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NEUROLOGY 2005;64:277-281
© 2005 American Academy of Neurology

Midlife cardiovascular risk factors and risk of dementia in late life

R. A. Whitmer, PhD, S. Sidney, MD, J. Selby, MD, S. Claiborne Johnston, MD and K. Yaffe, MD

From Kaiser Permanente Division of Research (Drs. Whitmer, Sidney, and Selby), Oakland, CA; and Departments of Neurology (Drs. Claiborne Johnston and Yaffe), Epidemiology (Drs. Claiborne Johnston and Yaffe), and Psychiatry (Dr. Yaffe), University of California San Francisco.

Address correspondence and reprint requests to Dr. Rachel Whitmer, 2000 Broadway, Kaiser Permanente Division of Research, Oakland, CA 94612; e-mail: raw{at}dor.kaiser.org

Objective: To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort.

Method: The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003.

Results: The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10).

Conclusion: The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.


Supported by grant 1K12AR47659 from the National Institutes of Health.

Received October 19, 2003. Accepted in final form September 8, 2004.




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