BRIEF REPORTS Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research Council Cognitive Function and Ageing Study Chris Fox, à MD, a Kathryn Richardson, à MSc, b Ian D. Maidment, MA, cd George M. Savva, PhD, e Fiona E. Matthews, PhD, f David Smithard, MD, gh Simon Coulton, MSc, d Cornelius Katona, MD, i Malaz A. Boustani, MD, MPH, jklm and Carol Brayne, MD be OBJECTIVES: To determine whether the use of medica- tions with possible and definite anticholinergic activity in- creases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Func- tion and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anti- cholinergic Cognitive Burden Scale and cognition deter- mined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI) 5 0.03–0.64, P 5.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI 5  0.14–0.11, P 5.79). Two- year mortality was greater for those taking definite (OR 5 1.68; 95% CI 5 1.30–2.16; Po.001) and possible (OR 5 1.56; 95% CI 5 1.36–1.79; Po.001) anticholinergics. CONCLUSION: The use of medications with anti- cholinergic activity increases the cumulative risk of cogni- tive impairment and mortality. J Am Geriatr Soc 2011. Key words: anticholinergic activity; cognitive impair- ment; elderly I dentifying risk factors for cognitive decline may lead researchers to a better understanding of clinical interven- tions to reduce the risk of developing Alzheimer’s disease. Less physical, cognitive, and social activity and the presence of diabetes mellitus, hypertension, and hyperlipidemia have been identified as potentially modifiable risk factors for cognitive decline, including incident dementing illnesses such as Alzheimer’s disease. 1 Use of anticholinergic medi- cations has been associated with acute cognitive impair- ment. 2–7 Animal models 8–10 link direct antagonism of the muscarinic cholinergic receptor M1 to decline in cognitive function, but there have been few studies evaluating the long-term exposure to medications as a modifiable risk fac- tor. Progression of Alzheimer’s-type pathology may be amplified with M 1 blockade, 11 whereas enhancing Address correspondence to Dr. Chris Fox, Clinical Senior Lecturer Psychiatry/ Hon Consultant Psychiatrist, School of Medicine, Health Policy and Practice, DeNDRoN Eastern Research Director and Dementia Research Group Chair, University of East Anglia, Norwich, NR4 7TJ, UK. E-mail: chris.fox@uea. ac.uk DOI: 10.1111/j.1532-5415.2011.03491.x à Joint first authors. From the a Department of Psychiatry, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, United Kingdom; b Institute of Public Health, e Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; c Kent and Medway National Health Service and Social Care Partnership Trust, Kent, United Kingdom; d Centre for Health Service Studies, University of Kent, Kent, United King- dom; f Medical Research Council Biostatistics Unit, Cambridge, United Kingdom; g Kent Community Health National Health Services Trust, Ash- ford, United Kingdom h National Institute for Health Research, Maidstone, United Kingdom; i University College London, London, United Kingdom; j Center for Aging Research and k Department of Medicine, l School of Med- icine, Indiana University, Indianapolis, Indiana; m Regenstrief Institute Inc., Indianapolis, Indiana. JAGS 2011 r 2011, Copyright the Authors Journal compilation r 2011, The American Geriatrics Society 0002-8614/11/$15.00