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From the Center for Health Sciences (Drs. Swan and Carmelli, and L.M. Jack), SRI International, Menlo Park, CA; the Department of Neurology (Dr. DeCarli), University of Kansas, Kansas City, KS; the Department of Neurology (Dr. Miller), Harbor-UCLA, Torrance, CA; the Department of Medical and Molecular Genetics (Dr. Reed), Indiana University School of Medicine, Indianapolis, IN; and the Department of Neurology (Dr. Wolf), Boston University, Boston, MA.
Address correspondence and reprint requests to Dr. Gary E. Swan, Center for Health Sciences, SRI International (formerly Stanford Research Institute), 333 Ravenswood Avenue, Menlo Park, CA 94025.
Objective: To investigate the association between midlife systolic blood pressure (SBP) and late-life cognitive decline and brain morphology in a sample of community-dwelling elderly men 68 to 79 years of age.
Methods: Subjects are surviving members from the prospective National Heart, Lung, and Blood Institute Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995 through 1997, underwent brain MRI and repeated assessment of neurobehavioral functioning. Quantification of the MR images determined cerebral volume and total volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP levels measured in 1970, 1980, and 1985 were used to classify subjects into low, medium, and high midlife SBP categories. A 10-year change in performance on the Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual Retention Test, and Verbal Fluency Test was also calculated for these subjects. For all reported analyses, patients were treated as genetically unrelated individuals.
Results: Subjects with high midlife SBP experienced a greater decline in cognitive performance and had larger WMHI volumes at follow-up in late life than did those with low midlife SBP. Decreased brain parenchyma and increased WMHI volumes were associated with decline in neurobehavioral functioning as measured in late life independent of age, education, and baseline levels of cognition.
Conclusions: Midlife SBP is a significant predictor of both decline in cognitive function and MR volumetric measures of brain atrophy in late life. Because decline in neurobehavioral functioning was associated with decreased brain volume and increased WMHI volume, we conclude that the long-term impact of elevated SBP on decline in late-life neurobehavioral functioning is likely to be mediated through its chronic, negative effect on structural characteristics of the brain.
Supported by grant HL51429 from the National Heart, Lung, and Blood Institute, Washington, DC.
Presented in part at the 49th annual meeting of the American Academy of Neurology; Boston, MA; April 1997.
Received March 4, 1998. Accepted in final form June 23, 1998.
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