Investigating the Contributions of Blood-Brain Barrier Dysfunction to the Risk of Cognitive Decline and Dementia in Individuals with Atrial Fibrillation

Abstract

Despite evidence for an association between atrial fibrillation (AF) and cognitive decline and dementia independent of stroke, pathways underlying this relationship remain unclear. Critically, elevated levels of inflammatory markers, common in AF, are associated with the breakdown of the blood-brain barrier (BBB) and may contribute to neuroinflammation and neurodegeneration. To investigate this potential contributing pathway, we estimated associations of inflammatory markers with cognitive decline and dementia in AF adults. We used data from two population-based cohorts and found that inflammatory markers were associated with cognitive decline but not dementia. Some associations were modified by sex and apolipoprotein E (APOE) genotype. These findings provide preliminary evidence for inflammatory-mediated BBB dysfunction as a potential contributing pathway linking AF to cognitive decline. Future work examining the role of BBB dysfunction in AF and cognition may benefit from the use of markers of central inflammation to increase sensitivity, while considering possible differences by sex, dementia subtype, and APOE genotype.