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Kristine Yaffe, MD; Alka Kanaya, MD; Karla Lindquist, MS; Eleanor M. Simonsick, PhD; Tamara Harris, MD; Ronald I. Shorr, MD; Frances A. Tylavsky, PhD; Anne B. Newman, MD, MPH

JAMA. 2004;292:2237-2242.

Context  Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition.

Objective  To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation.

Design and Setting  A 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sites.

Participants  A total of 2632 black and white elders (mean age, 74 years).

Main Outcome Measures  Association of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years. Cognitive impairment was defined as at least a 5-point decline.

Results  Compared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02-1.41). There was a statistically significant interaction with inflammation and the metabolic syndrome (P = .03) on cognitive impairment. After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 1.66; 95% CI, 1.19-2.32). Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 1.08; 95% CI, 0.89-1.30). Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = .04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = .44).

Conclusion  These findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation.

Author Affiliations: Departments of Psychiatry, Neurology, and Epidemiology (Dr Yaffe), Geriatrics (Ms Lindquist), and Medicine (Dr Kanaya), University of California, San Francisco; Clinical Research Branch, National Institute on Aging, Baltimore, Md (Dr Simonsick); Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Md (Dr Harris); Department of Preventive Medicine, University of Tennessee at Memphis (Drs Shorr and Tylavsky); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pa (Dr Newman).

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