Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cognitive dysfunction in atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in adults, and its incidence and prevalence increase with age. The risk of cognitive impairment and dementia also increases with age, and both AF and cognitive impairment or dementia share important risk factors. In meta-analyses of published studies, AF is associated with a 2.4-fold and 1.4-fold increase in the risk of dementia in patients with or without a history of stroke, respectively. This association is independent of shared risk factors such as hypertension and diabetes mellitus. Neuroimaging has illustrated several potential mechanisms of cognitive decline in patients with AF. AF is associated with increased prevalence of silent cerebral infarcts, and more recent data also suggest an increased prevalence of cerebral microbleeds with AF. AF is also associated with a pro-inflammatory state, and the relationship between AF-induced systemic inflammation and dementia remains to be investigated. Preliminary reports indicate that anticoagulation medication including warfarin can reduce the risk of cognitive impairment in patients with AF. Catheter ablation, increasingly used to maintain sinus rhythm in patients with AF, is associated with the formation of new silent cerebral lesions. The majority of these lesions are not detectable after 1 year, and insufficient data are available to evaluate their effect on cognition. Large prospective studies are urgently needed to confirm the association between AF and dementia, to elucidate the associated mechanisms, and to investigate the effect of anticoagulation and rhythm control on cognition.

Key points

  • Atrial fibrillation is associated with increased risks of dementia and cognitive impairment, independent of history of stroke and other shared risk factors.

  • Proposed mechanisms of cognitive impairment in atrial fibrillation include cerebral thromboembolism, cerebral hypoperfusion, and cerebral microbleeds.

  • Anticoagulation might be protective against cognitive impairment in atrial fibrillation, but further prospective studies are needed.

  • Catheter ablation of atrial fibrillation is associated with new silent cerebral lesions, but the effect on cognitive function is unknown.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Proposed pathophysiology of cognitive impairment in atrial fibrillation.
Fig. 2: Neuroimaging findings in patients with atrial fibrillation.
Fig. 3: Interaction between atrial fibrillation, cerebral infarction, and mild cognitive impairment.
Fig. 4: Potential effects of treatment for atrial fibrillation on the risk of future dementia.
Fig. 5: Proposed aetiology of silent cerebral lesions after catheter ablation of atrial fibrillation.

Similar content being viewed by others

References

  1. Miyasaka, Y. et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 114, 119–125 (2006).

    PubMed  Google Scholar 

  2. Chugh, S. S. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129, 837–847 (2014).

    PubMed  Google Scholar 

  3. Go, A. S. et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285, 2370–2375 (2001).

    CAS  PubMed  Google Scholar 

  4. Hebert, L. E., Weuve, J., Scherr, P. A. & Evans, D. A. Alzheimer disease in the United States estimated using the 2010 census. Neurology 80, 1778–1783 (2013).

    PubMed  PubMed Central  Google Scholar 

  5. Wimo, A., Jonsson, L. & Winblad, B. An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dement. Geriatr. Cogn. Disord. 21, 175–181 (2006).

    CAS  PubMed  Google Scholar 

  6. Wimo, A., Winblad, B. & Jonsson, L. An estimate of the total worldwide societal costs of dementia in 2005. Alzheimers Dement. 3, 81–91 (2007).

    PubMed  Google Scholar 

  7. Benjamin, E. J. et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 271, 840–844 (1994).

    CAS  PubMed  Google Scholar 

  8. Bohm, M. et al. Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk. Hypertension 65, 651–661 (2015).

    PubMed  Google Scholar 

  9. Gudala, K., Bansal, D., Schifano, F. & Bhansali, A. Diabetes mellitus and risk of dementia: A meta-analysis of prospective observational studies. J. Diabetes Investig. 4, 640–650 (2013).

    PubMed  PubMed Central  Google Scholar 

  10. Pendlebury, S. T. & Rothwell, P. M. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 8, 1006–1018 (2009).

    PubMed  Google Scholar 

  11. Wolf, P. A., Abbott, R. D. & Kannel, W. B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22, 983–988 (1991).

    CAS  PubMed  Google Scholar 

  12. Alosco, M. L. et al. Atrial fibrillation exacerbates cognitive dysfunction and cerebral perfusion in heart failure. Pacing Clin. Electrophysiol. 38, 178–186 (2015).

    PubMed  Google Scholar 

  13. Graff-Radford, J. et al. Atrial fibrillation, cognitive impairment, and neuroimaging. Alzheimers Dement. 12, 391–398 (2016).

    PubMed  Google Scholar 

  14. Cherubini, A. et al. Underrecognition and undertreatment of dementia in Italian nursing homes. J. Am. Med. Dir. Assoc. 13, 759.e7–759.e13 (2012).

    Google Scholar 

  15. Connolly, A., Gaehl, E., Martin, H., Morris, J. & Purandare, N. Underdiagnosis of dementia in primary care: variations in the observed prevalence and comparisons to the expected prevalence. Aging Ment. Health 15, 978–984 (2011).

    PubMed  Google Scholar 

  16. Erkinjuntti, T., Ostbye, T., Steenhuis, R. & Hachinski, V. The effect of different diagnostic criteria on the prevalence of dementia. N. Engl. J. Med. 337, 1667–1674 (1997).

    CAS  PubMed  Google Scholar 

  17. Engdahl, J., Andersson, L., Mirskaya, M. & Rosenqvist, M. Stepwise screening of atrial fibrillation in a 75-year-old population: implications for stroke prevention. Circulation 127, 930–937 (2013).

    PubMed  Google Scholar 

  18. Lin, H. J. et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 27, 1760–1764 (1996).

    CAS  PubMed  Google Scholar 

  19. Marini, C. et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke 36, 1115–1119 (2005).

    PubMed  Google Scholar 

  20. Barba, R. et al. Poststroke dementia: clinical features and risk factors. Stroke 31, 1494–1501 (2000).

    CAS  PubMed  Google Scholar 

  21. Censori, B. et al. Dementia after first stroke. Stroke 27, 1205–1210 (1996).

    CAS  PubMed  Google Scholar 

  22. Inzitari, D. et al. Incidence and determinants of poststroke dementia as defined by an informant interview method in a hospital-based stroke registry. Stroke 29, 2087–2093 (1998).

    CAS  PubMed  Google Scholar 

  23. Zhou, D. H. et al. Study on frequency and predictors of dementia after ischemic stroke: the Chongqing stroke study. J. Neurol. 251, 421–427 (2004).

    PubMed  Google Scholar 

  24. Kwok, C. S., Loke, Y. K., Hale, R., Potter, J. F. & Myint, P. K. Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis. Neurology 76, 914–922 (2011).

    CAS  PubMed  Google Scholar 

  25. Lees, R. A. et al. Cognitive assessment in stroke: feasibility and test properties using differing approaches to scoring of incomplete items. Int. J. Geriatr. Psychiatry 32, 1072–1078 (2017).

    PubMed  Google Scholar 

  26. Bunch, T. J. et al. Atrial fibrillation is independently associated with senile, vascular, and Alzheimer’s dementia. Heart Rhythm 7, 433–437 (2010).

    PubMed  Google Scholar 

  27. Ott, A. et al. Atrial fibrillation and dementia in a population-based study. The Rotterdam Study. Stroke 28, 316–321 (1997).

    CAS  PubMed  Google Scholar 

  28. Marengoni, A., Qiu, C., Winblad, B. & Fratiglioni, L. Atrial fibrillation, stroke and dementia in the very old: a population-based study. Neurobiol. Aging 32, 1336–1337 (2011).

    PubMed  Google Scholar 

  29. Haring, B. et al. Cardiovascular disease and cognitive decline in postmenopausal women: results from the Women’s Health Initiative Memory study. J. Am. Heart Assoc. 2, e000369 (2013).

    PubMed  PubMed Central  Google Scholar 

  30. Peters, R. et al. Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial. J. Hypertens. 27, 2055–2062 (2009).

    CAS  PubMed  Google Scholar 

  31. Marzona, I. et al. Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies. CMAJ 184, E329–E336 (2012).

    PubMed  PubMed Central  Google Scholar 

  32. Kalantarian, S. et al. Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis. Ann. Intern. Med. 161, 650–658 (2014).

    PubMed  PubMed Central  Google Scholar 

  33. Santangeli, P. et al. Atrial fibrillation and the risk of incident dementia: a meta-analysis. Heart Rhythm 9, 1761–1768 (2012).

    PubMed  Google Scholar 

  34. de Bruijn, R. F. et al. Association between atrial fibrillation and dementia in the general population. JAMA Neurol. 72, 1288–1294 (2015).

    PubMed  Google Scholar 

  35. Petersen, R. C. et al. Mild cognitive impairment: ten years later. Arch. Neurol. 66, 1447–1455 (2009).

    PubMed  PubMed Central  Google Scholar 

  36. Forti, P. et al. Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI). Arch. Gerontol. Geriatr. 44 (Suppl. 1), 155–165 (2007).

    PubMed  Google Scholar 

  37. Di Carlo, A. et al. CIND and MCI in the Italian elderly: frequency, vascular risk factors, progression to dementia. Neurology 68, 1909–1916 (2007).

    PubMed  Google Scholar 

  38. Thacker, E. L. et al. Atrial fibrillation and cognitive decline: a longitudinal cohort study. Neurology 81, 119–125 (2013).

    PubMed  PubMed Central  Google Scholar 

  39. Tilvis, R. S. et al. Predictors of cognitive decline and mortality of aged people over a 10-year period. J. Gerontol. A. 59, 268–274 (2004).

    Google Scholar 

  40. Healey, J. S. et al. Subclinical atrial fibrillation and the risk of stroke. N. Eng. J. Med. 366, 120–129 (2012).

    CAS  Google Scholar 

  41. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01938248 (2018).

  42. Ezekowitz, M. D. et al. Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The veterans affairs stroke prevention nonrheumatic atrial fibrillation investigators. Circulation 92, 2178–2182 (1995).

    CAS  PubMed  Google Scholar 

  43. Wardlaw, J. M. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12, 822–838 (2013).

    PubMed  PubMed Central  Google Scholar 

  44. Vermeer, S. E. et al. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 34, 1126–1129 (2003).

    PubMed  Google Scholar 

  45. Vermeer, S. E. et al. Silent brain infarcts and the risk of dementia and cognitive decline. N. Engl. J. Med. 348, 1215–1222 (2003).

    PubMed  Google Scholar 

  46. Cha, M. J. et al. Prevalence of and risk factors for silent ischemic stroke in patients with atrial fibrillation as determined by brain magnetic resonance imaging. Am. J. Cardiol. 113, 655–661 (2014).

    PubMed  Google Scholar 

  47. Chen, L. Y. et al. Atrial fibrillation and cognitive decline-the role of subclinical cerebral infarcts: the atherosclerosis risk in communities study. Stroke 45, 2568–2574 (2014).

    PubMed  PubMed Central  Google Scholar 

  48. Das, R. R. et al. Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke 39, 2929–2935 (2008).

    PubMed  PubMed Central  Google Scholar 

  49. Gaita, F. et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J. Am. Coll. Cardiol. 62, 1990–1997 (2013).

    PubMed  Google Scholar 

  50. Kobayashi, A., Iguchi, M., Shimizu, S. & Uchiyama, S. Silent cerebral infarcts and cerebral white matter lesions in patients with nonvalvular atrial fibrillation. J. Stroke Cerebrovasc. Dis. 21, 310–317 (2012).

    PubMed  Google Scholar 

  51. Longstreth, W. T. Jr et al. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 33, 2376–2382 (2002).

    PubMed  Google Scholar 

  52. Marfella, R. et al. Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients. J. Am. Coll. Cardiol. 62, 525–530 (2013).

    PubMed  Google Scholar 

  53. Knecht, S. et al. Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy. Eur. Heart J. 29, 2125–2132 (2008).

    PubMed  Google Scholar 

  54. Greenberg, S. M. et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 8, 165–174 (2009).

    PubMed  PubMed Central  Google Scholar 

  55. Lovelock, C. E. et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke 41, 1222–1228 (2010).

    CAS  PubMed  Google Scholar 

  56. Poels, M. M. et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology 78, 326–333 (2012).

    CAS  PubMed  Google Scholar 

  57. van Etten, E. S. et al. Incidence of symptomatic hemorrhage in patients with lobar microbleeds. Stroke 45, 2280–2285 (2014).

    PubMed  PubMed Central  Google Scholar 

  58. Akoudad, S. et al. Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol. 73, 934–943 (2016).

    PubMed  PubMed Central  Google Scholar 

  59. Charidimou, A., Kakar, P., Fox, Z. & Werring, D. J. Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 44, 995–1001 (2013).

    PubMed  Google Scholar 

  60. Haji, S. et al. The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation. J. Neurol. 263, 238–244 (2016).

    CAS  PubMed  Google Scholar 

  61. Song, T. J. et al. Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation. Neurology 83, 1308–1315 (2014).

    PubMed  Google Scholar 

  62. Song, T. J. et al. The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation. Eur. J. Neurol. 20, 502–508 (2013).

    PubMed  Google Scholar 

  63. Georgiadis, D. et al. Intracranial microembolic signals in 500 patients with potential cardiac or carotid embolic source and in normal controls. Stroke 28, 1203–1207 (1997).

    CAS  PubMed  Google Scholar 

  64. Haeusler, K. G., Wilson, D., Fiebach, J. B., Kirchhof, P. & Werring, D. J. Brain MRI to personalise atrial fibrillation therapy: current evidence and perspectives. Heart 100, 1408–1413 (2014).

    PubMed  Google Scholar 

  65. Tsao, C. W. et al. Association of arterial stiffness with progression of subclinical brain and cognitive disease. Neurology 86, 619–626 (2016).

    PubMed  PubMed Central  Google Scholar 

  66. Jefferson, A. L. et al. Lower cardiac index levels relate to lower cerebral blood flow in older adults. Neurology 89, 2327–2334 (2017).

    PubMed  PubMed Central  Google Scholar 

  67. Jefferson, A. L. et al. Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study). Am. J. Cardiol. 108, 1346–1351 (2011).

    PubMed  PubMed Central  Google Scholar 

  68. Iguchi, Y. et al. Prevalence of atrial fibrillation in community-dwelling Japanese aged 40 years or older in Japan: analysis of 41,436 non-employee residents in Kurashiki-city. Circ. J. 72, 909–913 (2008).

    PubMed  Google Scholar 

  69. Qiu, C. et al. Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Arch. Intern. Med. 166, 1003–1008 (2006).

    PubMed  Google Scholar 

  70. Roberts, R. O. et al. Cardiac disease associated with increased risk of nonamnestic cognitive impairment: stronger effect on women. JAMA Neurol. 70, 374–382 (2013).

    PubMed  PubMed Central  Google Scholar 

  71. Tremblay-Gravel, M. et al. Blood pressure and atrial fibrillation: a combined AF-CHF and AFFIRM analysis. J. Cardiovasc. Electrophysiol. 26, 509–514 (2015).

    PubMed  Google Scholar 

  72. Hailpern, S. M., Melamed, M. L., Cohen, H. W. & Hostetter, T. H. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J. Am. Soc. Nephrol. 18, 2205–2213 (2007).

    PubMed  Google Scholar 

  73. Liao, J. N. et al. Incidence and risk factors for new-onset atrial fibrillation among patients with end-stage renal disease undergoing renal replacement therapy. Kidney Int. 87, 1209–1215 (2015).

    PubMed  Google Scholar 

  74. Mukamal, K. J. et al. Prospective study of alcohol consumption and risk of dementia in older adults. JAMA 289, 1405–1413 (2003).

    CAS  PubMed  Google Scholar 

  75. Mukamal, K. J., Tolstrup, J. S., Friberg, J., Jensen, G. & Gronbaek, M. Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study. Circulation 112, 1736–1742 (2005).

    PubMed  Google Scholar 

  76. Gami, A. S. et al. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J. Am. Coll. Cardiol. 49, 565–571 (2007).

    PubMed  Google Scholar 

  77. Spira, A. P. et al. Sleep-disordered breathing and cognition in older women. J. Am. Geriatr. Soc. 56, 45–50 (2008).

    PubMed  Google Scholar 

  78. Hu, Y. F., Chen, Y. J., Lin, Y. J. & Chen, S. A. Inflammation and the pathogenesis of atrial fibrillation. Nat. Rev. Cardiol. 12, 230–243 (2015).

    CAS  PubMed  Google Scholar 

  79. Barber, M. et al. Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation. J. Thromb. Haemost. 2, 1873–1878 (2004).

    CAS  PubMed  Google Scholar 

  80. Austin, B. P. et al. Effects of hypoperfusion in Alzheimer’s disease. J. Alzheimers Dis. 26 (Suppl. 3), 123–133 (2011).

    PubMed  PubMed Central  Google Scholar 

  81. de Bruijn, R. F. et al. Subclinical cardiac dysfunction increases the risk of stroke and dementia: the Rotterdam Study. Neurology 84, 833–840 (2015).

    PubMed  Google Scholar 

  82. Lavy, S. et al. Effect of chronic atrial fibrillation on regional cerebral blood flow. Stroke 11, 35–38 (1980).

    CAS  PubMed  Google Scholar 

  83. Gardarsdottir, M. et al. Atrial fibrillation is associated with decreased total cerebral blood flow and brain perfusion. Europace 20, 1252–1258 (2017).

    PubMed Central  Google Scholar 

  84. Shi, Y. et al. Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. J. Cereb. Blood Flow Metab. 36, 1653–1667 (2016).

    PubMed  PubMed Central  Google Scholar 

  85. Charidimou, A., Shakeshaft, C. & Werring, D. J. Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front. Neurol. 3, 133 (2012).

    PubMed  PubMed Central  Google Scholar 

  86. Benedictus, M. R. et al. Prognostic factors for cognitive decline after intracerebral hemorrhage. Stroke 46, 2773–2778 (2015).

    CAS  PubMed  Google Scholar 

  87. Garcia, P. Y. et al. Cognitive impairment and dementia after intracerebral hemorrhage: a cross-sectional study of a hospital-based series. J. Stroke Cerebrovasc. Dis. 22, 80–86 (2013).

    PubMed  Google Scholar 

  88. Horstmann, S. et al. Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur. J. Neurol. 22, 1355–1362 (2015).

    CAS  PubMed  Google Scholar 

  89. Orken, D. N. et al. New cerebral microbleeds in ischemic stroke patients on warfarin treatment: two-year follow-up. Clin. Neurol. Neurosurg. 115, 1682–1685 (2013).

    PubMed  Google Scholar 

  90. Lei, C. et al. Association between cerebral microbleeds and cognitive function: a systematic review. J. Neurol. Neurosurg. Psychiatry 84, 693–697 (2013).

    PubMed  Google Scholar 

  91. Selim, M. & Diener, H. C. Atrial fibrillation and microbleeds. Stroke 48, 2660–2664 (2017).

    PubMed  Google Scholar 

  92. Chao, T. F. et al. Plasma asymmetric dimethylarginine and adverse events in patients with atrial fibrillation referred for coronary angiogram. PLoS ONE 8, e71675 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Conway, D. S., Pearce, L. A., Chin, B. S., Hart, R. G. & Lip, G. Y. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 107, 3141–3145 (2003).

    CAS  PubMed  Google Scholar 

  94. Lip, G. Y., Patel, J. V., Hughes, E. & Hart, R. G. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke 38, 1229–1237 (2007).

    CAS  PubMed  Google Scholar 

  95. Roldan, V. et al. High sensitivity cardiac troponin T and interleukin-6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation. J. Thromb. Haemost. 10, 1500–1507 (2012).

    CAS  PubMed  Google Scholar 

  96. Enciu, A. M. & Popescu, B. O. Is there a causal link between inflammation and dementia? Biomed. Res. Int. 2013, 316495 (2013).

    PubMed  PubMed Central  Google Scholar 

  97. Sidorova, T. N. et al. Reactive γ-ketoaldehydes promote protein misfolding and preamyloid oligomer formation in rapidly-activated atrial cells. J. Mol. Cell. Cardiol. 79, 295–302 (2015).

    CAS  PubMed  Google Scholar 

  98. Boutaud, O., Montine, T. J., Chang, L., Klein, W. L. & Oates, J. A. PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42. J. Neurochem. 96, 917–923 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. January, C. T. et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130, e199–e267 (2014).

    PubMed  PubMed Central  Google Scholar 

  100. Jacobs, V., Graves, K. G. & Bunch, T. J. Anticoagulant use in atrial fibrillation and risk of dementia: review of contemporary knowledge. Expert Rev. Cardiovasc. Ther. 15, 897–903 (2017).

    CAS  PubMed  Google Scholar 

  101. Madhavan, M. et al. Efficacy of warfarin anticoagulation and incident dementia in a community based cohort of atrial fibrillation. Mayo Clin. Proc. 93, 145–154 (2018).

    CAS  PubMed  Google Scholar 

  102. Mavaddat, N. et al. Warfarin versus aspirin for prevention of cognitive decline in atrial fibrillation: randomized controlled trial (Birmingham Atrial Fibrillation Treatment of the Aged Study). Stroke 45, 1381–1386 (2014).

    CAS  PubMed  Google Scholar 

  103. Moffitt, P., Lane, D. A., Park, H., O’Connell, J. & Quinn, T. J. Thromboprophylaxis in atrial fibrillation and association with cognitive decline: systematic review. Age Ageing 45, 767–775 (2016).

    PubMed  Google Scholar 

  104. Flaker, G. C. et al. Cognitive function and anticoagulation control in patients with atrial fibrillation. Circ. Cardiovasc. Qual. Outcomes 3, 277–283 (2010).

    PubMed  Google Scholar 

  105. Jacobs, V. et al. Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia. Heart Rhythm 11, 2206–2213 (2014).

    PubMed  Google Scholar 

  106. Jacobs, V. et al. Percent time with a supratherapeutic INR in atrial fibrillation patients also using an antiplatelet agent is associated with long-term risk of dementia. J. Cardiovasc. Electrophysiol. 26, 1180–1186 (2015).

    PubMed  Google Scholar 

  107. Reynolds, M. W. et al. Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis. Chest 126, 1938–1945 (2004).

    PubMed  Google Scholar 

  108. O’ Donnell, M. J. et al. Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study. Am. Heart J. 178, 145–150 (2016).

    Google Scholar 

  109. Granger, C. B. et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365, 981–992 (2011).

    CAS  PubMed  Google Scholar 

  110. Connolly, S. J. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361, 1139–1151 (2009).

    CAS  PubMed  Google Scholar 

  111. Patel, M. R. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365, 883–891 (2011).

    CAS  PubMed  Google Scholar 

  112. Jacobs, V. et al. Long-term population-based cerebral ischemic event and cognitive outcomes of direct oral anticoagulants compared with warfarin among long-term anticoagulated patients for atrial fibrillation. Am. J. Cardiol. 118, 210–214 (2016).

    PubMed  Google Scholar 

  113. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02387229 (2018).

  114. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01994265 (2017).

  115. Reddy, V. Y. et al. 5-Year outcomes after left atrial appendage closure: from the PREVAIL and PROTECT AF trials. J. Am. Coll. Cardiol. 70, 2964–2975 (2017).

    PubMed  Google Scholar 

  116. Van Gelder, I. C. et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N. Engl. J. Med. 347, 1834–1840 (2002).

    PubMed  Google Scholar 

  117. Chung, M. K. et al. Functional status in rate- versus rhythm-control strategies for atrial fibrillation: results of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Functional Status Substudy. J. Am. Coll. Cardiol. 46, 1891–1899 (2005).

    PubMed  Google Scholar 

  118. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01288352 (2017).

  119. Cappato, R. et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ. Arrhythm. Electrophysiol. 3, 32–38 (2010).

    PubMed  Google Scholar 

  120. Deneke, T. et al. Postablation asymptomatic cerebral lesions: long-term follow-up using magnetic resonance imaging. Heart Rhythm 8, 1705–1711 (2011).

    PubMed  Google Scholar 

  121. Gaita, F. et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J. Cardiovasc. Electrophysiol. 22, 961–968 (2011).

    PubMed  Google Scholar 

  122. Gaita, F. et al. Radiofrequency catheter ablation of atrial fibrillation: a cause of silent thromboembolism? Magnetic resonance imaging assessment of cerebral thromboembolism in patients undergoing ablation of atrial fibrillation. Circulation 122, 1667–1673 (2010).

    PubMed  Google Scholar 

  123. Herrera Siklody, C. et al. Incidence of asymptomatic intracranial embolic events after pulmonary vein isolation: comparison of different atrial fibrillation ablation technologies in a multicenter study. J. Am. Coll. Cardiol. 58, 681–688 (2011).

    PubMed  Google Scholar 

  124. Martinek, M. et al. Asymptomatic cerebral lesions during pulmonary vein isolation under uninterrupted oral anticoagulation. Europace 15, 325–331 (2013).

    PubMed  Google Scholar 

  125. Scaglione, M. et al. Impact of ablation catheter irrigation design on silent cerebral embolism after radiofrequency catheter ablation of atrial fibrillation: results from a pilot study. J. Cardiovasc. Electrophysiol. 23, 801–805 (2012).

    PubMed  Google Scholar 

  126. Neumann, T. et al. MEDAFI-Trial (micro-embolization during ablation of atrial fibrillation): comparison of pulmonary vein isolation using cryoballoon technique versus radiofrequency energy. Europace 13, 37–44 (2011).

    PubMed  Google Scholar 

  127. Di Biase, L. et al. Does periprocedural anticoagulation management of atrial fibrillation affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging in patients undergoing radiofrequency atrial fibrillation ablation with open irrigated catheters? Results from a prospective multicenter study. Heart Rhythm 11, 791–798 (2014).

    PubMed  Google Scholar 

  128. Zhao, Y. et al. New oral anticoagulants compared to warfarin for perioperative anticoagulation in patients undergoing atrial fibrillation catheter ablation: a meta-analysis of continuous or interrupted new oral anticoagulants during ablation compared to interrupted or continuous warfarin. J. Interv. Card. Electrophysiol. 48, 267–282 (2017).

    PubMed  Google Scholar 

  129. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02227550 (2017).

  130. Ichiki, H. et al. Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram. J. Cardiovasc. Electrophysiol. 23, 567–573 (2012).

    PubMed  Google Scholar 

  131. Madhavan, M., Govil, S. R. & Asirvatham, S. J. Signals. Circ. Arrhythm. Electrophysiol. 5, 2–4 (2012).

    PubMed  Google Scholar 

  132. Nakamura, K. et al. Silent cerebral ischemic lesions after catheter ablation of atrial fibrillation in patients on 5 types of periprocedural oral anticoagulation-predictors of diffusion-weighted imaging-positive lesions and follow-up magnetic resonance imaging. Circ. J. 80, 870–877 (2016).

    CAS  PubMed  Google Scholar 

  133. Rillig, A. et al. Incidence and long-term follow-up of silent cerebral lesions after pulmonary vein isolation using a remote robotic navigation sytem as compared to manual ablation. Circ. Arrhythm Electrophysiol. 5, 15–21 (2012).

    PubMed  Google Scholar 

  134. Haines, D. E. et al. Microembolism and catheter ablation II: effects of cerebral microemboli injection in a canine model. Circ. Arrhythm. Electrophysiol. 6, 23–30 (2013).

    PubMed  Google Scholar 

  135. Medi, C. et al. Subtle post-procedural cognitive dysfunction after atrial fibrillation ablation. J. Am. Coll. Cardiol. 62, 531–539 (2013).

    PubMed  Google Scholar 

  136. von Bary, C. et al. Silent cerebral events as a result of left atrial catheter ablation do not cause neuropsychological sequelae — a MRI-controlled multicenter study. J. Interv. Card. Electrophysiol. 43, 217–226 (2015).

    Google Scholar 

  137. Kokmen, E., Whisnant, J. P., O’Fallon, W. M., Chu, C. P. & Beard, C. M. Dementia after ischemic stroke: a population-based study in Rochester, Minnesota (1960–1984). Neurology 46, 154–159 (1996).

    CAS  PubMed  Google Scholar 

  138. Bunch, T. J. et al. Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score. Heart Rhythm 10, 1272–1277 (2013).

    PubMed  Google Scholar 

  139. van Veluw, S. J. et al. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 16, 730–740 (2017).

    PubMed  PubMed Central  Google Scholar 

  140. van Kuilenburg, J. et al. Persisting thrombin activity in elderly patients with atrial fibrillation on oral anticoagulation is decreased by anti-inflammatory therapy with intensive cholesterol-lowering treatment. J. Clin. Lipidol. 5, 273–280 (2011).

    PubMed  Google Scholar 

  141. Lappegard, K. T. et al. Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy. J. Neuroinflamm. 10, 78 (2013).

    Google Scholar 

  142. Dublin, S. et al. Atrial fibrillation and risk of dementia: a prospective cohort study. J. Am. Geriatr. Soc. 59, 1369–1375 (2011).

    PubMed  PubMed Central  Google Scholar 

  143. Elias, M. F. et al. Atrial fibrillation is associated with lower cognitive performance in the Framingham offspring men. J. Stroke Cerebrovasc. Dis. 15, 214–222 (2006).

    PubMed  Google Scholar 

  144. Park, H., Hildreth, A., Thomson, R. & O’Connell, J. Non-valvular atrial fibrillation and cognitive decline: a longitudinal cohort study. Age Ageing 36, 157–163 (2007).

    PubMed  Google Scholar 

  145. Rastas, S. et al. Atrial fibrillation, stroke, and cognition: a longitudinal population-based study of people aged 85 and older. Stroke 38, 1454–1460 (2007).

    PubMed  Google Scholar 

  146. Li, J. et al. Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology 76, 1485–1491 (2011).

    CAS  PubMed  Google Scholar 

  147. Jozwiak, A., Guzik, P., Mathew, A., Wykretowicz, A. & Wysocki, H. Association of atrial fibrillation and focal neurologic deficits with impaired cognitive function in hospitalized patients >or =65 years of age. Am. J. Cardiol. 98, 1238–1241 (2006).

    PubMed  Google Scholar 

  148. Alonso, A. et al. Correlates of dementia and mild cognitive impairment in patients with atrial fibrillation: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). J. Am. Heart Assoc. 6, e006014 (2017).

    PubMed  PubMed Central  Google Scholar 

  149. Nishtala, A. et al. Atrial fibrillation and cognitive decline in the Framingham Heart Study. Heart Rhythm 15, 166–172 (2018).

    PubMed  Google Scholar 

Download references

Reviewer information

Nature Reviews Cardiology thanks S. Seshadri, M. A. Ikram, and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Authors and Affiliations

Authors

Contributions

M.M., J.G.-R., and B.J.G. researched data for the article and wrote the manuscript. All authors provided substantial contribution to the discussion of content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Malini Madhavan.

Ethics declarations

Competing interests

J.P.P. has received support from ARCA biopharma, Boston Scientific, GE Healthcare, and Johnson & Johnson/Janssen Scientific Affairs and from consultancies to Forest Laboratories, Janssen Scientific Affairs, Medtronic, Pfizer/Bristol Myers Squibb, and Spectranetics. B.J.G. receives modest support for consulting provided to Janssen Pharmaceuticals and Bristol-Myers Squibb. The other authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Madhavan, M., Graff-Radford, J., Piccini, J.P. et al. Cognitive dysfunction in atrial fibrillation. Nat Rev Cardiol 15, 744–756 (2018). https://doi.org/10.1038/s41569-018-0075-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-018-0075-z

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing