NSAID Exposure and Risk of Alzheimer's Disease: An Updated Meta-Analysis From Cohort Studies

Abstract

Background: Initial observational studies and a systematic review published recently have suggested that non-steroidal anti-inflammatory drug (NSAID) use has the trend to be associated with reduced risk of Alzheimer's disease (AD), while results remain conflicting. Thus, we performed an updated meta-analysis to reevaluate the evidence on this association.Methods: Data sources from PUBMED, Embase and Cochrane Library from inception through April 2017 were searched by two independent reviewers. Eligible cohort studies were selected according to predefined keywords. We did a meta-analysis of available study data using a random-effects model to calculate overall relative risks (RRs) for associations between NSAID exposure and AD risk.Results: From 121 potentially relevant studies, 16 cohort studies including 236,022 participants, published between 1995 and 2016, were included in this systematic review. Meta-analysis demonstrated that current or former NSAID use was significantly associated with reduced risk of AD (RR, 0.81, 95% CI0.70 to 0.94) compared with those who did not use NSAIDs. This association existed in studies including all NSAID types, but not in aspirin (RR, 0.89, 95% CI 0.70 to 1.13), acetaminophen (RR, 0.87, 95% CI 0.40 to 1.91) or non-aspirin NSAID (RR, 0.84, 95% CI 0.58 to 1.23).Conclusions: Current evidence suggests that NSAID exposure might be significantly associated with reduced risk of AD. However, further large-scale prospective studies are needed to reevaluate this association, especially the associations in individual NSAID type.

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

“…This assumption is reinforced by several cohort analyses. A recent meta-analysis including 16 investigations demonstrate that present or previous utilization of NSAIDs is linked to a decreased relative risk of AD (0.81; 95% confidence interval, 0.70-0.94) (206). Despite the observational epidemiological data suggesting a protective effect of NSAIDs and the evidence for a biologically plausible role for anti-inflammatory treatment, all placebo-controlled trials of a wide range of anti-inflammatory agents (NSAIDs, corticosteroids, and others) in both mild-tomoderate AD patients ( Table 1) and MCI subjects ( Table 2) are negative.…”

Receptors for pro‐resolving mediators are increased in Alzheimer's disease brain

“…Neuroinflammation has received increasing attention in the AD field with a potential for development of novel drug therapies that can prevent accumulation of AD pathologies. Because completely blocking inflammation may not be the best solution [see eg, (91)], we have focused on the end of inflammation-the resolution process.…”

Predicting the potency of anti-Alzheimer drug combinations using machine learning

“…The ten-best combinations of the eleven drugs that excluded drugs acting on the brain and/or psychological level included NSAID, anticoagulant, lipid-lowering, and antihypertensive drugs, as well as estrogen/progestin. Drugs from all of these categories have been shown to reduce AD risk, however they all show disappointing results when used singly in clinical trials [33][34][35][36][37][38][39][40][41][42][43][44][45]. The use of combinations of these and other drugs remains an attractive option [7][8][9][10][11].…”