Free water imaging reveals asynchronous dopaminergic degeneration in substantia nigra and ventral tegmental area in prodromal and early Parkinson's disease

Abstract

Purpose: The ventral tegmental area (VTA), which is rich in dopaminergic neurons, may play a role in influencing clinical symptoms in Parkinson's Disease (PD). However, the degeneration dynamics of the VTA during the early and prodromal stages of PD remain unclear. This study aims to explore microstructural changes in the VTA among prodromal PD patients with idiopathic REM sleep behavior disorder (iRBD) and early-stage PD patients using free water imaging (FWI) to assess free water (FW) and its correlation with clinical symptoms.

Method: Diffusion tensor imaging data from 238 participants, including 69 healthy controls (HC), 54 iRBD patients, and 115 PD patients. FW values were computed using a bi-tensor model, and comparisons were done between the HC, iRBD, and PD groups. Additionally, the relationship between FW values in the VTA and substantia nigra pars compacta (SNc) and clinical symptoms was explored through baseline assessments and longitudinal tracking of iRBD patients.

Results: FW values in the SNc significantly increased in iRBD and PD patients compared to HC, with the PD group exhibiting even higher FW values. Initially, the FW values in the VTA in iRBD patients did not significantly differ from those of HC but increased in early PD, correlating with anxiety and motor deficits. Longitudinal tracking revealed FW increases in the SNc and VTA in iRBD patients over time.

Conclusion: The present findings revealed a desynchronized degeneration pattern between the VTA and SNc, with no degeneration observed in the prodromal phase but gradual changes over time, leading to pronounced VTA degeneration in early PD. This underscores the impact of early VTA changes on PD symptoms, contributing to understanding of PD pathophysiology.

Keywords: Free water imaging; Idiopathic REM sleep behavior disorder; Parkinson’s disease; Substantia nigra pars compacta; Ventral tegmental area.