Abstract
Alzheimer disease (AD) mortality risk in a large cohort of subjects treated or not with non-steroidal anti-inflammatory drugs (NSAIDs) is unknown. Our objective was to determine whether NSAIDs use is associated with decreased risk of AD mortality. In this prospective, population-based study (Neurological Disorders in Central Spain [NEDICES]) of 5,072 people without AD (aged 65 years and older), sociodemographic, comorbidity factors, and current medications were recorded at baseline. Community-dwelling older adults were followed for a median of 12.7 years, after which the death certificates of deceased participants were examined. 2,672 (52.7%) of 5,072 participants died, including 504 (18.9%) NSAIDs users and 2,168 (81.1%) non-users. Of the 2,672 deceased participants, 113 (4.2%) had AD as a cause of death (8 [1.6%] among NSAIDs users and 105 [4.8%] among non-users, chi-square = 10.70, p = 0.001). In an unadjusted Cox model, risk of AD mortality was decreased in NSAIDs users (hazard ratio [HR] for AD mortality = 0.35, 95% confidence interval [CI] 0.17–0.72, p = 0.004) when compared to non-users. After adjusting for numerous demographic factors and co-morbidities, the HR for AD mortality in NSAIDs users was 0.29, 95% CI 0.12–0.73, p = 0.009. Stratified analyses showed a significantly decreased risk of AD mortality with aspirin, whereas non-aspirin NSAIDs only showed a statistical trend toward significance in the adjusted Cox regression models. NSAIDs use was associated with 71% decreased risk of AD mortality in older adults. Our results support the hypothesis that NSAIDs use is a protective factor of developing AD.
Highlights
The development and evaluation of new therapies to slow the progression of Alzheimer’s disease (AD) is a public health priority
Notwithstanding, interest in non-steroidal anti-inflammatory drugs (NSAIDs) has been sparked in AD research by the notion that these medications might have a mode of action beyond inflammation; their neuroprotective effects might be mediated by alteration of oxidative phosphorylation and possibly the ribosome pathway,[6] as well as inhibition of mitochondrial Ca2+ overload.[7]
The results of the current study suggest that non-AD older adults taking NSAIDs are at decreased risk of AD mortality
Summary
The development and evaluation of new therapies to slow the progression of Alzheimer’s disease (AD) is a public health priority. It is an exciting time as some traditional drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), and many others in development. Oxidative stress has long been considered as a component of the many pathophysiological events of AD.[8]
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