Protective effects of NSAIDs on the development of Alzheimer disease.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD), but observational studies and trials have offered contradictory results. Prior studies have also been relatively short and small. We examined the effects on AD risk of NSAID use for >5 years and of NSAIDs that suppress formation of A beta (1-42) amyloid in a large health care database.


METHODS
Cases were veterans aged 55 years and older with incident AD using the US Veterans Affairs Health Care system. Matched controls were drawn from the same population. NSAID exposure was categorized into seven time periods: no use, <or=1 year, >1 but <or=2 years, and so on. Using conditional logistic regression, adjusted for race and comorbidities, we tested the association between AD development and the use of 1) any NSAID, 2) any NSAID excluding nonacetylated salicylates, 3) each NSAID class, 4) each individual NSAID, and 5) A beta (1-42)-suppressing NSAIDs.


RESULTS
We identified 49,349 cases and 196,850 controls. Compared with no NSAID use, the adjusted odds ratios for AD among NSAID users decreased from 0.98 for <or=1 year of use (95% CI 0.95-1.00) to 0.76 for >5 years of use (0.68-0.85). For users of ibuprofen, it decreased from 1.03 (1.00-1.06) to 0.56 (0.42-0.75). Effects of other NSAID classes and individual NSAIDs were inconsistent. There was no difference between a group of A beta (1-42)-suppressing NSAIDs and others.


CONCLUSIONS
Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. A beta (1-42)-suppressing NSAIDs did not differ from others.
Vlad
Steven C
SC
Boston University School of Medicine, Clinical Epidemiology Research and Training Unit, 650 Albany St., Suite X200, Boston, MA 02118, USA. svlad@bu.edu
Miller
Donald R
DR
Kowall
Neil W
NW
Felson
David T
DT
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D044469:Racial Groups; D017678:Sex Distribution; D013995:Time; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007052:Ibuprofen