OBJECTIVES:To prospectively relate C-reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1-year follow-up period. DESIGN:Prospective 1-year follow-up. SETTING:Outpatient university medical setting. PARTICIPANTS:Seventy-eight adults (aged 56-84; 39% female) with cardiovascular disease. MEASUREMENTS:CRP levels were measured using a high-sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later. RESULTS:The association between CRP and change in cognition over the 1-year follow-up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention-executive-psychomotor). High CRP levels were associated with subtle declines in attention-executive-psychomotor performance (CRP beta=-0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance. CONCLUSION:These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention-executive-psychomotor performance.