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Kristine Yaffe, MD; Andrea L. Weston, MPH; Terri Blackwell, MA; Kathryn A. Krueger, MD

Arch Neurol. 2009;66(3):324-328.

Background  Several studies support a role for cardiovascular risk factors in cognitive aging. The metabolic syndrome, a constellation of cardiovascular risk factors, is common in elderly people. A growing but conflicting body of literature suggests that the metabolic syndrome may be associated with cognitive impairment.

Objective  To investigate the association between the metabolic syndrome and its components and incident cognitive impairment in older women.

Design  We prospectively determined if the metabolic syndrome and its components were associated with a 4-year risk of developing cognitive impairment (dementia, mild cognitive impairment, or low global cognitive test score).

Setting  The study was conducted at 180 clinical centers in 25 countries.

Participants  A total of 4895 older women (mean age, 66.2 years) with osteoporosis who were part of an ancillary study to determine clinically relevant cognitive impairment were included in this study. These women were free of baseline cognitive impairment and had metabolic syndrome component measures.

Main Outcome Measures  Clinically significant cognitive impairment was defined to include women with clinically adjudicated dementia or MCI and women who had a Short Blessed test score greater than 6 (consistent with impairment), but whose cases were not clinically adjudicated. Logistic regression analysis was used to examine the association between presence of the metabolic syndrome and development of clinically significant cognitive impairment.

Results  A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41). The mean (SD) number of metabolic syndrome components for all women was 1.0 (1.1); 518 women (10.6%) were obese, 895 (18.3%) had hypertriglyceridemia, 1200 (24.5%) had low high-density lipoprotein cholesterol levels, 1944 (39.7%) had high blood pressure, and 381 (7.8%) had high fasting blood glucose levels. There was a 23.0% age-adjusted increase in the risk of developing cognitive impairment (odds ratio, 1.23; 95% confidence interval, 1.09-1.39) per unit increase in the number of components. Further multivariable adjustment somewhat reduced the effect.

Conclusion  We found an association between the metabolic syndrome and the number of components and risk of developing cognitive impairment in older women. Additional studies are needed to determine if screening and close management of these at-risk elderly women would diminish the incidence of cognitive impairment.

Author Affiliations: Departments of Psychiatry (Dr Yaffe and Ms Weston), Neurology (Dr Yaffe), and Epidemiology and Biostatistics (Dr Yaffe), University of California, San Francisco, and the San Francisco Veterans' Affairs Medical Center (Dr Yaffe and Ms Weston); California Pacific Medical Center Research Institute, San Francisco (Ms Blackwell); and Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana (Dr Krueger).

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