Anti-inflammatory drugs protect against Alzheimer disease at low doses

Context: Anti-inflammatory medications have an inverse association with Alzheimer disease (AD). Objectives: To examine at what doses this anti-inflammatory drug effect occurs and whether other medications and/or International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses affect the association. Design: Subjects 75 years and older from a random population sample were classified by consensus using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses. Drug associations with different types of dementia with and without the International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses as well as dosage data were analyzed. Setting: The Centre for Education and Research on Aging, Concord Hospital, Concord, Australia. Patients: The Sydney Older Persons Study recruited 647 subjects (average age, 81 years). A total of 163 patients were given diagnoses placing them in different dementia categories and were compared with 373 control subjects. Of the patients with dementia, 78 had AD without vascular dementia, 45 had vascular dementia (permissive of other dementia diagnoses), and 40 had other dementia diagnoses (without AD or vascular dementia). Main Outcome Measures: Fifty drugs or drug groups were subjected to a 2 (drug used vs drug not used) x 4 (dementia and control groups) chi (2) analysis. Drugs with inverse associations were identified and potential confounders (logistic regression) and dosage data (exact small sample 1-tailed tests) analyzed. Results: As expected, there was an inverse association between nonsteroidal anti-inflammatory drugs and aspirin (and unexpectedly angiotensin-converting enzyme inhibitors) and AD. This association was not observed with vascular dementia or any other diagnoses. Analysis showed no evidence for a dosage effect, ie, responses were equivalent for low and high doses. Conclusions: This study does not support a high-dose anti-inflammatory action of nonsteroidal anti-inflammatory drugs or aspirin in AD. Potential mechanisms for the beneficial effects of these medications are discussed.