Atrial fibrillation in aging; methodological aspects and the relation to dementia and cerebral vascular disease

Emerging evidence suggest an increased risk of dementia in individuals with atrial fibrillation (AF). However, until recently, few studies have investigated the relation between AF and dementia taking both prevalent and incident stroke into account. Therefore, this thesis aims to examine if AF increase the risk of dementia in a sample free from a history of stroke at baseline and incident stroke during follow-up. Further, the mechanisms behind an association between AF and dementia in the absence of symptomatic stroke is not elucidated. Therefore, this thesis also aims to examine if AF is associated to silent brain infarcts (SBIs) and small vessel disease on brain MRI. Since epidemiological studies often are accompanied with biases, we also analyzed differential attrition during follow-up and agreement between self- and proxy-reported diagnoses. Data were obtained from the Gothenburg H70 Birth Cohort (H70) studies and the Prospective Population Study of Women (PPSW) in Gothenburg. The samples used in this thesis include the cohorts born 1930 (followed from age 70 to 88) and 1944 (examined at age 70). The H70 and PPSW studies are comprehensive population-based studies aiming to be representative of older adults living in Gothenburg, Sweden. We found that a history of AF at age 70 increased the risk of dementia during follow-up in the 1930 cohort. Further, we found that AF was cross-sectionally associated to symptomatic stroke, SBIs, and lacunes among 70-year-olds in the 1944 cohort. There were no associations between AF and global white matter hyperintensity (WMH) volumes or the presence of any cerebral microbleed. However, among participants with symptomatic stroke, AF was associated with larger WMH volumes. In the 1930 cohort, both AF and dementia were associated with attrition due to death. Further, agreement between self- and proxy-reported diagnoses was substantial for AF, myocardial infarction, angina pectoris, hypertension, and diabetes mellitus, but only fair for heart failure and intermittent claudication. Further research is needed to investigate the mechanism(s) behind the association between AF and dementia, the optimal treatment regimens for AF in relation to dementia prevention, and possibilities to include brain MRI in treatment guidelines to further personalize anticoagulation treatment in AF patients. In addition, analyzing differential attrition and diagnostic accuracy in epidemiologic research is necessary to evaluate and generalize results