Association of diffusion along the perivascular spaces with clinical symptoms and dopaminergic degeneration in Parkinson’s disease

This study aimed to investigate the association between the diffusion tensor image (DTI) analysis along the perivascular space (ALPS) index, striatal dopamine transporter (DAT) availability, and baseline motor and cognitive function in 207 patients with newly diagnosed Parkinson’s disease (PD). All patients underwent brain MRI and 18F-FP-CIT PET scans, and ALPS index was calculated to assess glymphatic system function. Multiple linear regression analyses demonstrated that ALPS index and DAT availability in the posterior putamen were negatively associated with the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores.

Mediation analyses showed that ALPS index affected UPDRS-III scores both directly (β = −10.116, P = 0.002) and indirectly via DAT availability in the posterior putamen (β = 2.509, P = 0.036). Furthermore, ALPS index and DAT availability in the associative striatum were positively associated with the Mini-Mental State Examination (MMSE) scores. The ALPS index affected MMSE scores both directly (β = 1.317, P = 0.003) and indirectly via DAT availability in the anterior putamen (β = −0.169, P = 0.047).

The relationship between ALPS index and baseline motor or cognitive function was significant only when striatal dopamine was severely depleted. These findings suggest that glymphatic dysfunction is associated with worse motor and cognitive function in PD and may exert stronger effects when striatal dopamine is severely depleted. This research was supported by grants from the Central Medical Service (CMS) Co., Ltd.

This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2023-KH-134527 and RS-2023-00266948). The authors received no specific funding for this work. These authors contributed equally: Chae Jung Park, Kyunghwa Han.

Department of Radiology, Research Institute of Radiological Science, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Sciences, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea Chae Jung Park, Kyunghwa Han, Jun Hwee Kim & Seung-Koo Lee Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA MR Clinical Science, Philips Healthcare Korea, Seoul, Republic of Korea Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea Han Kyu Na, Phil Hyu Lee, Yun Joong Kim, Young H. Sohn & Seok Jong Chung Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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