Background: Statin use and type have been variably associated with impaired or improved cognitive performance. Hypothesis: To assess the association of statin use and type (lipophilic vs hydrophilic) and cognitive impairment. Methods: Cross-sectional analysis of 24 595 participants (7191 statin users and 17 404 nonusers) age ≥45 years, from a population-based national cohort study (Reasons for Geographic And Racial Differences in Stroke) enrolled between January 2003 and October 2008, with over sampling from the southeastern Stroke Belt and African Americans. Statin use and type were documented in participants' homes by a trained health professional. Cognitive performancewas assessedwith a prior validated instrument of global cognitive status (Six-Item Screener). Cognitive impairment was defined as a score of <4. Results: Overall, an association of cognitive impairment and statin use was observed (8.6% of users vs 7.7% of nonusers had cognitive impairment, P = 0.014); but, after adjusting for variables known to be associated with cognition (age, gender, race, income, education level, and cardiovascular disease), the association was attenuated (odds ratio [OR]: 0.98, confidence interval [CI]: 0.87-1.10). No association was observed between statin type (lipophilic vs hydrophilic) and cognition (OR: 1.03, CI: 0.86-1.24), and there were no regional differences in cognitive impairment in statin users (8%in the Stroke Belt and 7.9% in other regions, P = 0.63). Conclusions: Statin use and type were marginally associated with cognitive impairment. After adjusting for known variables that affect cognition, no association was observed. No regional differences were observed. This large study found no evidence to support an association between statins and cognitive performance. © 2010 Wiley Periodicals, Inc.