Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy.

AIMS To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. METHODS AND RESULTS We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. CONCLUSION Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.

[1]  R. J. McDonald,et al.  Enhanced cell death and learning deficits after a mini-stroke in aged hippocampus , 2008, Neurobiology of Aging.

[2]  E. Ringelstein,et al.  High-Normal Blood Pressure Is Associated With Poor Cognitive Performance , 2008, Hypertension.

[3]  S. Lupien,et al.  The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition , 2007, Brain and Cognition.

[4]  R. Green,et al.  Vascular factors predict rate of progression in Alzheimer disease , 2007, Neurology.

[5]  Bertil Olsson,et al.  Outcome parameters for trials in atrial fibrillation: executive summary. , 2007, European heart journal.

[6]  Christian Enzinger,et al.  Section Editor: Progression of Leukoaraiosis and Cognition , 2022 .

[7]  S. Resnick,et al.  Longitudinal Changes in Cerebral Blood Flow in the Older Hypertensive Brain , 2007, Stroke.

[8]  M. Albert,et al.  Neuropsychological measures in normal individuals that predict subsequent cognitive decline. , 2007, Archives of neurology.

[9]  R. Sulkava,et al.  Atrial Fibrillation, Stroke, and Cognition: A Longitudinal Population-Based Study of People Aged 85 and Older , 2007, Stroke.

[10]  J. Seward,et al.  Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a community-based cohort. , 2007, European heart journal.

[11]  R. Thomson,et al.  Non-valvular atrial fibrillation and cognitive decline: a longitudinal cohort study. , 2007, Age and ageing.

[12]  F Fazekas,et al.  Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[13]  G. Ravaglia,et al.  Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI). , 2007, Archives of gerontology and geriatrics.

[14]  A. Wykrętowicz,et al.  Association of atrial fibrillation and focal neurologic deficits with impaired cognitive function in hospitalized patients >or=65 years of age. , 2006, The American journal of cardiology.

[15]  E. D. Haan,et al.  Early cognitive impairment predicts long-term depressive symptoms and quality of life after stroke , 2006, Journal of the Neurological Sciences.

[16]  R. D'Agostino,et al.  Atrial fibrillation is associated with lower cognitive performance in the Framingham offspring men. , 2006, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[17]  G. Ravaglia,et al.  Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment , 2006, Neurological research.

[18]  P. Martínez-Martín.  [Impact of the cognitive impairment on the quality of life in patients with Parkinson's disease]. , 2006, Revista de neurologia.

[19]  P. Sachdev,et al.  Brain reserve and cognitive decline: a non-parametric systematic review , 2006, Psychological Medicine.

[20]  Hanna Damasio,et al.  Correlations between Regional Brain Volumes and Memory Performance in Anoxia , 2006, Journal of clinical and experimental neuropsychology.

[21]  Martin Hautzinger,et al.  Beck Depressions-Inventar , 2006 .

[22]  Pablo Martínez Martín.  Repercusiones sobre la calidad de vida del deterioro cognitivo en la enfermedad de Parkinson , 2006 .

[23]  D. Leys,et al.  Stroke Syndromes: Poststroke dementia , 2001 .

[24]  P. Matthews,et al.  White matter lesion progression, brain atrophy, and cognitive decline: The Austrian stroke prevention study , 2005, Annals of neurology.

[25]  Shen Fei,et al.  Poststroke Dementia , 2005 .

[26]  P. Wieacker,et al.  Novel and Recurrent Mutations in Patients with Androgen Insensitivity Syndromes , 2005, Hormone Research in Paediatrics.

[27]  B. Lüderitz,et al.  Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging. , 2005, Journal of the American College of Cardiology.

[28]  R. Jung.  Neuropsychological Assessment, 4th ed. , 2005 .

[29]  Thomas Wolbers,et al.  Hippocampus activity differentiates good from poor learners of a novel lexicon , 2005, NeuroImage.

[30]  P. J. Koudstaal,et al.  Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe , 2005, Neurology.

[31]  T. Yamashita,et al.  Progressive nature of paroxysmal atrial fibrillation. Observations from a 14-year follow-up study. , 2004, Circulation journal : official journal of the Japanese Circulation Society.

[32]  D. Stott,et al.  Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation , 2004, Journal of thrombosis and haemostasis : JTH.

[33]  P. Elias,et al.  Blood Pressure-Related Cognitive Decline: Does Age Make a Difference? , 2004, Hypertension.

[34]  K. Okumura,et al.  Prothrombotic activity is increased in patients with nonvalvular atrial fibrillation and risk factors for embolism. , 2004, Chest.

[35]  D. Levy,et al.  Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study , 2004, Circulation.

[36]  T. Strandberg,et al.  Predictors of cognitive decline and mortality of aged people over a 10-year period. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[37]  Atrial Fibrillation and Hypercoagulability: Dependent on Clinical Factors or/and on Genetic Alterations? , 2003, Journal of Thrombosis and Thrombolysis.

[38]  J R Hodges,et al.  Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia. , 2004, Journal of neurology, neurosurgery, and psychiatry.

[39]  G. Lip,et al.  Atrial Fibrillation and the Hypercoagulable State: From Basic Science to Clinical Practice , 2003, Pathophysiology of Haemostasis and Thrombosis.

[40]  S. DeKosky,et al.  Looking Backward to Move Forward: Early Detection of Neurodegenerative Disorders , 2003, Science.

[41]  David A. Snowdon,et al.  Healthy Aging and Dementia: Findings from the Nun Study , 2003, Annals of Internal Medicine.

[42]  G. Lip,et al.  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 , 2003, Circulation.

[43]  Asymptomatic embolisation in non-valvular atrial fibrillation and its relationship to anticoagulation therapy. , 2002, European journal of ultrasound : official journal of the European Federation of Societies for Ultrasound in Medicine and Biology.

[44]  Erin D Bigler,et al.  Temporal lobe morphology in normal aging and traumatic brain injury. , 2002, AJNR. American journal of neuroradiology.

[45]  E. Kumral,et al.  Microembolic Signal Detection in Patients with Symptomatic and Asymptomatic Lone Atrial Fibrillation , 2001, Cerebrovascular Diseases.

[46]  P. Maeder,et al.  Atrial fibrillation with small subcortical infarcts , 2001, Journal of neurology, neurosurgery, and psychiatry.

[47]  E. Ringelstein,et al.  Ultrasound contrast enhancing agents in neurosonology: principles, methods,future possibilities , 2000, Acta neurologica Scandinavica.

[48]  G. Frisoni,et al.  Atrial Fibrillation and Cognitive Disorders in Older People , 2000, Journal of the American Geriatrics Society.

[49]  I. Robertson,et al.  Atrial fibrillation and cognitive function: case-control study , 1998, Journal of neurology, neurosurgery, and psychiatry.

[50]  L. Lind,et al.  Atrial fibrillation is an independent determinant of low cognitive function: a cross-sectional study in elderly men. , 1998, Stroke.

[51]  C. Mariani,et al.  Neuropsychological deficits in asymptomatic atrial fibrillation , 1997, Acta neurologica Scandinavica.

[52]  M. Borggrefe,et al.  Intracranial microembolic signals in 500 patients with potential cardiac or carotid embolic source and in normal controls. , 1997, Stroke.

[53]  A Hofman,et al.  Atrial fibrillation and dementia in a population-based study. The Rotterdam Study. , 1997, Stroke.

[54]  A. Iorio,et al.  Silent lacunar infarcts in elderly patients with chronic non valvular atrial fibrillation , 1996, Aging.

[55]  S M Nazarian,et al.  Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. , 1992, The New England journal of medicine.

[56]  P. Wolf,et al.  Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. , 1991, Stroke.

[57]  K. Skullerud.  Variations in the size of the human brain. Influence of age, sex, body length, body mass index, alcoholism, Alzheimer changes, and cerebral atherosclerosis. , 1985, Acta neurologica Scandinavica. Supplementum.

[58]  A. Belanger,et al.  The Framingham study. , 1976, British medical journal.

[59]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[60]  Silvia G. Priori,et al.  ACC/AHA/ESC 2006 guidelines 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 European society of cardiology committee for PRAC , 2006 .