Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia

Jordan, Fionnuala; Quinn, Terry; Passmore, Peter; Kelly, John; Smith, Catrin Tudur; Murphy, Kathy; Devane, Declan

doi:10.1002/14651858.cd011459.pub2

Cited by 50 publications

(44 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aspirin 75–300 mg daily has been widely used for secondary prevention of thrombotic cerebrovascular and cardiovascular disease over the past three decades. Low-dose aspirin is generally defined as 75–100 mg/day (Rands and Orrell, 2000 ; Jordan et al, 2020 ). Its biological actions involving anti-inflammatory and anti-thrombotic properties play an important role in several diseases (Marquis-Gravel et al, 2019 ; Zheng and Roddick, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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

Wan

Zhang³

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Wan

Zhang³

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Epidemiological studies of non-steroidal anti-inflammatory drug (NSAID) interventions have suggested their use may delay disease onset [10,11] providing support for inflammation in the aetiology of AD. A meta-analysis study has revealed as much as 50% reduction in the risk of disease onset among chronic none steroidal anti-inflammatory drugs (NSAID) users [12].…”

Section: Commentarymentioning

confidence: 99%

“…The positive outcome of a number of small (n~50) pilot intervention studies over 3-6 months to address the hypothesis that chronic NSAID use can prevent or delay the rate of cognitive decline in AD patients has led to the establishment of clinical trials [14]. However, large-scale double-blind placebo-controlled clinical trials have not supported the use of NSAIDS in treating established AD [11]. The disappointing outcome of these clinical trials has raised questions as to our understanding of mechanisms and pathways that link systemic inflammation and neurodegeneration, and prompted questions about whether NSAIDs can act only as preventative agents following long term use, and whether their clinical failure to treat established AD has resulted from inappropriate choices of NSAIDs and the doses employed.…”

Section: Commentarymentioning

confidence: 99%

Current and Future Directions for Targeting Lipoxin A4 in Alzheimer’s Disease

Dias

Griffiths

2021

JAD

View full text Add to dashboard Cite

Neuroinflammation has been implicated in Alzheimer’s disease onset and progression. Chronic neuroinflammation is initiated by amyloid-β-activated microglial cells that secrete immuno-modulatory molecules within the brain and into the vasculature. Inflammation is normally self-limiting and actively resolves by “switching off” the generation of pro-inflammatory mediators and by non-phlogistic clearance of spent cells and their debris to restore tissue homeostasis. Deficits in these anti-inflammatory/pro-resolution pathways may predispose to the development of chronic inflammation. The synthesis of endogenous lipid mediators from arachidonic acid, lipoxins via cyclooxygenase 2 and lipoxygenases, and conversion of exogenous polyunsaturated fatty acids, namely docosahexaenoic acid and eicosapentaenoic acid, to resolvins contributes to effective, timely resolution of acute inflammation. Work by Xiuzhe et al., 2020 in the Journal of Alzheimer’s Disease reported that plasma level of LXA4 is related to cognitive status in ischemic stroke patients suggesting that decreased LXA4 may be a potential risk factor for post post-stroke cognitive impairment. As evident by recent clinical trials and development of drug analogues, there is recent drive to search for lipoxin analogues as therapeutics for inflammatory diseases. Understanding how bioactive lipid signaling is involved in resolution will increase our understanding of controlling inflammation and may facilitate the discovery of new classes of therapeutic pro-resolution agents for evaluation in AD prevention studies.

show abstract

“…However, a Cochrane review in 2012 concluded that the efficacy of aspirin, steroid and aspirin, steroidal and nonsteroidal anti‐inflammatory drugs (NSAIDs), and selective cyclooxygenase‐2 (COX‐2) inhibitors in AD is not proven and did not recommend these drugs for the treatment of AD 63 . Another Cochrane review in 2020 also concluded that there was no evidence to support the use of low‐dose aspirin, traditional NSAIDs, or selective COX‐2 inhibitors for the prevention of dementia, but there was evidence of harm 64 . These data indicated that simple anti‐inflammation therapeutic strategies for AD should be reconsidered, although inflammatory and immune processes have been suspected in AD pathogenesis.…”

Section: Dementia and Neuroinflammationmentioning

confidence: 99%

Neuroimmunology in neurological and psychiatric disorders

Takeuchi

2021

Clinical & Exp Neuroim

View full text Add to dashboard Cite

The central nervous system (CNS) has long been considered as an immunological privileged site where the surveillance of the immune system does not reach out. However, it is now recognized that this CNS homeostasis is collapsed by neuroinflammation such as influx of proinflammatory factors and cells, neuronal dysfunction, and glial activation. Currently, CNS neuroinflammation is considered as a main pathomechanism to mediate disease progression in not only neurotrauma and neuroinflammatory disorders but also neurodegenerative diseases including dementia. Moreover, growing evidence indicates that chronic CNS neuroinflammation is also involved in the pathogenesis of psychiatric disorders such as autism spectrum disorders, depression, and schizophrenia. This paper reviews the current proposed pathomechanisms and therapeutic strategies of neurological and psychiatric disorders from a point of view of chronic neuroinflammation.

show abstract

Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia

Cited by 50 publications

References 82 publications

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

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

Current and Future Directions for Targeting Lipoxin A4 in Alzheimer’s Disease

Neuroimmunology in neurological and psychiatric disorders

Contact Info

Product

Resources

About