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      Atrial fibrillation, antithrombotic treatment, and cognitive aging : A population-based study

      research-article
      , MSc , , MD, PhD, , PhD, , PhD, , PhD, , MD, PhD, , MD, PhD, , PhD
      Neurology
      Lippincott Williams & Wilkins

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          Abstract

          Objective

          To examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.

          Methods

          This population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001–2004 to 2010–2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.

          Results

          We identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (β coefficient = −0.24, 95% confidence interval [CI]: −0.31 to −0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11–1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09–3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92–1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18–0.92).

          Conclusion

          AF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.

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          Most cited references30

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          Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

          Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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            Global epidemiology of atrial fibrillation.

            Atrial fibrillation (AF) is a major public health burden worldwide, and its prevalence is set to increase owing to widespread population ageing, especially in rapidly developing countries such as Brazil, China, India, and Indonesia. Despite the availability of epidemiological data on the prevalence of AF in North America and Western Europe, corresponding data are limited in Africa, Asia, and South America. Moreover, other observations suggest that the prevalence of AF might be underestimated-not only in low-income and middle-income countries, but also in their high-income counterparts. Future studies are required to provide precise estimations of the global AF burden, identify important risk factors in various regions worldwide, and take into consideration regional and ethnic variations in AF. Furthermore, in response to the increasing prevalence of AF, additional resources will need to be allocated globally for prevention and treatment of AF and its associated complications. In this Review, we discuss the available data on the global prevalence, risk factors, management, financial costs, and clinical burden of AF, and highlight the current worldwide inadequacy of its treatment.
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              Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches.

              A central problem in public health studies is how to make inferences about the causal effects of treatments or agents. In this article we review an approach to making such inferences via potential outcomes. In this approach, the causal effect is defined as a comparison of results from two or more alternative treatments, with only one of the results actually observed. We discuss the application of this approach to a number of data collection designs and associated problems commonly encountered in clinical research and epidemiology. Topics considered include the fundamental role of the assignment mechanism, in particular the importance of randomization as an unconfounded method of assignment; randomization-based and model-based methods of statistical inference for causal effects; methods for handling noncompliance and missing data; and methods for limiting bias in the analysis of observational data, including propensity score matching and sensitivity analysis.
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                Author and article information

                Contributors
                Journal
                Neurology
                Neurology
                neurology
                neur
                neurology
                NEUROLOGY
                Neurology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0028-3878
                1526-632X
                06 November 2018
                06 November 2018
                : 91
                : 19
                : e1732-e1740
                Affiliations
                From the Aging Research Center (M.D., L.F., K.J., G.S., J.F., A.M., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University; Stockholm Gerontology Research Center (L.F.), Stockholm; Institute of Environmental Medicine (P.L.), Karolinska Institutet, Stockholm; Department of Cardiology (P.L.), Danderyd Hospital, Stockholm, Sweden; and Department of Clinical and Experimental Sciences (A.M.), University of Brescia, Italy.
                Author notes
                Correspondence Mozhu Ding mozhu.ding@ 123456ki.se

                Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

                The Article Processing Charge was funded by the Swedish Research Council.

                Article
                NEUROLOGY2018878603
                10.1212/WNL.0000000000006456
                6251601
                30305443
                fea22668-5205-4329-8a44-a3e71d4f24aa
                Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

                This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 January 2018
                : 23 July 2018
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