Atrial fibrillation, antithrombotic treatment, and cognitive aging

Abstract

ObjectiveTo 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.MethodsThis 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.ResultsWe 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).ConclusionAF 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.

Aiding the discovery of new treatments for dementia by uncovering unknown benefits of existing medications

“…results (data not shown). This finding is consistent with recent studies that have found similar, large protective effects of anticoagulants on the onset of dementia [27,28], which could be through maintaining cerebral blood flow and decreasing the risk of vascular damage to the brain. Most evidence supporting this association is based on observational research within patients having atrial fibrillation; further evidence from a variety of data sources and a broader population is warranted.…”

Atrial fibrillation increases the risk of dementia amongst older adults even in the absence of stroke

“…We found that atrial fibrillation was associated with dementia in men, but not in women. In contrast to our study, the Swedish Kungsholmen study found that atrial fibrillation (after stratifying for sex) was associated with dementia in women, but not in men and one register‐based study from Taiwan found similar risk for dementia in men and women with atrial fibrillation . Our finding that prevalence for atrial fibrillation was higher in men than women is in line with other studies from North America and Europe .…”

“…We found a somewhat higher risk (HR 2.9; 95% CI: 1.2–6.8) in our stroke‐free sample than the Whitehall II study (HR 1.67; 95% CI: 1.17, 2.38) and the Adult Changes in Thought (ACT) Study (HR 1.40; 95% CI: 1.08, 1.82) , which also excluded participants with incident stroke. Other community or population‐based studies, taking incident stroke into account by censoring participants at the time of a clinical stroke or adjusting for incident stroke , have shown similar results as the Whitehall II and ACT studies (HR 1.23–1.48).…”

“…In 1998, the population‐based Rotterdam study found a cross‐sectional association between atrial fibrillation and dementia both in the presence and absence of stroke . Since then, a number of prospective studies have shown associations between atrial fibrillation and incident dementia , with some exceptions . However, few studies have excluded participants with stroke during the whole study period.…”

“…One well‐known genetic risk factor for AD pathology is the APOE ε4 allele. However, the few studies investigating the modifying effect of the APOE ε4 allele on the association between atrial fibrillation and dementia show conflicting results . Another gene of possible importance for dementia is the angiotensin‐converting enzyme ( ACE ) gene, encoding an enzyme involved in the renin–angiotensin–aldosterone system (RAAS) .…”