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AlzRisk Paper Detail

Reference: Szekely, 2008b
Cohort: Six Pooled Cohorts
Risk Factor: Non-Steroidal Anti-Inflammatory Drugs

Average Follow-up Time Detail
The average follow-up time is not provided for the six cohort studies. However, calendar years of data collection are: BLSA (1980-1995), CCS (1994-1999), CSHA (1991-1997), CHS (1992-1998), FHS (1990-2001), and MoVIES (1987-2001).

Exposure Detail
The interviewers ascertained exposure information by self-report. In all studies, there was an in-person structured interview except for the CSHA study, in which there was a self-administered questionnaire. In addition, the information was corroborated by viewing pill bottles for the CCS, CHS, and MoVIES studies. The investigators reported results separately for ever vs. never non-ASA NSAID use, ever vs. never non-ASA NSAID use by SALA categorization, and ever vs. never ASA NSAID use. This entry pertains to results on ever vs. never non-ASA NSAID use by SALA categorization.

The investigators compared incident AD risk in four groups: the group of participants who only used SALAs at any time ("SALA use"), the group of participants who only used non-SALAs at any time ("Non-SALA use"), the group of participants who used both SALAs and non-SALAs at any time ("SALA and non-SALA use), 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.

Ethnicity Detail
The BLSA, CCS, CSHA were composed of predominately white participants, and the CHS cohort had African Americans recruited from three of the four counties. The distribution of ethnicity was not reported for FHS and MoVIES.

Age Detail
The mean or the median age at the start of follow-up was not reported. However, the following is the age distribution for all six cohorts combined: 1080 (8.0%) were less than 65 years old, 2569 (19.0%) were between 65-69.99 years old, 3950 (29.3%) were between 70-74.99 years old, 3311 (24.5%) were between 75-79.99 years old, and 2589 (19.2%) were at least 80 years old.

Screening and Diagnosis Detail
AD Diagnosis:
Brain Imaging
DSM IIIR Diagnostic and Statistical Manual III-Revised
DSM IV Diagnostic and Statistical Manual IV
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)
Neurologic examination

All studies assessed probable and possible AD. The diagnosis of AD was made using DSM-III-R and NINCDS-ADRDA for the BLSA, CCS, CSHA, and MoVIES cohorts; for the CHS and FHS cohorts, the diagnosis of AD was made using DSM-IV and NINCDS-ADRDA. Expert clinicians of consensus conferences made the diagnoses after review of neurocognitive assessments, detailed clinical evaluations, neuroimaging, and laboratory tests.

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"For the pooled participant analysis we pooled individual-level study data and used extended Cox hazards regression (29) to obtain crude and adjusted hazard ratios (aHRs) with 95% CIs for the association between incident AD and three medications groups: non-aspirin NSAIDs, aspirin, and acetaminophen. In turn, we examined separate models with SALA or non-SALA NSAIDs. All models used chronological age at observation as the time axis (to provide tight control of potential confounding by age), and medication use was modeled as ever-used vs never-used as a time-dependent covariate. Thus, a participant who entered the analysis as a “never user” could later switch to an “ever user” if NSAID use was initiated during follow-up. To account for potential variability in baseline hazards between studies we stratified all analyses by study. We further adjusted by sex, education, and age at first visit (to additionally control for possible cohort effects). In addition, we used self-report of arthritis as a covariate in the model looking at any NSAID use."

AD Covariates:
SPstudy population