OBJECTIVES: To investigate the effect of metabolic syndrome on cognitive function in an elderly Latino population and to determine whether inflammation modifies this association. DESIGN: A longitudinal cohort study. SETTING: Sacramento area and the surrounding California counties from 1998 to 1999. PARTICIPANTS: One thousand six hundred twenty-four Latinos aged 60 and older who participated in the Sacramento Area Latino Study of Aging. MEASUREMENTS: Baseline metabolic syndrome was calculated using the Third Adult Treatment Panel of the National Cholesterol Education Program. Cognitive function was measured using the Modified Mini-Mental State Examination (3MS) and the Delayed Word-List Recall (DelRec), a verbal memory test. The effect of metabolic syndrome on cognitive change scores was examined using random effects models; in addition, the effect of the individual components of the syndrome on cognitive change was examined. RESULTS: Of the 1,624 participants, 718 (44%) had metabolic syndrome at baseline. Those with metabolic syndrome had worse 3-year change scores on 3MS (P=.04) and DelRec (P=.03). Multivariate adjustment attenuated the results for DelRec but not for 3MS. This association was especially pronounced in participants with a high serum level of inflammation, resulting in an average 3MS score 0.64 points lower per year (P=.03) for those with metabolic syndrome. Individual components of metabolic syndrome were not associated with cognitive decline except for elevated glucose on the DelRec (P=.02) and high blood pressure on 3MS (P=.05). CONCLUSION: Metabolic syndrome and inflammation may both contribute to cognitive decline in older people of diverse backgrounds. The results also suggest that, in elderly Latinos, the composite measure of metabolic syndrome is a greater risk for cognitive decline than its individual components.