Elsevier

Neurobiology of Aging

Volume 19, Issue 6, November–December 1998, Pages 607-611
Neurobiology of Aging

Original Articles
NSAIDs and incident Alzheimer’s disease. the Rotterdam study

https://doi.org/10.1016/S0197-4580(98)00096-7Get rights and content

Abstract

Recent studies suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer’s disease (AD). We investigated the relation of NSAID use over a 10-year period and the risk for incident AD using a nested case-control design in the population-based Rotterdam Study. The study was performed in 306 subjects; 74 Alzheimer patients diagnosed according to NINCDS-ADRDRA criteria and 232 age and sex-matched controls. NSAID use was abstracted from general practitioners’ medical records and expressed as cumulative prescription days. The relative risk for AD associated with long-term use (≥2 months) was 0.95 (95% CI: 0.46–1.99) as compared to nonusers, after controlling for possible confounders. In a separate examination, subjects who had more than 6 months of prescription days had a reduced relative risk for AD (RR = 0.74 (95% CI: 0.20–2.72). In an age-stratified analysis the effect in long-term users was evident in those aged 85 and under; 0.53 (95% CI: 0.15–1.77). All risk estimates were lower when the last 2 years of exposure were excluded from the analyses. Our point estimates in subjects younger than 85 years and in subjects using NSAIDs for 6 months or more are consistent with the hypothesis that long-term use of NSAIDs reduces the risk for AD. However, overall there was no association between NSAID use and the risk for incident AD.

Section snippets

Study population

The Rotterdam Study is a prospective population-based cohort study of neurological, cardiovascular, locomotor and ophthalmologic diseases in the elderly. All inhabitants of Ommoord, a suburb of Rotterdam in the Netherlands, aged 55 years or more and living in the district for at least 1 year were invited in 1990–1993 to participate in the study. Of the 10,275 eligible subjects, 7,983 (78%) participated and were interviewed at home; 7,129 (89%) of them made two follow-up visits to the research

Results

As a result of matching, the mean age in both groups was almost equal: 85.3 years in cases and 84.7 years in controls (Table 1). There were significantly more female than male sets. Controls had a longer mean exposure than cases. The number of incomplete prescriptions was high, but similar in cases and controls. A significantly higher proportion of cases compared to controls were residents of a nursing home (35.1% vs. 19.3%, p = 0.01) and cases were significantly more often current smokers than

Discussion

In this population-based nested case-control study, overall there was no significant association of NSAID use with the risk for incident AD. However, there was a nonsignificant tendency towards a risk reduction for subjects with at least 6 months of exposure. Furthermore, there was some evidence that a protective effect may be detectable in subjects younger than 85 years.

Several issues of validity need to be discussed when interpreting these results: potential selection bias, information bias

Acknowledgements

We are grateful to staff of the Rotterdam Study Centre for help in the data collection. Furthermore, we thank K. Jacobs and A. Maengkom for collecting the data on NSAID use. We also acknowledge the collaboration with the general practitioners in Ommoord and the RIAGG (Rotterdam Regional Institute for Ambulatory Mental health Care) Noord Rotterdam. This study was made possible by financial support from the NESTOR stimulation program for geriatric research in the Netherlands (Ministry of Health

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