Advances in drug therapy for cognitive dysfunction associated with atrial fibrillation_West China Medical Journal

Authors：

ZHOU Xuan , RAO Li ,  ZHANG Xiaoling

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

ZHANG Xiaoling, Email: zhang_xiaoling@163.com

Keywords：

Atrial fibrillation; cognitive dysfunction; drug therapy

DOI：

10.7507/1002-0179.202407104

Video：

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Atrial fibrillation, as the most common arrhythmia currently, can lead to secondary post-stroke cognitive dysfunction and chronic brain damage through various pathways, increasing the risk of cognitive dysfunction and affecting patient prognosis. The prevention and treatment drugs for cognitive dysfunction associated with atrial fibrillation mainly include anticoagulants, heart rhythm and heart rate control drugs, statins, and antihypertensive drugs. At present, there is still some controversy over the medication for cognitive dysfunction associated with atrial fibrillation, lacking guidelines and expert consensus. It is urgent and necessary to find safe, economical, and effective drugs to improve the cognitive function of atrial fibrillation patients. This article summarizes the recent advances in drug therapy for cognitive dysfunction associated with atrial fibrillation, in order to provide a reference for the treatment of cognitive dysfunction associated with atrial fibrillation in clinical practice.

1.	Dai H, Zhang Q, Much AA, et al. Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990-2017: results from the Global Burden of Disease Study 2017. Eur Heart J Qual Care Clin Outcomes, 2021, 7(6): 574-582.
2.	Go AS, Hylek EM, Phillips KA, 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, 2001, 285(18): 2370-2375.
3.	Harvey PD. Domains of cognition and their assessment. Dialogues Clin Neurosci, 2019, 21(3): 227-237.
4.	Liu DS, Chen J, Jian WM, et al. The association of atrial fibrillation and dementia incidence: a meta-analysis of prospective cohort studies. J Geriatr Cardiol, 2019, 16(3): 298-306.
5.	Manolis TA, Manolis AA, Apostolopoulos EJ, et al. Atrial fibrillation and cognitive impairment: an associated burden or burden by association?. Angiology, 2020, 71(6): 498-519.
6.	Bunch TJ. Atrial fibrillation and dementia. Circulation, 2020, 142(7): 618-620.
7.	Gardarsdottir M, Sigurdsson S, Aspelund T, et al. Atrial fibrillation is associated with decreased total cerebral blood flow and brain perfusion. Europace, 2018, 20(8): 1252-1258.
8.	Junejo RT, Braz ID, Lucas SJE, et al. Impaired cerebrovascular reactivity in patients with atrial fibrillation. J Am Coll Cardiol, 2019, 73(10): 1230-1232.
9.	Varrias D, Saralidze T, Borkowski P, et al. Atrial fibrillation and dementia: pathophysiological mechanisms and clinical implications. Biomolecules, 2024, 14(4): 455.
10.	Zacharia E, Papageorgiou N, Ioannou A, et al. Inflammatory biomarkers in atrial fibrillation. Curr Med Chem, 2019, 26(5): 837-854.
11.	Conway DS, Lip GY. Inflammation, arrhythmia burden and the thrombotic consequences of atrial fibrillation. Eur Heart J, 2004, 25(19): 1761.
12.	Weinstein G, Seshadri S. Circulating biomarkers that predict incident dementia. Alzheimers Res Ther, 2014, 6(1): 6.
13.	Ihara K, Sasano T. Role of Inflammation in the pathogenesis of atrial fibrillation. Front Physiol, 2022, 13: 862164.
14.	Hu YF, Chen YJ, Lin YJ, et al. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol, 2015, 12(4): 230-243.
15.	Grossmann K. Anticoagulants for treatment of Alzheimer’s Disease. J Alzheimers Dis, 2020, 77(4): 1373-1382.
16.	Sirtori CR. The pharmacology of statins. Pharmacol Res, 2014, 88: 3-11.
17.	Lappegård KT, Pop-Purceleanu M, van Heerde W, et al. Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy. J Neuroinflammation, 2013, 10: 78.
18.	He L, Xu R, Wang J, et al. Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke. BMC Neurol, 2019, 19(1): 240.
19.	Eun MY, Jung JM, Choi KH, et al. Statin Effects in atrial fibrillation-related stroke: a systematic review and meta-analysis. Front Neurol, 2020, 11: 589684.
20.	Mongkhon P, Fanning L, Lau WCY, et al. Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: a population-based cohort study. Heart Rhythm, 2020, 17(5): 706-713.
21.	Ding M, Fratiglioni L, Johnell K, et al. Atrial fibrillation, antithrombotic treatment, and cognitive aging: a population-based study. Neurology, 2018, 91(19): e1732-e1740.
22.	Barber M, Tait RC, Scott J, et al. Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation. J Thromb Haemost, 2004, 2(11): 1873-1878.
23.	Yates PA, Villemagne VL, Ellis KA, et al. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol, 2014, 4: 205.
24.	Matsuo S, Nakamura Y, Kinoshita M. Warfarin reduces silent cerebral infarction in elderly patients with atrial fibrillation. Coron Artery Dis, 1998, 9(4): 223-226.
25.	Madhavan M, Hu TY, Gersh BJ, et al. Efficacy of warfarin anticoagulation and incident dementia in a community-based cohort of atrial fibrillation. Mayo Clin Proc, 2018, 93(2): 145-154.
26.	Mavaddat N, Roalfe A, Fletcher K, 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, 2014, 45(5): 1381-1386.
27.	Annweiler C, Ferland G, Barberger-Gateau P, et al. Vitamin K antagonists and cognitive impairment: results from a cross-sectional pilot study among geriatric patients. J Gerontol A Biol Sci Med Sci, 2015, 70(1): 97-101.
28.	Jacobs V, Woller SC, Stevens S, et al. Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia. Heart Rhythm, 2014, 11(12): 2206-2213.
29.	Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J, 2021, 42(5): 373-498.
30.	Yang E. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation-full speed ahead or proceed with caution?. Vasc Health Risk Manag, 2014, 10: 507-522.
31.	Schneeweiss S, Gagne JJ, Patrick AR, et al. Comparative efficacy and safety of new oral anticoagulants in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes, 2012, 5(4): 480-486.
32.	Lee KH, Yeh JT, Wu ML, et al. Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: a systematic review with meta-analysis and trial sequential analysis. Thromb Res, 2024, 238: 132-140.
33.	Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J, 2018, 39(6): 453-460.
34.	Caramelli B, Yu PC, Cardozo FAM, et al. Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial. BMC Med, 2022, 20(1): 374.
35.	Bezabhe WM, Bereznicki LR, Radford J, et al. Oral anticoagulant treatment and the risk of dementia in patients with atrial fibrillation: a population-based cohort study. J Am Heart Assoc, 2022, 11(7): e023098.
36.	Lee SR, Choi EK, Park SH, et al. Comparing warfarin and 4 direct oral anticoagulants for the risk of dementia in patients with atrial fibrillation. Stroke, 2021, 52(11): 3459-3468.
37.	Damanti S, Pasina L, Cortesi L, et al. Atrial fibrillation: possible influences of rate and rhythm control strategy on cognitive performance. J Am Geriatr Soc, 2018, 66(11): 2178-2182.
38.	Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet, 2000, 356(9242): 1627-1631.
39.	Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol, 2000, 57(10): 1439-1443.
40.	Zhu XC, Dai WZ, Ma T. Overview the effect of statin therapy on dementia risk, cognitive changes and its pathologic change: a systematic review and meta-analysis. Ann Transl Med, 2018, 6(22): 435.
41.	Chao TF, Liu CJ, Chen SJ, et al. Statins and the risk of dementia in patients with atrial fibrillation: a nationwide population-based cohort study. Int J Cardiol, 2015, 196: 91-97.
42.	Tendolkar I, Enajat M, Zwiers MP, et al. One-year cholesterol lowering treatment reduces medial temporal lobe atrophy and memory decline in stroke-free elderly with atrial fibrillation: evidence from a parallel group randomized trial. Int J Geriatr Psychiatry, 2012, 27(1): 49-58.
43.	Kuang ZM. Effect of combined antihypertensive and lipid-lowering therapies on cognitive function: a new treatment strategy?. Cardiol Res Pract, 2020, 2020: 1484357.
44.	Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension. Circ Res, 2019, 124(7): 1025-1044.
45.	Antonazzo B, Marano G, Romagnoli E, et al. Impact of arterial hypertension and its management strategies on cognitive function and dementia: a comprehensive umbrella review. Minerva Cardiol Angiol, 2022, 70(3): 285-297.
46.	Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med, 2003, 163(9): 1069-1075.

1. Dai H, Zhang Q, Much AA, et al. Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990-2017: results from the Global Burden of Disease Study 2017. Eur Heart J Qual Care Clin Outcomes, 2021, 7(6): 574-582.
2. Go AS, Hylek EM, Phillips KA, 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, 2001, 285(18): 2370-2375.
3. Harvey PD. Domains of cognition and their assessment. Dialogues Clin Neurosci, 2019, 21(3): 227-237.
4. Liu DS, Chen J, Jian WM, et al. The association of atrial fibrillation and dementia incidence: a meta-analysis of prospective cohort studies. J Geriatr Cardiol, 2019, 16(3): 298-306.
5. Manolis TA, Manolis AA, Apostolopoulos EJ, et al. Atrial fibrillation and cognitive impairment: an associated burden or burden by association?. Angiology, 2020, 71(6): 498-519.
6. Bunch TJ. Atrial fibrillation and dementia. Circulation, 2020, 142(7): 618-620.
7. Gardarsdottir M, Sigurdsson S, Aspelund T, et al. Atrial fibrillation is associated with decreased total cerebral blood flow and brain perfusion. Europace, 2018, 20(8): 1252-1258.
8. Junejo RT, Braz ID, Lucas SJE, et al. Impaired cerebrovascular reactivity in patients with atrial fibrillation. J Am Coll Cardiol, 2019, 73(10): 1230-1232.
9. Varrias D, Saralidze T, Borkowski P, et al. Atrial fibrillation and dementia: pathophysiological mechanisms and clinical implications. Biomolecules, 2024, 14(4): 455.
10. Zacharia E, Papageorgiou N, Ioannou A, et al. Inflammatory biomarkers in atrial fibrillation. Curr Med Chem, 2019, 26(5): 837-854.
11. Conway DS, Lip GY. Inflammation, arrhythmia burden and the thrombotic consequences of atrial fibrillation. Eur Heart J, 2004, 25(19): 1761.
12. Weinstein G, Seshadri S. Circulating biomarkers that predict incident dementia. Alzheimers Res Ther, 2014, 6(1): 6.
13. Ihara K, Sasano T. Role of Inflammation in the pathogenesis of atrial fibrillation. Front Physiol, 2022, 13: 862164.
14. Hu YF, Chen YJ, Lin YJ, et al. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol, 2015, 12(4): 230-243.
15. Grossmann K. Anticoagulants for treatment of Alzheimer’s Disease. J Alzheimers Dis, 2020, 77(4): 1373-1382.
16. Sirtori CR. The pharmacology of statins. Pharmacol Res, 2014, 88: 3-11.
17. Lappegård KT, Pop-Purceleanu M, van Heerde W, et al. Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy. J Neuroinflammation, 2013, 10: 78.
18. He L, Xu R, Wang J, et al. Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke. BMC Neurol, 2019, 19(1): 240.
19. Eun MY, Jung JM, Choi KH, et al. Statin Effects in atrial fibrillation-related stroke: a systematic review and meta-analysis. Front Neurol, 2020, 11: 589684.
20. Mongkhon P, Fanning L, Lau WCY, et al. Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: a population-based cohort study. Heart Rhythm, 2020, 17(5): 706-713.
21. Ding M, Fratiglioni L, Johnell K, et al. Atrial fibrillation, antithrombotic treatment, and cognitive aging: a population-based study. Neurology, 2018, 91(19): e1732-e1740.
22. Barber M, Tait RC, Scott J, et al. Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation. J Thromb Haemost, 2004, 2(11): 1873-1878.
23. Yates PA, Villemagne VL, Ellis KA, et al. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol, 2014, 4: 205.
24. Matsuo S, Nakamura Y, Kinoshita M. Warfarin reduces silent cerebral infarction in elderly patients with atrial fibrillation. Coron Artery Dis, 1998, 9(4): 223-226.
25. Madhavan M, Hu TY, Gersh BJ, et al. Efficacy of warfarin anticoagulation and incident dementia in a community-based cohort of atrial fibrillation. Mayo Clin Proc, 2018, 93(2): 145-154.
26. Mavaddat N, Roalfe A, Fletcher K, 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, 2014, 45(5): 1381-1386.
27. Annweiler C, Ferland G, Barberger-Gateau P, et al. Vitamin K antagonists and cognitive impairment: results from a cross-sectional pilot study among geriatric patients. J Gerontol A Biol Sci Med Sci, 2015, 70(1): 97-101.
28. Jacobs V, Woller SC, Stevens S, et al. Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia. Heart Rhythm, 2014, 11(12): 2206-2213.
29. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J, 2021, 42(5): 373-498.
30. Yang E. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation-full speed ahead or proceed with caution?. Vasc Health Risk Manag, 2014, 10: 507-522.
31. Schneeweiss S, Gagne JJ, Patrick AR, et al. Comparative efficacy and safety of new oral anticoagulants in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes, 2012, 5(4): 480-486.
32. Lee KH, Yeh JT, Wu ML, et al. Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: a systematic review with meta-analysis and trial sequential analysis. Thromb Res, 2024, 238: 132-140.
33. Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J, 2018, 39(6): 453-460.
34. Caramelli B, Yu PC, Cardozo FAM, et al. Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial. BMC Med, 2022, 20(1): 374.
35. Bezabhe WM, Bereznicki LR, Radford J, et al. Oral anticoagulant treatment and the risk of dementia in patients with atrial fibrillation: a population-based cohort study. J Am Heart Assoc, 2022, 11(7): e023098.
36. Lee SR, Choi EK, Park SH, et al. Comparing warfarin and 4 direct oral anticoagulants for the risk of dementia in patients with atrial fibrillation. Stroke, 2021, 52(11): 3459-3468.
37. Damanti S, Pasina L, Cortesi L, et al. Atrial fibrillation: possible influences of rate and rhythm control strategy on cognitive performance. J Am Geriatr Soc, 2018, 66(11): 2178-2182.
38. Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet, 2000, 356(9242): 1627-1631.
39. Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol, 2000, 57(10): 1439-1443.
40. Zhu XC, Dai WZ, Ma T. Overview the effect of statin therapy on dementia risk, cognitive changes and its pathologic change: a systematic review and meta-analysis. Ann Transl Med, 2018, 6(22): 435.
41. Chao TF, Liu CJ, Chen SJ, et al. Statins and the risk of dementia in patients with atrial fibrillation: a nationwide population-based cohort study. Int J Cardiol, 2015, 196: 91-97.
42. Tendolkar I, Enajat M, Zwiers MP, et al. One-year cholesterol lowering treatment reduces medial temporal lobe atrophy and memory decline in stroke-free elderly with atrial fibrillation: evidence from a parallel group randomized trial. Int J Geriatr Psychiatry, 2012, 27(1): 49-58.
43. Kuang ZM. Effect of combined antihypertensive and lipid-lowering therapies on cognitive function: a new treatment strategy?. Cardiol Res Pract, 2020, 2020: 1484357.
44. Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension. Circ Res, 2019, 124(7): 1025-1044.
45. Antonazzo B, Marano G, Romagnoli E, et al. Impact of arterial hypertension and its management strategies on cognitive function and dementia: a comprehensive umbrella review. Minerva Cardiol Angiol, 2022, 70(3): 285-297.
46. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med, 2003, 163(9): 1069-1075.

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