Cognitive impairment associated with atrial fibrillation: a meta-analysis

Abstract

Background: Atrial fibrillation (AF) has been linked with an increased risk for cognitive impairment and dementia.

Purpose: To complete a meta-analysis of studies examining the association between AF and cognitive impairment.

Data sources: Search of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and hand search of article references.

Study selection: Prospective and nonprospective studies reporting adjusted risk estimates for the association between AF and cognitive impairment.

Data extraction: Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality.

Data synthesis: Twenty-one studies were included in the meta-analysis. Atrial fibrillation was significantly associated with a higher risk for cognitive impairment in patients with first-ever or recurrent stroke (relative risk [RR], 2.70 [95% CI, 1.82 to 4.00]) and in a broader population including patients with or without a history of stroke (RR, 1.40 [CI, 1.19 to 1.64]). The association in the latter group remained significant independent proof of clinical stroke history (RR, 1.34 [CI, 1.13 to 1.58]). However, there was significant heterogeneity among studies of the broader population (I2 = 69.4%). Limiting the analysis to prospective studies yielded similar results (RR, 1.36 [CI, 1.12 to 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P = 0.137) but did not alter the pooled estimate substantially (RR, 1.38 [CI, 1.22 to 1.56]).

Limitations: There is an inherent bias because of confounding variables in observational studies. There was significant heterogeneity among included studies.

Conclusion: Evidence suggests that AF is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the association between AF and subtypes of dementia as well as the cause of cognitive impairment.

Appendix Figure 1

Flow diagram of selection process.

Appendix Figure 2

Meta-analysis of the association between atrial fibrillation and Mini-Mental State Examination (MMSE) score ≤24 or MMSE decline≥ 3 points Studies are sorted by publication year. Diamond represents the pooled risk estimate. NR: not reported.

Appendix Figure 3

Funnel plot for assessment of publication bias among the 14 studies evaluating patients with or without history of stroke

Figure 1

Meta-analysis of 14 studies evaluating the association between atrial fibrillation and cognitive impairment in patients with or without history of stroke Studies are sorted by publication year. Diamond represents the pooled risk estimate. NR: not reported. * Patients with history of stroke were excluded in a subgroup analysis. † Patients with no focal neurologic deficits (i.e. previous strokes, head injuries, head neurosurgery, tumors of the central nervous system, and so forth) were only considered for this meta-analysis. ‡ Minimal adjustment should include at least adjustment for age. § History of stroke was included as a covariate in the multivariate adjusted model. ¶ Conversion from normal cognition to dementia. ║Conversion from mild cognitive impairment to dementia.

Figure 2

Separating dementia outcomes from cognitive impairment Studies are sorted by publication year. Diamond represents the pooled risk estimate. NR: not reported. * Patients with dementia were excluded.

Figure 3

The association between atrial fibrillation and cognitive impairment independent of stroke history Studies are sorted by publication year. Diamond represents the pooled risk estimate. NR: not reported. * Patients with history of stroke were excluded in a subgroup analysis. † Patients with no focal neurologic deficits (i.e. previous strokes, head injuries, head neurosurgery, tumors of the central nervous system, and so forth) were only considered for this meta-analysis. ‡ Minimal adjustment should include at least adjustment for age. § History of stroke was included as a covariate in the multivariate adjusted model.

Figure 4

Meta-analysis of 7 studies evaluating the association between atrial fibrillation and post-stroke cognitive impairment in patients with recurrent or first-ever stroke Studies are sorted by publication year. Diamond represents the pooled risk estimate. NR: not reported. * During the follow-up 5 additional patients developed atrial fibrillation (2 were diagnosed with post-stroke dementia)