Association between cognitive impairment and atrial fibrillation: A systematic review

doi:10.1053/jscd.2001.24663

Journal of Stroke and Cerebrovascular Diseases

Volume 10, Issue 2, March–April 2001, Pages 35-43

https://doi.org/10.1053/jscd.2001.24663 Get rights and content

Abstract

Purpose: Although it is well established that atrial fibrillation (AF) causes ischemic stroke, the relationship between AF and cognitive impairment is unclear. The aim of this systematic review is to investigate whether AF is associated with cognitive impairment or dementia. Materials and Methods: An electronic search of Medline, Embase, Psychlit, Cinahl and the Cochrane library was performed in March 2000 to identify studies in which the primary aim was to investigate the relationship between AF and cognitive impairment or dementia. Studies with relevant data on both cognitive function and AF (even if that was not the primary aim of the study) were also identified. Further references were identified from these sources. Results: Ten studies were identified, of which 4 were cross-sectional, 5 were case-control, and 1 was a prospective cohort study. The methodology and measures of cognition varied substantially, so it was not valid to apply formal meta-analysis techniques to the results. However, the methodology in all the studies was flawed in at least 1 aspect, including the reporting of results, external validity, and internal validity. Seven studies found an association between AF and at least 1 measure of cognition whereas 3 studies did not find an association. Conclusion: The evidence that AF is associated with cognitive impairment is inconclusive. Further studies are required to establish whether there is a relationship between AF and cognitive impairment, and if so, whether the relationship is causal. Copyright © 2001 by National Stroke Association

Section snippets

Materials and methods

Electronic searches of Medline (1966 to March 2000), Embase (1980 to March 2000), Psychlit (1887 to 1999), and the Cochrane library (see appendix for search strategy) were performed in April 2000. The abstract of each reference was read by one of the authors (G.E.M.), and the full reference was obtained if the abstract suggested that there would be data on AF and either cognitive impairment or dementia. Further references were identified from these sources. Inclusion criteria for this review

Results

We identified 10 studies that provided data on the relationship between AF and either cognitive impairment or dementia. They comprised 481 people with AF and 9,164 without AF (Table 1).The primary aim of the 7 studies was to investigate the relationship between AF and cognitive impairment.14, 15, 16, 17, 18, 19, 20 The primary aims of the other 3 studies were to investigate the relationship between subcortical infarction on computed tomography and AF,²¹ the relationship between 24-hour

Discussion

We identified only 10 studies that investigated the association between cognitive impairment or dementia and AF. Overall, there were approximately 20 times as many patients without AF than with AF, because there were a large number of people without AF recruited to the 4 community studies.19, 20, 22, 23, 24 Seven studies found an association between AF and cognitive impairment and 3 studies did not. Although the reporting of the studies was generally good (Table 2), at least 1 aspect of the

Acknowledgements

The authors thank the following colleagues for their invaluable help: Barbara Thomas (Cochrane Stroke Group) for advice about search strategies; Marshall Dozier (Erskine Medical Library) for searching Psychlit; Dr. Steff Lewis (medical statistician, Neurosciences Trials Unit) for her statistical advice; Dr. Susan Lewis (medical statistician, Geriatric Medicine University of Edinburgh) for calculating odds ratios for table 1; and Professor Archie Young for his helpful comments on the typescript.

References (25)

M Sudlow et al.
Prevalence of atrial fibrillation and eligibility for anticoagulants in the community
Lancet
(1998)
WH Frishman et al.
Twenty-four-hour ambulatory electrocardiography in elderly subjects: Prevalence of various arrhythmias and prognostic implications (report from the Bronx Longitudinal Aging Study)
Am Heart J
(1996)
MF Folstein et al.
Mini-mental state. A practical method for grading the cognitive state of patients for the clinician
J Psychiat Res
(1975)
PA Wolf et al.
Atrial fibrillation as an independent risk factor for stroke: The Framingham study
Stroke
(1991)
SMC Hardman et al.
Anticoagulation in heart disease
BMJ
(1999)
CB Upshaw
Hemodynamic changes after cardioversion of chronic atrial fibrillation
Arch Intern Med
(1998)
WM Feinberg et al.
Markers of thrombin and platelet activity in patients with atrial fibrillation: Correlation with stroke among 1531 participants in the stroke prevention in atrial fibrillation III study
Stroke
(1999)
P Peterson et al.
Silent cerebral infarction in chronic atrial fibrillation
Stroke
(1987)
M Guidotti et al.
Silent cerebral ischaemia in patients with chronic Atrial Fibrillation—A case-control study
Italian J Neurol Sci
(1990)
PA Kempster et al.
Asymptomatic cerebral infarction in patients with chronic atrial fibrillation
Stroke
(1988)

JC De Groot et al.

Cerebral white matter lesions and cognitive function: The Rotterdam Study

Ann Neurol

(2000)

LH Kuller et al.

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study

Stroke

(1998)

Cited by (37)

Vascular Dementia and Cognitive Impairment
2021, Stroke: Pathophysiology, Diagnosis, and Management
The increasing incidences of cognitive impairment and dementia are urgent public health issues, and cerebrovascular disease is emerging as a major contributor and attractive modifiable target for intervention. Vascular mild cognitive impairment (VaMCI) is a more recently recognized entity that includes mild cognitive deficits, while vascular dementia (VaD), as conventionally defined, is one of the most frequent forms of dementia. Further, when vascular contributions to other types of dementias are included, it is arguably the most common form of dementia. There are multiple neuroimaging methods to detect various markers of cerebrovascular disease, such as white matter lesions, perivascular spaces, and subclinical brain infarcts, all of which have been associated with worse cognitive function and decline. Emerging neuroimaging markers (e.g., blood-brain barrier integrity) and serum- or fluid-based biomarkers may help clinicians and researchers detect cerebrovascular disease-related cognitive dysfunction earlier in the disease course. Controlling cardiometabolic risk factors may help mitigate incidence of cerebrovascular disease and, in turn, reduce the risk of VaMCI and VaD. Future research is needed to identify the most salient targets for intervention.
The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation
2020, Canadian Journal of Cardiology
The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
Le programme de lignes directrices de la Société canadienne de cardiologie (SCC) en matière de fibrillation auriculaire (FA) a été élaboré pour aider les cliniciens à prendre en charge ces patients complexes, ainsi que pour orienter les décideurs politiques et les systèmes de soins de santé sur des questions connexes. La dernière édition complète des lignes directrices de la SCC en matière de FA a été publiée en 2010. Depuis lors, des mises à jour périodiques ont été publiées, traitant de domaines en évolution rapide. Cependant, en 2020, un grand nombre de développements s'y étaient ajoutés, couvrant un large éventail de domaines, ce qui a motivé le comité à créer une refonte complète des lignes directrices. L'édition 2020 des lignes directrices de la SCC en matière de FA représente un renouvellement complet qui intègre, met à jour et remplace les lignes directrices, les recommandations et les conseils pratiques des dix dernières années. Elle est destinée à être utilisée par les cliniciens praticiens de toutes les disciplines qui s'occupent de patients souffrant de FA. L'approche GRADE (Gradation des Recommandations, de l’Appréciation, du Développement et des Évaluations) a été utilisée pour évaluer la pertinence des recommandations et la qualité des résultats. Les domaines d'intérêt incluent : la classification et les définitions de la FA, son épidémiologie, sa physiopathologie, l’évaluation clinique, le dépistage de la FA, la détection et la gestion des facteurs de risque modifiables, l’approche intégrée de la gestion de la FA, la prévention des accidents vasculaires cérébraux, la gestion de l'arythmie, les différences entre les sexes et la FA dans des populations particulières. Des tableaux et figures ont été largement utilisés pour synthétiser les éléments importants et présenter les concepts clés. Ce document devrait représenter une aide importante pour l’intégration des connaissances et un outil pour aider à améliorer la gestion clinique de cette arythmie importante et difficile à traiter.
Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials
2019, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Cardiovascular disease is recognized as a risk factor for developing dementia or cognitive impairment, particularly atrial fibrillation (AF). A growing body of evidence suggests a relationship between AF and cognitive impairment ranging from mild to severe dementia (Kalantarian et al., 2013; Kwok et al., 2011; Mead and Keir, 2001; Santangeli et al., 2012; Stefanidis et al., 2018). It is worth noting that AF is associated with a five-fold increased risk of stroke and AF patients with a history of stroke are at a greater risk for an occurrence of dementia or cognitive impairment (January et al., 2014).
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], I² = 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], I² = 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.
Mechanisms, Clinical Significance, and Prevention of Cognitive Impairment in Patients With Atrial Fibrillation
2017, Canadian Journal of Cardiology
Citation Excerpt :
Most have reported a positive association in univariable and multivariable analyses. These studies have been the subject of 6 systematic reviews12,36-40 and 3 meta-analyses (Fig. 1).12,36,39 In fact, in all 3 meta-analyses, AF was independently associated with an increased risk of dementia (hazard ratios [HRs] ranging from 1.4 to 2.3) and cognitive decline (HRs ranging from 1.7 to 3.3).12,36,39
Atrial fibrillation (AF) and dementia are major health issues, with growing evidence suggesting a consistent association between AF and all forms of dementia. Although dementia and AF share several risk factors, the association appears to be independent of a history of clinical stroke and other comorbidities such as hypertension, heart failure, and diabetes. Proposed mechanisms linking AF to cognitive decline include altered hemodynamics resulting in cerebral hypoperfusion, inflammation, genetic factors, and silent cerebral ischemia due to subclinical microemboli. Evidence in support of the microembolization hypothesis includes the much higher incidence of silent cerebral ischemia detected in imaging studies in patients with AF, the association between presence of silent cerebral ischemia and cognitive dysfunction, and a “dose response” relationship between extent of silent cerebral ischemia and degree of cognitive impairment. Preventive therapies are currently being investigated and include anticoagulation, antiplatelet therapy, statins, pharmacological rhythm and rate control treatment strategies for AF, and catheter ablation procedures. Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) trial is currently assessing whether oral anticoagulation can prevent cognitive decline in patients at low risk of overt stroke. Considering the strong and independent association between AF and neurocognitive outcomes and the major clinical implications, evidence-based preventive approaches are critically required to diminish the health burden from the scourge of dementia and related conditions.
La fibrillation auriculaire (FA) et la démence sont des enjeux majeurs de santé pour lesquels de plus en plus d’évidences montrent un lien entre FA et toutes les formes de démence. Bien qu'ils partagent de nombreux facteurs de risques, l'association semble indépendante des antécédents d'accident vasculaire cérébral ou d'autres comorbidités comme l'hypertension, l'insuffisance cardiaque ou le diabète. Les mécanismes suspectés d'expliquer l'association entre FA et démence inclus l'hypoperfusion cérébrale, l'inflammation, les facteurs génétiques et l'ischémie cérébrale silencieuse. Parmi les données probantes supportant l'hypothèse micro-embolique, on note : une augmentation de la prévalence de l'ischémie cérébrale silencieuse sur les examens d'imagerie chez les patients en FA, une association entre ischémie cérébrale silencieuse et dysfonction cognitive, ainsi qu'une relation « dose-effet » entre le nombre de lésions d'ischémie cérébrale silencieuse et le degré d'atteinte cognitive. Les thérapies préventives qui sont actuellement explorées sont les suivantes : anticoagulation, thérapie antiplaquettaire, statines, contrôle du rythme pharmacologique ou par ablation par cathéter et contrôle de la fréquence cardiaque. L’étude BRAIN AF (Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation) évalue actuellement si une anticoagulation par voie orale peut prévenir le déclin cognitif chez les patients à faible risque d'accident vasculaire cérébral. Compte tenu de l'association forte et indépendantes qui existe entre FA et troubles cognitifs et les répercussions cliniques majeures, des approches préventives fondées sur des preuves.
Atrial fibrillation: A major risk factor for cognitive decline
2015, American Heart Journal
Citation Excerpt :
Numerous studies have been conducted examining the association between AF and cognitive impairment, with diverse populations ranging from case series of acute stroke inpatients to community-dwelling population-based longitudinal studies. Because of the heterogeneity of populations, methods, and analysis of the literature, 4 reviews4-7and 3 meta-analyses8-10 (Table I) were reviewed, whereas prospective cohort and cross-sectional studies were excluded. In general, studies support a positive association, with relative risk ranging from 1.4 to 2.8, depending on the presence of stroke.
Atrial fibrillation is a common disease of the elderly, conferring considerable morbidity and mortality related to cardiovascular effects and thromboembolic risks. Anticoagulation, antiarrhythmic medications, and rate control are the cornerstone of contemporary management, whereas ablation and evolving surgical techniques continue to play important secondary roles. Growing evidence shows that atrial fibrillation is also a risk factor for significant cognitive decline through a multitude of pathways, further contributing to morbidity and mortality. At the same time, cognitive decline associated with cryptogenic strokes may be the first clue to previously undiagnosed atrial fibrillation. These overlapping associations support the concept of cognitive screening and rhythm monitoring in these populations. New research suggests modulating effects of currently accepted treatments for atrial fibrillation on cognition; however, there remains the need for large multicenter studies to examine the effects of novel oral anticoagulants, rhythm and rate control, and left atrial appendage occlusion on long-term cognitive function.
Vascular Dementia and Cognitive Impairment
2015, Stroke: Pathophysiology, Diagnosis, and Management

View all citing articles on Scopus

^☆: Address reprint requests to Gillian E. Mead, MD, Department of Clinical and Surgical Sciences (Geriatric Medicine), The University of Edinburgh, 21 Chalmers St, Edinburgh EH3 9EW, UK.

View full text

Original ArticlesAssociation between cognitive impairment and atrial fibrillation: A systematic review☆

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Lancet

Am Heart J

J Psychiat Res

Atrial fibrillation as an independent risk factor for stroke: The Framingham study

Stroke

Anticoagulation in heart disease

BMJ

Hemodynamic changes after cardioversion of chronic atrial fibrillation

Arch Intern Med

Markers of thrombin and platelet activity in patients with atrial fibrillation: Correlation with stroke among 1531 participants in the stroke prevention in atrial fibrillation III study

Stroke

Silent cerebral infarction in chronic atrial fibrillation

Stroke

Silent cerebral ischaemia in patients with chronic Atrial Fibrillation—A case-control study

Italian J Neurol Sci

Asymptomatic cerebral infarction in patients with chronic atrial fibrillation

Stroke

Cerebral white matter lesions and cognitive function: The Rotterdam Study

Ann Neurol

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study

Stroke

Original Articles
Association between cognitive impairment and atrial fibrillation: A systematic review☆