Relationship of Anticoagulant Therapy With Cognitive Impairment Among Patients With Atrial Fibrillation: A Meta‐Analysis and Systematic Review

Cheng, Wenke; Liu, Weijun; Li, Bin; Li, Dongfang

doi:10.1097/fjc.0000000000000575

Cited by 57 publications

(56 citation statements)

References 27 publications

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“…The findings from this study are in line with a recent meta-analysis (Cheng et al, 2018), which was based on five studies and suggested there was an association between anticoagulant use and reduced incidence of dementia. However, the limitations of previous meta-analysis were the results relied on cross sectional studies, which may introduce bias and confounding, and the effects of VKA alone versus no treatment on dementia were not examined.…”

Section: Discussionsupporting

confidence: 91%

Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials

Mongkhon

Naser

Fanning

et al. 2019

Neuroscience & Biobehavioral Reviews

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Atrial fibrillation (AF) is a documented risk factor for dementia. However, it is unclear whether oral anticoagulant (OAC) treatment can reduce the development of dementia or cognitive impairment. We conducted a systematic review and meta-analysis of the association between OAC use and subsequent dementia development in AF patients by searching databases from their inception to February 2018 without language restriction. Six studies (one randomized controlled trial and five observational studies) met the inclusion criteria. The pooled adjusted risk ratios (RRs) suggested a protective effect of OAC use in reducing dementia risk (RR 0.79 [95% CI: 0.67-0.93], I 2 =59.7%; P=0.005). Further, high percentage of time in therapeutic range (TTR) was associated with a decreased risk of dementia (RR 0.38 [95% CI 0.22-0.64], I 2 =81.8%; P<0.001). Our results support the hypothesis that AF-related dementia may be due to silent brain infarcts and micro-embolism that could be prevented by OAC use. Future studies with prospective follow-up with direct comparison of vitamin K antagonists and direct oral anticoagulants are needed.

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Section: Discussionsupporting

confidence: 91%

Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials

Mongkhon

Naser

Fanning

et al. 2019

Neuroscience & Biobehavioral Reviews

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“…The evidence supporting a direct connection between AF and dementia suggests the possibility that anticoagulant therapy for AF may reduce the incidence of dementia in this population, and results obtained in a number of recent population-based studies suggest that this is indeed the case (Ding et al, 2018;Field et al, 2019;Mongkhon et al, 2019;Silva et al, 2019). Interestingly, while some groups have found that all anticoagulants provide a level of protection (Friberg and Rosenqvist, 2018) most studies report that the direct oral anticoagulants (DOACs) that target thrombin are particularly efficacious (Jacobs et al, 2016;Chen et al, 2018;Cheng et al, 2018). It is tempting to conclude that DOACs reduce the risk of AF-related dementia by decreasing the incidence of thrombotic and/or embolic events, but this scenario may be overly simplistic.…”

Section: Inhibiting Thrombin: Implications For Therapeutic Interventimentioning

confidence: 99%

Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer’s Disease

2020

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The societal burden of Alzheimer's disease (AD) is staggering, with current estimates suggesting that 50 million people worldwide have AD. Identification of new therapeutic targets is a critical barrier to the development of disease-modifying therapies. A large body of data implicates vascular pathology and cardiovascular risk factors in the development of AD, indicating that there are likely shared pathological mediators. Inflammation plays a role in both cardiovascular disease and AD, and recent evidence has implicated elements of the coagulation system in the regulation of inflammation. In particular, the multifunctional serine protease thrombin has been found to act as a mediator of vascular dysfunction and inflammation in both the periphery and the central nervous system. In the periphery, thrombin contributes to the development of cardiovascular disease, including atherosclerosis and diabetes, by inducing endothelial dysfunction and related inflammation. In the brain, thrombin has been found to act on endothelial cells of the blood brain barrier, microglia, astrocytes, and neurons in a manner that promotes vascular dysfunction, inflammation, and neurodegeneration. Thrombin is elevated in the AD brain, and thrombin signaling has been linked to both tau and amyloid beta, pathological hallmarks of the disease. In AD mouse models, inhibiting thrombin preserves cognition and endothelial function and reduces neuroinflammation. Evidence linking atrial fibrillation with AD and dementia indicates that anticoagulant therapy may reduce the risk of dementia, with targeting thrombin shown to be particularly effective. It is time for "outside-the-box" thinking about how vascular risk factors, such as atherosclerosis and diabetes, as well as the coagulation and inflammatory pathways interact to promote increased AD risk. In this review, we present evidence that thrombin is a convergence point for AD risk factors and as such that thrombin-based therapeutics could target multiple points of AD pathology, including neurodegeneration, vascular activation, and neuroinflammation. The urgent need for disease-modifying drugs in AD demands new thinking about disease pathogenesis and an exploration of novel drug targets, we propose that thrombin inhibition is an innovative tactic in the therapeutic battle against this devastating disease.

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“…Despite the role of oral anticoagulants as first-line medication in the prevention of ischemic stroke in patients with AF [ 39 ], it is still debatable whether the risk of AF-related dementia can be significantly reduced by oral anticoagulation treatment [ 40 , 41 ]. Recent data suggest that the novel anticoagulants would be a better choice for the prevention of dementia than warfarin (a vitamin K antagonist) [ 42 , 43 ], probably due to a lower rate of intracerebral bleeding [ 43 ]. Secondly, in terms of rhythm control strategies, cardioversion or AF ablation may result in sinus rhythm and improve cardiac output and cerebral perfusion.…”

Section: Psychosocial Consequences Of Afmentioning

confidence: 99%

Psychological aspects of atrial fibrillation: A systematic narrative review

et al. 2020

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Purpose of the review Atrial fibrillation (AF) is the most frequent arrhythmia in the general population. This review aims to provide a comprehensive overview of the psychological aspects of AF, compiling evidence from epidemiological, clinical, and basic research sources. Recent findings Findings from large-scale population-based and clinical longitudinal studies reveal an association between negative affectivity (e.g. depression) and the incidence and clinical prognosis of AF. Studies investigating the impact of work stress parameters on AF onset show conflicting results. Researchers have reported the impact of AF on cognitive decline and on health-related quality of life, and have highlighted the role of interoceptive cues in the development of AF symptom burden and gender differences in psychological covariates of AF. Among biological pathways linking psychosocial factors to AF, research on autonomic regulation has yielded the most evidence so far, showing that the onset of AF is associated with simultaneous sympatho-vagal activation rather than an increase in vagal or sympathetic drive alone. Thus, modulation of the autonomic nervous system is likely to be a promising strategy for protecting the myocardium from pro-arrhythmic autonomic influences. Summary In total, the findings show that AF is embedded as a disease condition in a psycho-societal context and is not an isolated medical problem per se. A broader perspective than a focus on the electrophysiology alone is urgently needed.

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Relationship of Anticoagulant Therapy With Cognitive Impairment Among Patients With Atrial Fibrillation: A Meta‐Analysis and Systematic Review

Abstract: OACs significantly reduce the occurrence of cognitive impairment in patients with AF. Compared with warfarin, new oral anticoagulants have an efficiently protective effect on cognition. In the range of INR 2-3, with the increase of TTR, the incidence of cognitive impairment is lower.

Cited by 57 publications

References 27 publications

Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials

Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials

Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer’s Disease

Psychological aspects of atrial fibrillation: A systematic narrative review

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