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Neurology 2002;59:371-378
© 2002 American Academy of Neurology

Interleukin-6 and risk of cognitive decline

MacArthur Studies of Successful Aging

J. D. Weaver, MD, M.-H. Huang, DrPH, M. Albert, PhD, T. Harris, MD, MS, J. W. Rowe, MD and T. E. Seeman, PhD

From the Division of Geriatrics (Drs. Weaver, Huang, and Seeman), UCLA School of Medicine, Los Angeles, CA; Department of Psychiatry/Gerontology (Dr. Albert), Massachusetts General Hospital, Harvard Medical School, Boston; Office of Geriatric Epidemiology (Dr. Harris), National Institute on Aging, Bethesda, MD; and Mount Sinai Medical School (Dr. Rowe), New York, NY.

Address correspondence and reprint requests to Dr. Teresa E. Seeman, Division of Geriatrics, UCLA School of Medicine, 10945 Le Conte Ave., Suite 2339, Los Angeles, CA 90095-1687; e-mail: tseeman{at}mednet.ucla.edu

Objective: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people.

Methods: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up).

Results: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders.

Conclusions: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.




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