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Dementia and Atrial Fibrillation: Pathophysiological Mechanisms and Therapeutic Implications

Spectrum of cerebral injuries from atrial fibrillation and atrial fibrillation management. (A) Large right middle cerebral artery territorial infarction on diffusion-weighted magnetic resonance imaging (MRI; arrow). (B) Ischemic infarction in multiple vascular territories on diffusion-weighted MRI. Left frontal lobe (blue arrow), right occipital lobe (red arrow), left occipital lobe (yellow arrow) are involved in this image on cerebral MRI (arrows). (C) Multiple microbleeds (white arrows) along with a larger right frontal subcortical hemorrhage (blue arrow) on brain MRI with susceptibility images. (D) Large high convexity right frontal hematoma with surrounding vasogenic edema on noncontrast computed tomography of the head (arrow).

Atrial fibrillation increases the risk of stroke by a factor of four- to fivefold, and dementia is a common consequence of stroke. However, atrial fibrillation has been associated with cognitive impairment and dementia, even in patients without prior overt stroke. Nonischemic mechanisms include cerebral hypoperfusion, vascular inflammation, brain atrophy, genetic factors, and shared risk factors such as age or hypertension. Critical appraisal of studies evaluating the association between atrial fibrillation and dementia in stroke-free patients reveals that several suffer from methodological issues, such as not including silent stroke or anticoagulation therapy in multivariate analyses. Some studies show a close relationship between atrial fibrillation and dementia due to silent stroke, in the absence of overt stroke. Evidence is accumulating that anticoagulation may be effective to decrease the risk of dementia in atrial fibrillation patients. Overall, the pathogenesis linking atrial fibrillation to dementia is likely multifactorial. Cerebral infarctions, including silent stroke, play a central role. These findings underscore the importance of stroke prevention measures in atrial fibrillation patients.

Dementia and atrial fibrillation have several epidemiologic characteristics in common, including high overall prevalence, increasing incidence with aging, and an expected rise in incidence.1, 2 Atrial fibrillation has been associated more closely with dementia3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 than other potentially comorbid age-related conditions.19, 20 However, while atrial fibrillation increases the risk of stroke by a factor of four- to fivefold,21 it is uncertain whether cognitive impairment in the context of atrial fibrillation is mediated by an increased risk of stroke or whether other factors are responsible. In this review, we critically appraise the evidence linking atrial fibrillation to dementia in patients with and without prior stroke of any type, summarize hypothesized pathophysiological mechanisms, and emphasize treatment strategies that target proposed mechanistic pathways.

Association of Atrial Fibrillation and Dementia

Patients with Prior Stroke

Ten percent of patients develop new-onset dementia after a first stroke, and more than one-third develop dementia after recurrent stroke.22 Different etiologies have been identified for poststroke dementia, including extensive or multiple infarcts, infarcts disrupting cognitively sensitive circuits, or the presence of concomitant severe small-vessel disease23 (Figures 1 and 2).

The association between atrial fibrillation-related stroke and dementia is well recognized.24, 25 A meta-analysis of 7 studies showed that atrial fibrillation was associated with a more than twofold increase in the risk of developing poststroke dementia.24

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-Romain Chopard, MD, Gregory Piazza, MD, Seth Alan Gale, MD, Umberto Campia, MD, Ida Ehlers Albertsen, MD, Jisoo Kim, MD, Samuel Z. Goldhaber, MD

This article originally appeared in the December issue of The American Journal of Medicine.

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