ELSEVIER Relation of Prescription Nonsteroidal Antiinflammatory Drug Use to Cognitive Function among Community-Dwelling Elderly JOSEPH T. HANLON, PHARMD, KENNETH E. SCHMADER, MD, LAWRENCE R. LANDERMAN,PHD, RONNIE D. HORNER, PHD, GERDA G. FILLENBAUM, PHD, CARL F. PIEPER, DRPH, WILLIAM E. WALL JR., RA, MICHAEL J. KORONKOWSKI, PHARMD ,* AND HARVEY JAY COHEN, MD PURPOSE: To evaluate the relationship of nonsteroidal antiinflammatory drug (NSAID) use to lr~cl of cognitive function in community-dwelling elderly persons. METHODS: The prospective cohort study included 2765 nonproxy subjects from the Duke Universrty Established Populations for Epidemiologic Studies of the Elderly who were cognitively intact at baseline (1986-1987) and alive at follow-up three year later. Cognitive function was assessed by the Shrlrt Portable Mental Status Questionnaire (i.e., intact vs. impaired and change in score) and by the individual domains of the Orientation-Memory-Concentration Test (i.e., number of errors). NSAID use, determined from in-home interviews, was coded for chronicity, dose, frequency of use, and prescription status. RESULTS: After controlling for demographic factors as well as health sratus and behavior, continuous. regularly-scheduled, prescription use of NSAID was associated with preservation of one aspect of cognitr ve functioning: concentration (beta coefhcient, 0.29; 95% confidence interval [CI] -0.54 to -0.04, indicating fewer errors). However, no consistent dose-response relationship was found. Current and prior NSAID use was unrelated to level of cognitive functioning across all five measures; among current users, those taking moderate or high doses (beta coefficient, 0.41; 95% CI, 0.08 to 0.74) made more errors on the memory test compared with those taking low doses (beta coefficient 0.03; 95% CI, -.85 to 0.91). CONCLUSIONS: These results suggest no substantial or consistent protective effect of prescription NSAID use on cognitive function in community-dwelling elderly. However, recent use at higher doses may be associated with memory deterioration in this population. Ann EpidemioE 1997;7:87-c-14. 0 1997 by Elsevier Science Inc. KEY WORDS: Nonsteroidal; antiinflammatory agents, cohort studies; cognition; aged; memory. INTRODUCTION Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most frequently prescribed classes of medication in the United States, and these drugs are more likely to be pre- scribed for the elderly than for younger persons (l-3). Be- From the Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC (J.T.H., K.E.S, L.R.L., R.D.H., G.G.F., C.F.P., W.E.W., H.J.C.,); Department ofMedicine, Duke Universtty Medical Center, Durham, NC (J.T.H., K.E.S., R.D.H., H.J.C.); Department of Community and Family Medicine (Division of Biometry), Duke University Medical Center, Durham, NC (C.F.P.); Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC (L.R.L., G.G.F.); Center for Health Services Reseach in Primary Care (J.T.H., K.E.S., R.D.H.); Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Durham, NC (J.T.H., K.E.S., H.J.C.); and the School of Pharmacy, University ofNorth Carolina, Chapel Hill, NC (J.T.H., M.J.K.). Address reprint requests to: Joseph T. Hanlon, Pharm. D., Center for the Study of Aging and Human Development, Box 3003, Duke University Medical Center, Durham, NC 27710. *Current address: Division of Pharmacy Practice, School of Pharmacy, University of Illinois, (M/C 833) South Woods St. Chicago, IL 60612. This work was presented in part at the American Geriatrics Society Annual Meeting, Washington, D.C., May, 1995. Received April 4, 1996; accepted September 10, 1996. 0 1997 by Elsevier Science Inc. hi5 Avemw oi the Americas, New York, NY 10010 tween 10 and -15% of community-dwelling elderly utilize nonaspirin NSAIDs (4,5) and the old-old (i.e., 75 years and older) are more likely to be chronic users of these medications (6). An important reason for the prevalent use ofNSAID is that they effectively treat the acure and chronic pain disorders ~‘3common in this age group (7-9). Investigators have demonstrated diverse central nervous system effects of NSAID use in the elderly: deleterious, protective, or no effects (10-28). Case reports suggest that high-dose indomethacin and sulindac cause psychosis and delirium (18,19) and that naproxen and ibuprofen cause or exacerbate cognitive impairment (20). Alternatively, it has been suggested ,that the use of NSAIDs may protect against the development of severe cognitive impairment due to Alzheimer’s disease (21,22). A report by Breitner et al. (23) indicated :an inverse association between Alzheimer’s diseaseand dailv use of NSAIDs or any use of corticosteroids. A case control :jtudy from Canada found that NSAID users were 45% less hkely to have Alzheimer’s disease than those unexposed to these drugs (24). In contrast, a case-control study with precise exposure information derived from cotn- puterized pharmacy records (as opposed to retrospective self- report) found no significant association between NSAID use and Alzheimer’s disease (25). Finallv. TWO experimental