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From the Department of Medicine (Drs. Mosley, Hutchinson, and Grothues), University of Mississippi Medical Center, Jackson, MS; Department of Neurology (Dr. Knopman), Mayo Clinic, Rochester, MN; Department of Biostatistics (Dr. Catellier), University of North Carolina, Chapel Hill, NC; Department of Radiology (Dr. Bryan), Hospital of the University of Pennsylvania, Philadelphia; Division of Epidemiology (Dr. Folsom), School of Public Health, University of Minnesota, Minneapolis; National Heart, Lung, and Blood Institute (Dr. Cooper), Bethesda, MD; Department of Public Health Sciences (Dr. Burke), Wake Forest University School of Medicine, Winston-Salem, NC; Health Evaluation Sciences (Dr. Liao), Penn State University Hershey Medical Center, Hershey; and School of Hygiene and Public Health (Dr. Szklo), The Johns Hopkins Medical Institutions, Baltimore, MD.
Address correspondence and reprint requests to Dr. Thomas H. Mosley, Jr., Department of Medicine (Geriatrics), University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505; e-mail: tmosley{at}medicine.umsmed.edu
Objective: To examine the association between prevalent cerebral abnormalities identified on MRI and cognitive functioning in a predominantly middle-aged, population-based study cohort.
Methods: Cerebral MRI was performed on 1,538 individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC) cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC, and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and sulcal size were graded by trained neuroradiologists on a semiquantitative, 10-point scale. Cognitive functioning was assessed using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT).
Results: High ventricular grade was independently associated with significantly lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., 
10th percentile) on the DWRT. High sulcal grade was associated with a modest decrement in scores on the DWRT. The presence of coexisting high grade WMHs and silent infarcts was independently associated with lower scores on all cognitive tests and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to 6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high-grade abnormalities was associated with increased risk of impaired functioning on all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI 1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple covariates and silent infarcts.
Conclusion: Common changes in brain morphology are associated with diminished cognitive functioning in middle-aged and young-elderly individuals.
Additional material related to this article is available on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the June 28 issue to find the title link for this article.
Supported by contracts NO1-HC-55015, NO1-HC-55016, NO1-HC-55017, NO1-HC-55018, NO1-HC-55019, NO1-HC-55020, NO1-HC-55021, and NO1-HC-55022 from the National Heart, Lung, and Blood Institute, Bethesda, MD. The authors thank the staff and participants in the ARIC study for their contributions.
Presented at the Annual Meeting of the American Academy of Neurology, Philadelphia, May 8, 2001.
Received May 21, 2004. Accepted in final form March 30, 2005.
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