Original article
Vol. 156 No. 1 (2026)
Brain lesions and cognitive decline in patients with atrial fibrillation: a prospective multicentre cohort study
-
Cite this as:
-
Swiss Med Wkly. 2026;156:4059
-
Published
-
09.01.2026
Summary
STUDY AIM: Atrial fibrillation (AF) is associated with a high burden of vascular brain lesions, most of which are covert. We aimed to assess the association between vascular brain lesions (brain infarcts, microbleeds, white matter lesions) and cognitive decline over time in atrial fibrillation patients.
METHODS: We included 1536 atrial fibrillation patients with brain magnetic resonance imaging (MRI) from a prospective multicentre cohort study. Patients were enrolled between 2014 and 2017 across 14 centres in Switzerland. Their cognitive functioning was assessed at baseline and yearly intervals using Montreal Cognitive Assessment (MoCA) and Cognitive Construct (CoCo) scores. Cognitive decline was defined as a score decline of >1 standard deviation of the age- and education-standardised baseline population compared with individual baseline levels of the corresponding test.
RESULTS: Of 1536 patients, 1030 (mean age: 72 years; 73% male) had ≥1 vascular brain lesion on baseline MRI. During a median follow-up of 5.13 years, cognitive decline developed in 159 (10%) patients based on MoCA scores and in 144 (9%) based on CoCo scores. The incidence rate (per 100 person-years) for cognitive decline was 3.64 in patients with brain lesions vs 1.82 in patients without brain lesions on baseline MRI using MoCA scores, and 3.18 vs 2.0 using CoCo scores. In multivariable adjusted Cox proportional hazard models, the hazard ratio (HR) (95% confidence interval [CI]) of any brain lesion for cognitive decline was 1.29 (0.85–1.96) using the MoCA and 1.45 (0.95–2.20) using the CoCo score.
CONCLUSIONS: In our atrial fibrillation cohort, the presence of brain lesions was not associated with a higher risk of cognitive decline using the MoCA or the CoCo score. However, there was an association with more-specific cognitive domains.
Trial registration: https://clinicaltrials.gov NCT02105844.
References
- 1. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al.; Alzheimer’s Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec;366(9503):2112–7. 10.1016/S0140-6736(05)67889-0
- 2. Nichols E, Szoeke CE, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al.; GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Jan;18(1):88–106. 10.1016/S1474-4422(18)30403-4
- 3. Prince MJ. World Alzheimer report 2015: the global impact of dementia. [Internet]. Available from: https://www.alzint.org/u/WorldAlzheimerReport2015.pdf
- 4. Raz L, Knoefel J, Bhaskar K. The neuropathology and cerebrovascular mechanisms of dementia. J Cereb Blood Flow Metab. 2016 Jan;36(1):172–86. 10.1038/jcbfm.2015.164
- 5. Ott A, Breteler MM, de Bruyne MC, van Harskamp F, Grobbee DE, Hofman A. Atrial fibrillation and dementia in a population-based study. The Rotterdam Study. Stroke. 1997 Feb;28(2):316–21. https://doi.org/10.1161/01.STR.28.2.316
- 6. Diener HC, Hart RG, Koudstaal PJ, Lane DA, Lip GY. Atrial Fibrillation and Cognitive Function: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Feb;73(5):612–9. doi: https://doi.org/10.1016/j.jacc.2018.10.077
- 7. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al.; ESC Scientific Document Group. 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 Feb;42(5):373–498. 10.1093/eurheartj/ehaa612
- 8. Koh YH, Lew LZ, Franke KB, Elliott AD, Lau DH, Thiyagarajah A, et al. Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals. Europace. 2022 Sep;24(8):1229–39. 10.1093/europace/euac003
- 9. Conen D, Rodondi N, Mueller A, Beer J, Auricchio A, Ammann P, et al. Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation. Swiss Med Wkly. 2017 Jul;147(2728):w14467. 10.4414/smw.2017.14467
- 10. Conen D, Rodondi N, Müller A, Beer JH, Ammann P, Moschovitis G, et al.; Swiss-AF Study Investigators. Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2019 Mar;73(9):989–99. 10.1016/j.jacc.2018.12.039
- 11. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al.; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672–713. 10.1161/STR.0b013e3182299496
- 12. Silbert LC, Nelson C, Howieson DB, Moore MM, Kaye JA. Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline. Neurology. 2008 Jul;71(2):108–13. 10.1212/01.wnl.0000316799.86917.37
- 13. Kühne M, Krisai P, Coslovsky M, Rodondi N, Müller A, Beer JH, et al.; Swiss-AF Investigators. Silent brain infarcts impact on cognitive function in atrial fibrillation. Eur Heart J. 2022 Jun;43(22):2127–35. 10.1093/eurheartj/ehac020
- 14. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al.; European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369–429. 10.1093/eurheartj/ehq278
- 15. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149(2):351–6. 10.2214/ajr.149.2.351
- 16. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695–9. 10.1111/j.1532-5415.2005.53221.x
- 17. Arbuthnott K, Frank J. Trail making test, part B as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol. 2000 Aug;22(4):518–28. doi: https://doi.org/10.1076/1380-3395(200008)22:4;1-0;FT518
- 18. Bowie CR, Harvey PD. Administration and interpretation of the Trail Making Test. Nat Protoc. 2006;1(5):2277–81. 10.1038/nprot.2006.390
- 19. Springer A, Monsch AU, Dutilh G, Coslovsky M, Kievit RA, Bonati LH, et al.; Swiss-AF Study Investigators. A factor score reflecting cognitive functioning in patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF). PLoS One. 2020 Oct;15(10):e0240167. 10.1371/journal.pone.0240167
- 20. Wang S, Blazer DG. Depression and cognition in the elderly. Annu Rev Clin Psychol. 2015;11(1):331–60. doi: https://doi.org/10.1146/annurev-clinpsy-032814-112828
- 21. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37–49. 10.1016/0022-3956(82)90033-4
- 22. Laudisio A, Antonelli Incalzi R, Gemma A, Marzetti E, Pozzi G, Padua L, et al. Definition of a Geriatric Depression Scale cutoff based upon quality of life: a population-based study. Int J Geriatr Psychiatry. 2018 Jan;33(1):e58–64. 10.1002/gps.4715
- 23. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003 Mar;348(13):1215–22. 10.1056/NEJMoa022066
- 24. Friberg L, Andersson T, Rosenqvist M. Less dementia and stroke in low-risk patients with atrial fibrillation taking oral anticoagulation. Eur Heart J. 2019 Jul;40(28):2327–35. 10.1093/eurheartj/ehz304
- 25. Rosano C, Perera S, Inzitari M, Newman AB, Longstreth WT, Studenski S. Digit Symbol Substitution test and future clinical and subclinical disorders of cognition, mobility and mood in older adults. Age Ageing. 2016 Sep;45(5):688–95. 10.1093/ageing/afw116
- 26. Wang S, Jiaerken Y, Yu X, Shen Z, Luo X, Hong H, et al. Understanding the association between psychomotor processing speed and white matter hyperintensity: A comprehensive multi-modality MR imaging study. Hum Brain Mapp. 2020 Feb;41(3):605–16. 10.1002/hbm.24826
- 27. Jaeger J. Digit Symbol Substitution Test: The Case for Sensitivity Over Specificity in Neuropsychological Testing. J Clin Psychopharmacol. 2018 Oct;38(5):513–9. 10.1097/JCP.0000000000000941
- 28. Baudouin A, Clarys D, Vanneste S, Isingrini M. Executive functioning and processing speed in age-related differences in memory: contribution of a coding task. Brain Cogn. 2009 Dec;71(3):240–5. 10.1016/j.bandc.2009.08.007
- 29. Torralva T, Laffaye T, Báez S, Gleichgerrcht E, Bruno D, Chade A, et al. Verbal Fluency as a Rapid Screening Test for Cognitive Impairment in Early Parkinson’s Disease. J Neuropsychiatry Clin Neurosci. 2015;27(3):244–7. 10.1176/appi.neuropsych.14060139
- 30. Chen LY, Norby FL, Gottesman RF, Mosley TH, Soliman EZ, Agarwal SK, et al. Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20 Years: The ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). J Am Heart Assoc. 2018 Mar;7(6):e007301. 10.1161/JAHA.117.007301
- 31. Alvarez JA, Emory E. Executive function and the frontal lobes: a meta-analytic review. Neuropsychol Rev. 2006 Mar;16(1):17–42. doi: https://doi.org/10.1007/s11065-006-9002-x
- 32. Tullberg M, Fletcher E, DeCarli C, Mungas D, Reed BR, Harvey DJ, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology. 2004 Jul;63(2):246–53. doi: https://doi.org/10.1212/01.WNL.0000130530.55104.B5
- 33. Diamond A, Ling DS. Conclusions about interventions, programs, and approaches for improving executive functions that appear justified and those that, despite much hype, do not. Dev Cogn Neurosci. 2016 Apr;18:34–48. 10.1016/j.dcn.2015.11.005
- 34. Krisai P, Eken C, Aeschbacher S, Coslovsky M, Rolny V, Carmine D, et al.; Swiss-AF study investigators. Biomarkers, Clinical Variables, and the CHA2DS2-VASc Score to Detect Silent Brain Infarcts in Atrial Fibrillation Patients. J Stroke. 2021 Sep;23(3):449–52. 10.5853/jos.2021.02068
- 35. Bunch TJ, Steinberg BA. Rhythm Matters When It Comes to Brain Perfusion. JACC. Clinical electrophysiology. 2022;8(11):1378-1380. 10.1016/j.jacep.2022.08.017
- 36. Saglietto A, Scarsoglio S, Canova D, Roatta S, Gianotto N, Piccotti A, et al. Increased beat-to-beat variability of cerebral microcirculatory perfusion during atrial fibrillation: a near-infrared spectroscopy study. Europace. 2021 Aug;23(8):1219–26. 10.1093/europace/euab070
- 37. Savelieva I, Fumagalli S, Kenny RA, Anker S, Benetos A, Boriani G, et al. EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA). Europace. 2023 Apr;25(4):1249–76. 10.1093/europace/euac123
- 38. Aeschbacher S, Blum S, Meyre PB, Coslovsky M, Vischer AS, Sinnecker T, et al. Blood Pressure and Brain Lesions in Patients With Atrial Fibrillation. Hypertens (Dallas, Tex 1979). 2021 Feb;77(2):662-671. doi: 10.1161/HYPERTENSIONAHA.120.16025.
- 39. Lane DA, Raichand S, Moore D, Connock M, Fry-Smith A, Fitzmaurice DA; Steering Committee. Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review. Health Technol Assess. 2013 Jul;17(30):1–188. 10.3310/hta17300