = .006) and lower fractional anisotropy in the right inferior and bilateral superior longitudinal fasciculi. Cholesterol was associated with higher cortical thickness within left caudal middle frontal cortex. Metabolic dysfunction was positively associated with right superior parietal lobe, left inferior parietal lobe, and left precuneus cortical thickness.

Conclusions Cardiovascular domains were associated with distinct cognitive, gray, and white matter alterations and distinct age groups. Future longitudinal studies may assist in identifying vulnerability profiles that may be most important for individuals with multiple cardiovascular disease risk factors.

From the Departments of Psychiatry (Gonzales, Ajilore, Cohen, Yang, Bhaumik, Kumar, Lamar), Bioengineering (Yang), and Radiology (Yang), and Biostatistical Research Center (Bhaumik), University of Illinois at Chicago, Chicago, Illinois; Department of Mental Health (Gonzales), VA Northern California Healthcare System, Martinez, California; Department of Psychology (Charlton), Goldsmiths University of London, London, England, UK; and Department of Clinical Psychology (Sieg), The Chicago School of Professional Psychology, Chicago, Illinois.

Supplemental Content

Address correspondence and reprint requests to Melissa Lamar, PhD, Rush Alzheimer's Disease Center, 600 South Paulina St, Room 1029, Chicago, IL 60612. E-mail:

Received for publication November 29, 2015; revision received December 19, 2016.

Copyright © 2017 by American Psychosomatic Society
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