Pattern of Brain Parenchymal Damage Related to Glymphatic System Dysfunction: Longitudinal Evidence from a Community-based Cohort
Chengqian Li1, Wenxin Li1, Zi-Yue Liu1, Fei-Fei Zhai1, Fei Han1, Lixin Zhou1, Jun Ni1, Ming Yao1, Yi-Cheng Zhu1
1Department of Neurology, Peking Union Medical College Hospital
Objective:
This study aims to investigate the temporal and spatial patterns of structural brain injury related to the diffusion along the perivascular space (ALPS) index in a community-based population.
Background:
Previous studies reported that glymphatic system dysfunction was associated with brain parenchymal injury, while the injury patterns remain uncovered.
Design/Methods:
As part of a community-based cohort, we assessed diffusion tensor maps and vertex-wise cortex maps at both baseline and follow-up using FSL and FreeSurfer software. The statistical analysis of global measurements and voxel/vertex-wise analysis were performed to explore the relationship between lower ALPS index and brain parenchymal injury, including white matter microstructural integrity disruption and regional brain atrophy. Structural network parameters were calculated based on diffusion tensor imaging.
Results:
A total of 1120 participants were included in the baseline analysis, of whom 682 completed the follow-up brain MRI (age 55.02±7.98 years, 33% men, mean interval 5.52±0.48 years). A lower baseline ALPS index was strongly correlated with reduced FA and increased MD, AD, RD in multiple regions during follow-up, including the corpus callosum, right external capsule, right posterior thalamic radiation, left inferior and superior longitudinal fasciculus and bilateral inferior fronto-occipital fasciculus (threshold-free cluster enhancement corrected P<0.05, adjusted for age and sex). Also, participants with lower ALPS index showed greater cortical atrophy in the baseline analysis, primarily involving clusters in the frontal, temporal lobes and insula (Bonferroni-corrected with Monte Carlo simulation for cluster p-value <0.05 and adjusted for total intracranial volume). However, no significant correlation between ALPS index and cortical atrophy was observed in the longitudinal analysis. Additionally, A lower ALPS index was related to sub-network dysconnectivity in the frontal and parietal lobes.
Conclusions:
Our results demonstrated the dynamic pattern of brain parenchymal injury related to glymphatic system dysfunction, shedding light on the spatial pattern of white matter microstructural integrity disruption in community-dwelling populations.
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