Aspirin Use on Incident Dementia and Mild Cognitive Decline: A Systematic Review and Meta-Analysis

Abstract

Background: More people with cognitive dysfunction and dementia also fall into the category of high vascular risk, for which aspirin is one of the most frequently used drugs. However, previous studies reporting that aspirin buffers against mild cognitive decline (MCI) and dementia remain controversial. We thus conducted an updated systematic review and meta-analysis to evaluate the association of aspirin use with the risk of MCI and dementia in older adults.Methods: Data sources from PubMed, Embase, Web of Science, and the Cochrane Database for randomized controlled trails (RCTs) and cohort studies (published between January 1, 2000 and April 11, 2020). Relative risks (RRs) and 95% confidence intervals (95% CIs) were used to pool data on the occurrence of dementia and MCI with random-effects models.Results: Of 3,193 identified articles, 15 studies (12 cohort studies and three RCTs) were eligible and were included in our analysis, which involved a total of 100,909 participants without cognitive dysfunctions or dementia at baseline. In pooled cohort studies, aspirin use did not reduce the incidence of MCI and dementia (the pooled RR = 0.97; 95% CI = 0.85–1.11; Ifor heterogeneity2 = 65%) compared with non-users. However, low-dose aspirin (75–100 mg/day) was associated with a decreased likelihood of developing dementia or MCI (the pooled RR = 0.75; 95% CI = 0.63–0.9; Ifor heterogeneity2 = 50.5%). This association existed in studies including all-cause dementia (the pooled RR = 0.82; 95% CI = 0.71–0.96) and Alzheimer's disease (AD) (the pooled RR = 0.54; 95% CI = 0.33–0.89), but not in MCI (the pooled RR = 0.58; 95% CI = 0.31–1.08). In RCTs, low-dose aspirin use was not significantly associated with less prevalence of dementia or MCI (RR = 0.94; 95% CI = 0.84–1.05; Ifor heterogeneity2 = 0.0%).Conclusions: In cohort studies, we found that low-dose aspirin use had a higher likelihood of reducing the incidence of dementia, which was not supported by RCTs. The evidence was insufficient to fully evaluate the effect of aspirin on cognitive function and dementia. Well-designed studies and innovative approaches are therefore needed to clarify whether the use of aspirin improves cognitive function and reduces the risk of dementia.

Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia

“…Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been suggested both for the prevention of Alzheimer’s disease (AD) [47] and for the treatment of schizophrenia [48], due to the emerging evidence of excessive inflammatory response in the pathophysiology of both schizophrenia [48] and AD [47]. For the prevention of dementia, evidence is insufficient to fully evaluate the effect of aspirin on cognitive decline and risk of dementia [49,50]. Results from clinical trials investigating effects of adding aspirin to standard antipsychotic treatment in schizophrenia are inconclusive [51,52].…”

Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer’s disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

“…A systematic review by H. Li et al summarized the literature up to April 2020 and we checked in Pubmed that there were no further studies on LDASA use and dementia outcomes as of August 2021. 7 Overall, a meta-analysis of 8 studies indicated that the use of any dose of ASA did not significantly decrease the risk of developing dementia (pooled relative risk (RR) [95% CI]: 0.94 [0.77 to 1.16]. However, when the authors restricted the meta-analysis to 4 studies with LDASA exposure and the outcome all-cause dementia 39-42 and 2 studies with LDASA exposure and the outcome AD, 40 41 LDASA use showed a protective effect against all-cause dementia (pooled RR [95% CI]: 0.82 [0.71 to 0.96]) and AD (pooled RR [95% CI]: 0.54 [0.33 to 0.89]).…”

“…The latest systematic review of randomized controlled trials (RCT) on the topic was also performed by H. Li et al and included two RCTs – both published in 2020. 7 In the RCT by Matsumoto et al 44 , 2,536 diabetes patients (age 30–85 years; median: 65 years) without CVD were randomized into receiving LDASA (81 or 100 mg) and were followed over a median of 11.4 years. A tendency towards reducing all-cause dementia risk was observed, but the result was not statistically significant (HR [95%CI]: 0.82 [0.58 to 1.16]).…”

“…6 Systematic reviews and meta-analyses of observational studies but not randomized controlled trials (RCTs) supported the possibility that low-dose acetylsalicylic acid (LDASA) could protect against dementia. 7 8 However, no population-based, observational cohort study has been performed so far. Studies with long follow-up are especially needed because it has been observed that NSAID use might only protect against AD when initiated long before cognitive decline begins.…”

A mild dose of aspirin promotes hippocampal neurogenesis and working memory in experimental ageing mice

“…Among various COX-2 inhibitors, aspirin has been speculated to enhance memory in ageing population and mitigate neuropathogenesis in various brain diseases. While some correlative studies indicated that the association between aspirin treatment and memory is uncertain, ample scienti c evidence strongly implies that aspirin prevents memory decline in elderly subjects [13,14]. Eventually, recent reports demonstrated that aspirin treatment considerably improves the synaptic plasticity in the cognitive centres of the experimental brains [15].…”