Atrial fibrillation and the risk of incident dementia: A meta-analysis

doi:10.1016/j.hrthm.2012.07.026

Heart Rhythm

Volume 9, Issue 11, November 2012, Pages 1761-1768.e2

https://doi.org/10.1016/j.hrthm.2012.07.026 Get rights and content

Background

The risk of cerebrovascular embolic events with atrial fibrillation (AF) is potentially linked to an increased risk of cognitive decline and dementia. However, epidemiologic studies exploring the association between AF and incident dementia have reported conflicting results.

Objective

The purpose of this study was to perform a meta-analysis of observational studies specifically designed to evaluate the prospective relationship between AF and incident dementia.

Methods

We searched PubMed, CENTRAL, BioMedCentral, Embase, Cardiosource, clinicaltrials.gov, and ISI Web of Science (January 1980 to May 2012). No language restriction was applied. Two independent reviewers screened titles and abstracts to identify population-based studies that prospectively evaluated the association between AF and the incidence of dementia in patients not suffering an acute stroke and with normal cognitive function at baseline, providing the hazard ratio (HR) obtained in multiple Cox regression analyses, and adjusted for all confounding variables. Two independent reviewers assessed risk of bias according to the Cochrane Collaboration, and extracted patient and study characteristics and the adjusted HR of incident dementia with its 95% confidence interval (CI) of patients with AF vs those without AF.

Results

Eight studies with 77,668 patients were included in the analysis. All studies had a prospective observational design and included elderly patients (mean age range 61–84 years) with normal cognitive function at baseline, of whom 11,700 (15%) had AF. After a mean follow-up of 7.7 ± 9.1 years (range 1.8–30 years), 4773 of 73,321 (6.5%) patients developed dementia. Two studies did not report the rates of dementia at follow-up but reported the adjusted HR and were included in the pooled analysis. At pooled analysis adjusted for baseline confounders and covariates, AF was independently associated with increased risk of incident dementia (HR = 1.42 [95% CI 1.17–1.72], P <.001).

Conclusion

AF is independently associated with increased risk of dementia. Patients with AF should be periodically screened for dementia, which should be included among the outcomes assessed in AF treatment trials.

Introduction

The prevalence of atrial fibrillation (AF) steadily increases with advancing age. Up to 10% of people aged 80 years or older suffer from this arrhythmia, and it is estimable that the number of elderly patients with AF will triple in the next 20 years.¹ The negative hemodynamic effects of AF resulting in reduced cardiac output and cerebral hypoperfusion,² and the risk of cerebrovascular micro- and macrothromboemboli,³ might predispose to the development of cognitive decline and dementia.

Similarly to AF, the prevalence of dementia rises with age,⁴ and the two conditions share similar background risk factors beyond age, including hypertension and diabetes. Recent data have suggested an association between AF and the risk of developing or worsening dementia, especially in patients after an acute stroke⁵ or in patients who already had evidence of cognitive impairment.⁶ Whether AF also increases the risk of dementia in patients with normal cognitive function not suffering an acute stroke, and independently from other potential confounders, is still controversial.7, 8, 9, 10, 11, 12, 13, 14, 15 To better evaluate the potential association between AF and the risk of dementia, we performed a meta-analysis of studies specifically designed to prospectively test the relationship between the presence of AF and the risk of incident dementia in patients with normal baseline cognitive function not suffering an acute stroke.

Section snippets

Data sources and selection

Two trained investigators (PS, LDB) independently searched major web databases from January 1980 to May 2012. Detailed description of the study search strategy is provided in the Appendix.

Study selection

Two independent reviewers (PS, LDB) performed study selection. Studies were included if (1) they had a prospective observational design, (2) they were specifically designed to test the relationship between the presence of AF and the risk of incident dementia, (3) they included patients with normal cognitive

Search results and study selection

The search permitted the retrieval of 2752 citations. We identified 18 observational studies, which were assessed according to compliance to the inclusion criteria. Seven studies prospectively assessed the relationship between presence of AF and incident dementia in patients suffering an acute stroke and thus did not meet the meta-analysis inclusion criteria (see Appendix). Two other studies were excluded either because it provided only unadjusted raw data for mental test scores without

Discussion

This systematic review, which enrolled more than 77,000 patients with normal baseline cognitive function and not suffering an acute stroke, showed that AF significantly increases the risk of developing dementia over follow-up, independently from other baseline confounders. Given the large number of subjects and the significant diversity among the subjects included, our analysis definitely provides additional information on the results of individual studies, with a greater ability to extrapolate

Conclusion

The results of our meta-analysis show that AF independently increases the risk of incident dementia in elderly patients without acute stroke and with normal baseline cognitive function. Patients with AF should be periodically screened for dementia, which should be included among the outcomes assessed in ongoing and future AF treatment trials. In particular, further studies are warranted to establish whether effective treatments of AF might reduce the risk of developing dementia.

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Cited by (218)

Impaired retinal micro-vascular function in patients with atrial fibrillation
2024, International Journal of Cardiology
Cardiovascular (CV) risk factors and CV diseases, in particular heart failure, are strongly associated with impaired microvascular retinal endothelial function. Whether atrial fibrillation (AF) contributes to vascular dysfunction is not clear. Therefore, the aim of this study was to investigate the impact of AF on retinal microvascular function.
In this study, vascular function was measured non-invasively with flicker-light induced vasodilatation of retinal arterioles (FIDart%). Patients with a history of AF and risk factors for heart failure (HF) or heart failure (n = 69; age 67.9 ± 9.2 years, 71% male, 35% HFrEF, 56% paroxysmal, 25% persistent, 19% permanent AF), as well as age, sex and ejection fraction matched patients with absent history of AF (n = 66; age 63.4 ± 10.6 years, 67% male, 47% HFrEF) were included. Patients with AF were further divided into those with paroxysmal AF (in sinus rhythm – AF_SR: n = 38, age 71.4 ± 9.2, 73% male), and those with AF at the time of the study visit.
Retinal microvascular function was impaired in patients with AF compared to patients without AF (FIDart% 1.1% [0.3–2.8] vs. 2.7% [1.3–5.1], p < 0.001). Patients currently in AF have poorer retinal microvascular function (FIDart% 0.8% [0.1–1.9) compared to patients with a history of AF but currently in SR at the time of retinal function measurement (1.5% [0.6–4.9] p = 0.017). In patients with AF, impaired retinal vascular function was independently associated with larger left atrial volume (mean 49.8 ± 18.4), even after correction for confounding factors in different models (SCR = -0. 251 to −0.256, p = 0.035–0.01).
AF in patients with heart failure is associated with impaired vascular function, even if currently in sinus rhythm. The association of retinal microvascular dysfunction with left atrial volume, a surrogate for elevated cardiac filling pressures, may further highlight the important interplay between the vasculature and elevated filling pressures in the development of AF.
Association of Atrial Fibrillation With Stroke and Dementia Accounting for Left Atrial Function and Size
2023, JACC: Advances
Atrial fibrillation (AF) is associated with higher risks of ischemic stroke (IS) and dementia. Whether alterations in left atrial (LA) function or size—atrial myopathy—confound these associations remains unknown.
The purpose of this study was to examine the association of prevalent and incident AF with ischemic stroke and dementia in the ARIC (Atherosclerosis Risk In Communities) study, adjusting for LA function and size.
Participants at visit 5 (2011-2013) with echocardiographic LA function (reservoir, conduit, contractile strain, and emptying fraction) and size (maximal, minimal volume index) data, and without prevalent stroke or dementia were followed through 2019. For analysis, we used time-varying Cox regression.
Among 5,458 participants (1,193 with AF, mean age of 76 years) in the stroke analysis and 5,461 participants (1,205 with AF, mean age of 75 years) in the dementia analysis, 209 participants developed ischemic stroke, and 773 developed dementia over 7.1 years (median). In a demographic and risk factor-adjusted model, AF was significantly associated with ischemic stroke (HR, 1.63; 95% CI: 1.11-2.37) and dementia (HR: 1.38, 95% CI: 1.13-1.70). After additionally adjusting for LA reservoir strain, these associations were attenuated and no longer statistically significant (stroke [HR: 1.33, 95% CI: 0.88-2.00], dementia [HR: 1.15, 95% CI: 0.92-1.43]). Associations with ischemic stroke and dementia were also attenuated and not statistically significant after adjustment for LA contractile strain, emptying fraction, and minimal volume index.
AF-ischemic stroke and AF-dementia associations were not statistically significant after adjusting for measures of atrial myopathy. This proof-of-concept analysis does not support AF as an independent risk factor for ischemic stroke and dementia.
Association of Left Atrial Structure and Function With Cognitive Function in Adults With Metabolic Syndrome
2022, American Journal of Cardiology
Atrial fibrillation has been associated with cognitive impairment. Whether subclinical abnormalities in atrial function and substrate predisposing to atrial fibrillation impact cognitive function has received limited attention. We tested associations of echocardiographic markers of atrial structure and function with cognitive function and decrease in 510 participants with obesity and metabolic syndrome (mean age SD of 64.4 [5.2] years in men and 66.5 [3.9] years in women). Left atrial (LA) markers (volume index, emptying fraction, strain, function index, and stiffness index) were estimated based on transthoracic echocardiography. General cognitive functioning (Mini-mental state examination), verbal ability (verbal fluency test), memory and attention (Digit Span Tests), and processing speed and executive function (Trail-Making Tests A and B) were assessed at baseline and at 2-year follow-up. Multiple linear regression was used to test associations of atrial markers (modeled in SD units) with baseline and 2-year changes in cognitive scores adjusted for demographic and health covariates. LA structure and function were not associated with cognitive function at baseline. Larger LA volume index (standardized β [95% confidence interval] −0.13 [−0.22 to −0.03]), lower peak longitudinal strain (−0.11 [−0.20 to −0.01]), and higher stiffness index (−0.18 [−0.28 to −0.08]) were associated with 2-year worsening in Trail-Making Test A. Strain measurements were also associated with a 2-year change in the Controlled Oral Word Association Test. In conclusion, overall, adverse markers of LA structure and function were associated with 2-year detrimental executive function-related cognitive changes in a sample of participants at high risk for cardiovascular disease, highlighting LA substrate as a potential risk factor for cognitive decrease and dementia.
Increase in Cerebral Blood Flow After Catheter Ablation of Atrial Fibrillation
2022, JACC: Clinical Electrophysiology
Recent studies have found that atrial fibrillation (AF) is a risk factor for cognitive impairment. Brain hypoperfusion is hypothesized as an underlying mechanism of cognitive decline in AF patients.
This study sought to assess changes in cerebral blood flow (CBF) and brain volume after catheter ablation of AF.
Patients undergoing catheter ablation of AF were enrolled in this prospective study. AF patients being treated with pharmaceuticals alone served as a control group. Brain magnetic resonance imaging was performed before and 6 months after catheter ablation. CBF was assessed by 2-dimensional phase-contrast magnetic resonance angiography. Brain volume and bilateral hippocampal volume were measured using FreeSurfer software.
Of the 57 study patients (age 64 ± 11 years; 45 men; paroxysmal AF: n = 22; nonparoxysmal AF: n = 35), 48 patients were freed from tachyarrhythmia recurrence beyond a 3-month blanking period. Changes in CBF and brain perfusion over 6 months were significantly greater in the study patients than control (CBF: 39.26 vs -34.86 mL; P = 0.01, ANCOVA; brain perfusion: 3.78 vs -3.02 mL/100 mL/min; P = 0.009, ANCOVA), while changes in total brain volume and bilateral hippocampal volume were similar between 2 groups (total brain volume: 2.57 vs -2.15 mL; P = 0.32, ANCOVA; bilateral hippocampal volume: 0.03 vs 0.04 mL; P = 0.8, ANCOVA). Nonparoxysmal AF at baseline was an independent predictor of an increase in CBF of >32.6 mL/min.
Catheter ablation of AF has favorable effects on CBF, particularly in nonparoxysmal AF. Our results may partially explain the association between cognitive decline and AF.
Socioeconomic disparities in use of rhythm control therapies in patients with incident atrial fibrillation: A Finnish nationwide cohort study
2022, IJC Heart and Vasculature
In patients with atrial fibrillation (AF), socioeconomic disparities have been reported in the use of oral anticoagulant therapy and outcomes, but whether income also affects the utilization of antiarrhythmic therapies (AATs) for rhythm control is unknown. We assessed the hypothesis that AF patients with higher income are more likely to receive AATs.
The nationwide retrospective registry based FinACAF cohort study covers all patients with AF from all levels of care in Finland. Patients were divided in AF diagnosis year and age-group specific income quintiles according to their highest annual income during 2004–2018. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription.
We identified 188 175 patients (mean age 72.6 ± 13.0 years; 49.6% female) with incident AF during 2010–2018. Patients in higher income quintiles had consistently higher use of all AAT modalities. When compared to patients in the lowest income quintile, the adjusted incidence rate ratios (95% CI) in the highest quintile were 1.53 (1.48–1.59) for any AAT, 1.71 (1.61–1.81) for AADs, 1.43 (1.37–1.49) for cardioversion, and 2.00 (1.76–2.27) for catheter ablation. No temporal change during study period was observed in the magnitude of income disparities in AAT use, except for a decrease in income-related differences in the use of AADs.
Profound income-related disparities exist in AAT use among patients with AF in Finland, especially in the use catheter ablation.
Exploring the association between regional fat distribution and atrial fibrillation risks: a comprehensive cohort study
2024, Frontiers in Endocrinology

View all citing articles on Scopus

: Drs. Santangeli and Di Biase both should be considered as first author. Dr. Natale has received consultant fees or honoraria from Biosense Webster, Boston Scientific, Medtronic, Biotronik, and LifeWatch. Dr. Di Biase has received consultant fees from Biosense Webster and Hansen Medical.

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ClinicalAtrial fibrillationAtrial fibrillation and the risk of incident dementia: A meta-analysis

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Data sources and selection

Study selection

Search results and study selection

Discussion

Conclusion

Am J Cardiol

J Am Coll Cardiol

Heart Rhythm

J Stroke Cerebrovasc Dis

Neurobiol Aging

Control Clin Trials

J Stroke Cerebrovasc Dis

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence

Circulation

Prevalence of dementia in the United States: the aging, demographics, and memory study

Neuroepidemiology

Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis

Neurology

Vascular factors predict rate of progression in Alzheimer disease

Neurology

Atrial fibrillation and risk of dementia: a prospective cohort study

J Am Geriatr Soc

Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment

Neurol Res

Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies

CMAJ

Clinical
Atrial fibrillation
Atrial fibrillation and the risk of incident dementia: A meta-analysis