Abstract
BACKGROUND: Cognitive impairment associated with mild-to-moderate chronic traumatic brain injury (TBI) presents substantial challenges for which the functionality of the brain glymphatic system is a key area of interest. This study aimed to explore the functionality of the brain glymphatic system in patients with chronic cognitive impairment following mild-to-moderate TBI using diffusion tensor image analysis along the perivascular space (DTI-ALPS). METHODS: This was a prospective cross-sectional study. A total of 56 patients with mild-to-moderate chronic TBI at the Radiology Outpatient Clinic of the First Affiliated Hospital of Hainan Medical University were enrolled in the study between January 2021 and July 2022. Additionally, 20 healthy control (HC) subjects were recruited from the Health Screening Center during the same period as the HC group. Relevant clinical data for all the participants were collected, and cognitive assessments were conducted using cognitive scales. The TBI patients were categorized into the traumatic brain injury cognitive impairment (TBI-CI) and traumatic brain injury cognitively normal (TBI-CN) groups based on their of the Chinese Version of the Montreal Cognitive Assessment-Basic (MoCA-BC) scores. Each group comprised 20 subjects. All three groups of participants underwent diffusion tensor imaging (DTI). The DTI data were processed and analyzed using the MRIcron and FMRIB Software Library (FSL) toolboxes, and the analysis along the perivascular space (ALPS) index was calculated. Differences in the ALPS index among the three groups were examined by an analysis of covariance, adjusted for age and gender. A corrected receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of the ALPS index in identifying patients with traumatic chronic cognitive impairment. RESULTS: Compared with the HC group, both the mild-to-moderate TBI patients with and without cognitive impairment had a decreased ALPS index (HC vs. TBI-CI: 1.629 vs. 1.302, P<0.001; HC vs. TBI-CN: 1.629 vs. 1.523, P=0.003). Moreover, the decrease in the ALPS index was more significant in the mild-to-moderate TBI patients with cognitive impairment (TBI-CN vs. TBI-CI: 1.523 vs. 1.302, P<0.001). The adjusted ROC curve analysis revealed that the area under the curve (AUC) of the ALPS index for diagnosing traumatic chronic cognitive impairment was 0.983 [95% confidence interval (CI): 0.953-1, P<0.001], with a sensitivity of 90% and specificity of 95%. CONCLUSIONS: Cognitive impairment in patients with mild-to-moderate chronic TBI may be associated with impairment of the glymphatic system. Additionally, the ALPS index may serve as a potential predictor of the disease. Our findings provide some novel insights into the pathophysiological mechanisms underlying cognitive impairment in mild-to-moderate chronic TBI.