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AlzRisk Paper Detail

Reference: Szekely, 2008
Cohort: Cardiovascular Health Cognition Study/Cardiovascular Health Study Cognition Study
Risk Factor: Non-Steroidal Anti-Inflammatory Drugs

Average Follow-up Time Detail
The study cohort included CHCS participants who were recruited between 1989 and 1991 and who underwent an MRI examination between 1991 and 1994. Participants in the CHCS underwent annual examinations as well as a detailed clinical examination in 1999.

Exposure Detail
Interviewers ascertained exposure information by visual inspection at annual visits, in which participants were asked to report and bring all vials for medications taken within 14 days of the visit. The investigators reported results separately for ever vs. never non-ASA NSAID use and ever vs. never ASA NSAID use. This entry pertains to results on ever vs. never non-ASA NSAID use.

The investigators compared incident AD risk in two groups: the group of participants who used non-ASA NSAIDs at any time ("Ever used") and the reference group of participants who did not use non-ASA NSAIDs at any time up to the follow-up visit ("Never used"). The exposure information was time-varying, so a participant could have been a "never user" at an earlier follow-up visit, but could change to a "ever user" at a later follow-up visit.

Age Detail
All participants were at least 65 years old. Approximately half of the participants were 75 years old or younger at baseline, and half were older than 75 years old at baseline.

Screening and Diagnosis Detail
Screening Method:
3MSEModified Mini-Mental State Examination (Teng 1987)

AD Diagnosis:
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"Chronological age was used as the time axis, and follow-up began after the baseline visit. Follow-up ended at the midpoint in the year of dementia onset for cases, or at the date of death or last follow-up visit for noncases. Reports of medication use (NSAIDs, aspirin, and acetaminophen) were categorized as ever vs never and were modeled as time-dependent variables."

"Subsequent analyses focused on the NSAID medication class and AD outcome only. To help control for changes in drug reporting immediately before diagnosis, and to investigate potential lag effects of NSAID exposure on AD risk, models with “lagged” exposure of 1 and 2 years were examined. In these models, the exposure status (NSAID use or no NSAID use) for each visit was assigned the value from the prior visit (either 1 or 2 years before) to help account for the lag or delay of effect of drug exposure.10 Duration of NSAID use was examined by calculating a cumulative, time-varying variable that was then operationalized in different models as a continuous variable or dichotomized into ≤2 years of use and >2 years of use, as has been done in previous studies of NSAIDs and AD.4,10,13 We calculated dose equivalencies between different NSAIDs by converting the daily dose of each NSAID to a proportion of the maximum daily dose reported on product monographs. Using this standardized dose, we were able to add NSAIDs if more than one type (e.g., ibuprofen and naproxen) was taken at one visit, and we were able to calculate the maximum dose each participant took during the course of observation. Cumulative dose was then captured in separate models as a continuous variable or a categorical variable, with cut points guided by typical dosing of NSAIDs and the distribution of use in the sample. We also investigated use of prescription NSAIDs only, because use by prescription may be more regular or in higher dosage. For the latter analysis, the baseline was taken as the MRI visit because information on prescription medications (but not OTC) was available at that visit."

Analysis were also stratified by baseline age, apolipooprotein E status and race.

"There was no consistent evidence of greater reduction in risk of AD with lagging of exposure, longer duration of use, or higher doses of NSAIDS. The above analyses were repeated, considering prescription NSAID use only, and the results were similiar."

AD Covariates:
APOE4APOE e4 genotype
MMSEbaseline MMSE

TD Covariates:
APOE4APOE e4 genotype
MMSEbaseline MMSE