Association of free-water imaging data for the cholinergic nucleus with the motor function and subtypes in Parkinson's disease

Shanhu Xu ¹ Xiaoli Si ² Miao Cai ¹ Fengli Fu ³ Jun Tian ² Baorong Zhang ^2* Xiaoli Liu ^1*

• ¹ Department of Neurology, Affiliated Zhejiang Hospital Zhejiang University School of Medicine, Hangzhou, Jiangsu Province, China
• ² Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
• ³ Department of radiology, Affiliated Zhejiang Hospital Zhejiang University School of Medicine, Hangzhou, Jiangsu Province, China

Background: Despite the importance of clinical heterogeneity in Parkinson disease (PD), its underlying pathophysiology remains unclear.Objective: This study aimed to distinguish the association of free-water (FW) imaging data for the cholinergic nuclei with the motor subtypes of PD.The study included 150 cases of idiopathic PD from the Parkinson's Progression Markers Initiative cohort. FW imaging, including FW-corrected diffusion tensor imaging, was used to extract structural metrics from cholinergic nucleus 4 (Ch4) in the basal forebrain and the pedunculopontine nucleus. The motor subtypes were classified as tremor-dominant (TD, n = 99) and non-tremor-dominant (non-TD, n = 51). Statistical analyses were performed at baseline and the 4-year follow-up.Results: At baseline, FW-corrected mean diffusivity in Ch4 (MD-t-Ch4) was correlated with the tremor subscore, while FW-corrected fractional anisotropy in Ch4 (FA-t-Ch4) was negatively correlated with the rigidity subscore. However, the TD and non-TD groups showed no differences in cholinergic FW imaging data. Among the 84 patients who were followed-up, 36.36% (20/55) in the TD group and 25.64% (10/39) in the non-TD group showed a subtype shift after 4 years. Multivariate binary logistic regression analysis showed that the normalized FW value for Ch4 (nFW-Ch4) was a predictor of subtype at the 4-year follow-up (P = 0.041). In the TD subgroup, both nFW-Ch4 (P = 0.015) and normalized MD-t-Ch4 (P = 0.013) predicted subtype stability. The area under the receiver operating characteristic curve values were 0.69 and 0.73, respectively. Conclusions: Tremor and rigidity subscores were correlated with Ch4 FW imaging data.Moreover, Ch4 FW imaging predicted the motor subtype at the 4-year follow-up, especially identifying potential postural instability and gait difficulty (PIGD) subtype converters from the TD group.