PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Does aspirin protect against Alzheimer’s dementia? A study in a Swedish population-based sample aged ‡80 years Received: 18 November 2002 / Accepted: 7 May 2003 / Published online: 25 June 2003 Ó Springer-Verlag 2003 Abstract Objective: It has been reported that aspirin and other non-steroidal anti-inflammatory drugs (NSAID) may protect against dementia of Alzheimer’s type and/or vascular dementia. However, co-morbidity and the dose of aspirin may be critical. A major indication for low-dose aspirin is prophylaxis after stroke and transient ischaemic attacks, conditions that may obscure an anti-dementia effect by the drug. Alternatively, low-dose aspirin may be insufficient if the protective effect is due to an anti-inflammatory mechanism. The aim of this study was to assess whether high-dose or low-dose aspirin may protect against Alzheimer’s dementia in subjects aged ‡80 years. For comparison, effects of (other) NSAID, paracetamol and D-propoxyphene were studied. Methods: Global, cross-sectional, and longitudinal (1991–2000) epidemiological analyses of clinical, cog- nitive and drug treatment data on 702 individuals 80 years old or more (351 twin pairs of same sex), all alive at inclusion: mean age 83.9 years (80–99 years). Calculations were made with logistic regression of associations between use of various analgesics and cognitive function, after adjustment for age, gender, and cardiovascular and cerebrovascular diseases. Results: Users of high-dose aspirin had significantly lower prevalence of Alzheimer’s dementia and better- maintained cognitive function than non-users. There were numerically similar but not significant associations with use of low-dose aspirin and other NSAID. There were no such associations with use of either paracetamol or D-propoxyphene. Conclusion: Aspirin might protect against Alzheimer’s disease, but controlled trials are warranted. Keywords Aspirin Æ NSAID Æ Alzheimer Introduction It has been speculated that aspirin (acetylsalicylic acid) and other non-steroidal anti-inflammatory drugs (NSAID) may prevent dementia of Alzheimer’s type and/or vascular dementia [1, 2, 3, 4, 5]. A Cochrane report [6] has stated that there is no evidence of a protective effect of aspirin in vascular dementia. However, co-morbidity and the dose of aspirin may be critical for the prognosis on cognitive decline. A major indication for low-dose aspirin treatment is prophylaxis after stroke and transient ischaemic attacks (TIAs). These conditions may obscure a neuroprotective effect by low-dose aspirin. Alternatively, if the mechanism of the anti-dementia effect is anti-inflammatory, low-dose aspirin may be insufficient to produce a discernable treatment effect. The current observational study compared the possible neuroprotective effects of different dose regi- mens of aspirin and of non-aspirin NSAID, paraceta- mol (acetaminophen) and D-propoxyphene, in a Swedish population-based cohort of individuals 80 years old or more. Eur J Clin Pharmacol (2003) 59: 313–319 DOI 10.1007/s00228-003-0618-y Sven E. Nilsson Æ Boo Johansson Æ Sanna Takkinen Stig Berg Æ Steven Zarit Æ Gerald McClearn Arne Melander S. E. Nilsson Æ B. Johansson Æ S. Takkinen Æ S. Berg Institute of Gerontology, School of Health Sciences, Jo¨nko¨ping University, Jo¨nko¨ping, Sweden B. Johansson Department of Psychology, Go¨teborg University, Go¨teborg, Sweden S. Zarit Gerontology Center, Pennsylvania State University, University Park, PA, USA G. McClearn Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA A. Melander (&) The NEPI Foundation and Department of Community Medicine, Medical Research Centre, Malmo¨ University Hospital, Lund University, 205 02 Malmo¨, Sweden E-mail: arne.melander@nepi.net Tel.: +46-40-331971 Fax: +46-40-337306