Atrial fibrillation/atrial flutter and reduced volumes of the hippocampus, amygdala, and thalamus: evidence from a community-based MRI study

Introduction: Atrial fibrillation (AF) is associated with cognitive decline and dementia even in the absence of clinical stroke, potentially through mechanisms such as silent infarction, small-vessel disease, hypoperfusion, and systemic inflammation. However, most previous studies have focused on global brain measures, and little is known about region-specific structural alterations, particularly within deep gray-matter structures and hippocampal subfields. Evidence regarding atrial flutter (AFL) remains limited. This study aimed to investigate the association between AF/AFL and regional brain and hippocampal subfield volumes in cognitively normal older adults. Materials and methods: This cross-sectional analysis included 7,074 community-dwelling participants aged ≥65 years from the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). Structural magnetic resonance imaging with 3D T1-weighted images was processed using FreeSurfer 7.0. Volumes of the cortex, cortical white matter, subcortical gray matter, eight regional brain areas, and hippocampal subfields were evaluated. AF/AFL was identified using electrocardiography. Adjusted mean regional brain volumes and 95% confidence intervals (CIs) were estimated using analysis of covariance. The false discovery rate was controlled using the Benjamini-Hochberg method. Additional exploratory analyses based on self-reported AF history were also performed. Stratified analyses were performed by age (<75 vs. ≥75 years) and sex. Results: After multivariable adjustment, AF/AFL (171 participants, 2.4%) was associated with smaller volumes of the cortex, cortical white matter, and subcortical gray matter. Among regional structures, AF/AFL was significantly associated with smaller hippocampal and amygdala volumes. At the hippocampal subfield level, reduced fimbria, dentate gyrus, CA1, and subiculum volumes were observed. Analyses based on self-reported history of AF did not demonstrate significant associations with any brain regions. In stratified analyses, participants aged <75 years showed a trend toward smaller hippocampal-tail volume with a significant interaction effect, whereas women exhibited smaller hippocampal volume without a significant sex interaction. Discussion: In this large community-based sample of cognitively normal older adults, AF/AFL was associated with widespread structural brain alterations and selective vulnerability in memory-related regions, including the hippocampus and amygdala, as well as specific hippocampal subfields. These findings suggest that AF/AFL may be associated with region-specific brain vulnerability before the onset of clinically apparent cognitive impairment.