Assessment of the glymphatic dysfunction in amyotrophic lateral sclerosis using the diffusion tensor imaging along the perivascular spaces index: a pilot study

Seol-Hee Baek¹Woo-Suk Tae^2*Jin-Woo Park¹Byung-Jo Kim^1,2*

• ¹Department of Neurology, Korea University Anam Hospital, Seoul, Republic of Korea
• ²Brain Convergence Research Center, Korea University Medical Center, Seoul, Republic of Korea

Background: The glymphatic system plays a critical role in clearing interstitial waste from the brain. Dysfunction of this system has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Diffusion tensor imaging along the perivascular spaces (DTI-ALPS) index has emerged as a potential neuroimaging biomarker for evaluating glymphatic function. This study investigates whether glymphatic function in ALS differs from that in Parkinson's disease (PD), and normal controls (NCs) using the DTI-ALPS index. Methods: This study included 35 ALS patients, 35 age-and sex-matched PD patients, and 13 NCs. Diffusion tensor imaging was conducted, and the DTI-ALPS index was calculated. Clinical assessments included demographic data, disease duration, cognitive status, and functional scales. Group comparisons and correlation analyses were performed to assess the relationship between DTI-ALPS index and clinical parameters. Results: The ALS groupexhibited a significantly lower right-side DTI-ALPS index compared to NCs (p=0.037), while no differences were observed between ALS and PD groups. The DTI-ALPS index negatively correlated with age in ALS and PD groups but showed no correlation with clinical measures in ALS. Women in the ALS group had a significantly higher DTI-ALPS index compared to men. Conclusion: Glymphatic dysfunction may contribute to ALS pathogenesis, as evidenced by a reduced DTI-ALPS index compared to NCs. However, its clinical relevance and specificity for ALS remain uncertain. Further studies with larger cohorts are warranted to validate these findings.