Cerebral metabolism mediates cognitive impairment in stroke-free atrial fibrillation patients: a mediation analysis...

Atrial fibrillation, one of the most common types of arrhythmia, is a major risk factor for stroke. Previous studies have demonstrated cognitive decline in atrial fibrillation patients regardless of stroke comorbidity. This study aimed to investigate the relationship between cerebral metabolic alterations and cognitive impairment in stroke-free atrial fibrillation patients.

In the retrospective cohort study, we enrolled 68 stroke-free atrial fibrillation patients and 68 age-matched sinus rhythm controls who underwent 18F-fluorodeoxyglucose PET-computed tomography imaging between 1 January 2018 and 31 December 2022 in the third Affiliated Hospital of Soochow University. Regional cerebral metabolism was assessed using DPABI software, with the standardized uptake value ratio (SUVR) of regions of interest calculated as the average standardized uptake value (SUV mean ) of specific brain regions divided by the average SUV of the cerebellum. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE). The MMSE has a total score of 30 points, with scores <24 indicating cognitive impairment. Clinical data, electrocardiograms, echocardiograms, and other relevant information were systematically collected. Correlation analyses were performed to investigate the association between metabolic changes and cognitive impairment.

Cognitive assessment using the MMSE revealed significantly lower scores in atrial fibrillation patients compared to control [25.00 (24.00-26.00) vs. 27.00 (25.00-28.00), P  < 0.001] and the prevalence of cognitive impairment was significantly higher in the atrial fibrillation group than in the control group (17.64% vs. 4.41%, P  = 0.012). Regional cerebral metabolic analysis demonstrated widespread SUVR reductions in atrial fibrillation patients across multiple cognition-related regions, including the frontal, temporal, parietal, and occipital lobes, cingulate gyrus, thalamus, basal ganglia, and cerebellum. Multivariable logistic regression identified significant inverse associations between elevated SUVR values and cognitive impairment in the right calcarine fissure and surrounding cortex (Calcarine_R: adjusted OR = 0.004, P  = 0.033), bilateral lingual gyrus (Lingual_L/R: adjusted OR = 0.002, P  < 0.04), and Lobule VI-VIII of vermis (Vermis_6/7: adjusted OR = 0.000, P  < 0.035). Mediation analysis confirmed these regions as significant pathways linking atrial fibrillation to cognitive dysfunction, with Calcarine_R showing the strongest mediation effect (proportion: 40.80% crude, 36.30% adjusted; all P  < 0.05).

These findings suggest that stroke-free atrial fibrillation patients exhibit abnormal cerebral metabolic patterns in specific brain regions, and some of the abnormal cerebral metabolic activities are closely linked to cognitive decline. These metabolic alterations may serve as potential neurobiological markers for predicting cognitive impairment in stroke-free atrial fibrillation patients.