OBJECTIVE - Recent evidence suggests that the metabolic syndrome and inflammation affect cognitive decline in old age and that they reinforce each other. However, it is not known what the roles of the individual components of the metabolic syndrome on cognition are. RESEARCH DESIGN AND METHODS - The sample consisted of 1,183 participants in the Longitudinal Aging Study Amsterdam who were aged 65-88 years. Metabolic syndrome (U.S. National Cholesterol Education Program definition) and its individual components and the inflammatory markers C-reactive protein (CRP) and α1-antichymotrypsin (ACT) were assessed. Cognitive assessments included general cognition (Mini-Mental State Examination), memory (verbal learning test), fluid intelligence (Raven's Matrices), and information processing speed (coding task). RESULTS - Of the sample, 36.3% had metabolic syndrome. Metabolic syndrome was significantly associated with all cognitive measures (P < 0.05). Of the individual components, hyperglycemia was most strongly and significantly associated with cognitive function (multivariate adjusted models; B values, indicating differences in scores between both groups, ranging from -0.38 to -1.21). There was a significant interaction between metabolic syndrome and inflammation on cognition (P<0.01-0.09). Metabolic syndrome was negatively associated with cognition in subjects with high inflammation (highest tertile for both CRP and ACT; B values ranging from -0.86 to -1.94, P<0.05), whereas an association was absent in subjects with low inflammation (B values ranging from -0.10 to -0.70). CONCLUSIONS - Subjects with metabolic syndrome showed poorer cognitive performance than subjects without metabolic syndrome, especially those with high levels of inflammation. Hyperglycemia was the main contributor of the association of metabolic syndrome with cognition.