Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study.
BACKGROUND
Previous analyses from the Cache County (UT) Study showed inverse associations between the prevalence of AD and the use of nonsteroidal anti-inflammatory drugs (NSAID), aspirin compounds, or histamine H(2) receptor antagonists (H(2)RA). The authors re-examined these associations using data on incident AD.


METHODS
In 1995 to 1996, elderly (aged 65+) county residents were assessed for dementia, with current and former use of NSAID, aspirin, and H(2)RA as well as three other "control" medication classes also noted. Three years later, interval medication histories were obtained and 104 participants with incident AD were identified among 3,227 living participants. Discrete time survival analyses estimated the risk of incident AD in relation to medication use.


RESULTS
AD incidence was marginally reduced in those reporting NSAID use at any time. Increased duration of use was associated with greater risk reduction, and the estimated hazard ratio was 0.45 with >/=2 years of exposure. Users of NSAID at baseline showed little reduction in AD incidence, regardless of use thereafter. By contrast, former NSAID users showed substantially reduced incidence (estimated hazard ratio = 0.42), with a trend toward greatest risk reduction among those with extended exposure. Similar patterns appeared with aspirin but not with any other medicines examined.


CONCLUSIONS
Long-term NSAID use may reduce the risk of AD, provided such use occurs well before the onset of dementia. More recent exposure seems to offer little protection. Recently initiated randomized trials of NSAID for primary prevention of AD are therefore unlikely to show effects with treatment until participants have been followed for several years.
Zandi
Peter P
PP
Department of Mental Hygiene, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Anthony
James C
JC
Hayden
Kathleen M
KM
Mehta
Kala
K
Mayer
Lawrence
L
Breitner
John C S
JC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D001241:Aspirin