Neurite orientation dispersion and density imaging (NODDI) and DTI-ALPS index reveal white matter microstructural abnormalities and glymphatic-like dysfunction linked to cognitive impairment in non-stroke atrial fibrillation patients.

BACKGROUND

While associations between silent white matter hyperintensities, diffuse microstructural damage, and cognitive impairment in atrial fibrillation (AF) patients without stroke have been reported, the precise underlying pathophysiological mechanisms remain to be fully elucidated. This study aimed to characterize white matter microstructure and glymphatic function in such patients using neurite orientation dispersion and density imaging (NODDI) and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. This study aimed to investigate alterations in white matter microstructure and glymphatic function in AF patients without stroke using NODDI.

METHODS

A total of 43 stroke-free AF patients and 53 healthy controls were enrolled. All participants underwent brain MRI on a 3.0 T scanner. Whole-brain white matter damage was assessed using diffusion metrics, while glymphatic function was evaluated via the DTI-ALPS index. Group differences in DTI and NODDI metrics were examined using two-sample t-tests. The associations between imaging measures and cognitive performance were analyzed using ordinal logistic regression and negative binomial regression, according to the data types of the respective cognitive tests. All models were adjusted for age, sex, and years of education.

RESULTS

No significant differences were observed in age (P = 0.869), sex (P = 0.054), or education level (P = 0.626) between the two groups. Significant alterations in DTI and NODDI metrics were identified in stroke-free AF patients. Compared with controls, AF patients exhibited significantly lower fractional anisotropy (FA) (PFWE < 0.05), neurite density index (NDI) (PFWE < 0.001), and orientation dispersion index (ODI) (PFWE < 0.001), alongside higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) (all PFWE < 0.001). Furthermore, the DTI-ALPS index was significantly lower in the AF group than in the control group (mean: 1.41 vs. 1.58, PFDR = 0.007). Multivariate regression analysis revealed that the NODDI-derived NDI and ODI were significantly associated with performance across all cognitive domains (all P < 0.01), establishing them as the most consistent predictors of cognitive function. In contrast, although the DTI-ALPS index was significantly reduced in the AF group (P < 0.05), it did not show a significant correlation with cognitive test scores.

CONCLUSIONS

This study confirms that white matter neurite microstructural damage is closely associated with decline across multiple cognitive domains in stroke-free AF patients, whereas glymphatic system dysfunction appears to play a more limited role in cognitive impairment in this population. The NODDI technique shows promise as an imaging biomarker for elucidating the microstructural underpinnings of AF-related cognitive impairment.