18 Nov 2004

The metabolic syndrome—a constellation of cardiovascular and diabetes risk factors such as abdominal obesity, high blood pressure, and high triglycerides—is associated with an increased risk of cognitive decline, according to a report in the 10 November JAMA. Kristine Yaffe of the University of California, San Francisco, and her colleagues there and at other institutions also provide evidence suggesting that inflammation is an important factor in whether or not metabolic syndrome will cause cognitive decline.

Yaffe and colleagues followed elderly subjects (aged 70-79 years) in a longitudinal, prospective, observational study of aging and body composition. In order to better correlate results with the effects of the metabolic syndrome, the researchers excluded people with diabetes or very high elevations of blood pressure or triglycerides. Of the 2,632 subjects, 1,016 had metabolic syndrome (defined as three or more of the following: abdominal obesity, high blood pressure, high triglycerides, high fasting glucose, or low HDL cholesterol) at baseline. Compared with the remaining 1,616 subjects, those with metabolic syndrome were more likely to experience cognitive impairment over the next four years (26 percent vs. 21 percent, multivariate adjusted relative risk, 1.20; 95 percent CI, 1.02-1.41). Cognitive impairment was defined as a five-point or greater decline on a modified MMSE at follow-up in three or five years.

The researchers report a statistically significant interaction between inflammation (as indicated by increased serum IL6 and C-reactive protein) and metabolic syndrome in increasing the risk of cognitive decline (P = .03). When they stratified subjects into tertiles by their serum levels of these two proinflammatory markers, Yaffe and colleagues found that among subjects who were in the highest tertiles for both markers, the presence of metabolic syndrome was associated with an increased risk of cognitive impairment on follow-up (multivariate adjusted relative risk, 1.66; 95 percent CI, 1.19-2.32). Conversely, among subjects with the lowest tertiles of inflammatory markers, the presence of metabolic syndrome did not increase the likelihood of cognitive decline (multivariate adjusted relative risk, 1.08; 95 percent CI, 0.89-1.30).

How inflammation, metabolic syndrome, and cognitive impairment are related is unclear. For example, does metabolic syndrome lead to inflammation that can, in turn, impact cognition, or does inflammation promote metabolic syndrome? Or, does the cause/effect relationship run both ways? Much remains to be worked out about the interrelationship among metabolic syndrome, inflammation, and cognitive decline, according to the authors.—Hakon Heimer