Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults
The Framingham Offspring Study
- Zaldy S. Tan, MD, MPH1,2,3,4⇓,
- Alexa S. Beiser, PHD4,5,6,
- Caroline S. Fox, MD, MPH3,4,7,
- Rhoda Au, PHD4,5,
- Jayandra J. Himali, MS4,6,
- Stephanie Debette, MD5,
- Charles DeCarli, MD8,
- Ramachandran S. Vasan, MD4,9,
- Philip A. Wolf, MD4,5 and
- Sudha Seshadri, MD4,5
- 1Geriatric Research Education and Clinical Center, Veterans Administration Boston Healthcare System, Boston, Massachusetts
- 2Department of Medicine, Division of Aging, Brigham and Women’s Hospital, Boston, Massachusetts
- 3Harvard Medical School, Boston, Massachusetts
- 4National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts
- 5Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
- 6Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- 7Department of Medicine, Division of Endocrinology, Hypertension and Metabolism, Brigham and Women’s Hospital, Boston, Massachusetts
- 8Department of Neurology, University of California–Davis, Davis, California
- 9Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
- Corresponding author: Zaldy S. Tan, .
OBJECTIVE Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults.
RESEARCH DESIGN AND METHODS Framingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998–2001) constituted our study sample (n = 2,439; 1,311 women; age 61 ± 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-ε4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C).
RESULTS We observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P < 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P < 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P < 0.007).
CONCLUSIONS Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-0308/-/DC1.
- Received February 14, 2011.
- Accepted May 16, 2011.
- © 2011 by the American Diabetes Association.
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