Distinct Changes in Global Brain Synchronization in Early-Onset vs. Late-Onset Parkinson Disease.

Tianyu Wang,Qin Shen,Sainan Cai,Changlian Tan,Lin Zhang,Min Wang,Haiyan Liao,Junli Li,Yuheng Zi,Zhenni Mao,Yijuan Xiang

doi:10.3389/fnagi.2020.604995

Abstract

Early- and late-onset Parkinson’s disease (EOPD and LOPD, respectively) have different risk factors, clinical features, and disease course; however, the functional outcome of these differences have not been well characterized. This study investigated differences in global brain synchronization changes and their clinical significance in EOPD and LOPD patients. Patients with idiopathic PD including 25 EOPD and 24 LOPD patients, and age- and sex-matched healthy control (HC) subjects including 27 younger and 26 older controls (YCs and OCs, respectively) were enrolled. Voxel-based degree centrality (DC) was calculated as a measure of global synchronization and compared between PD patients and HC groups matched in terms of disease onset and severity. DC was decreased in bilateral Rolandic operculum and left insula and increased in the left superior frontal gyrus (SFG) and precuneus of EOPD patients compared to YCs. DC was decreased in the right putamen, mid-cingulate cortex, bilateral Rolandic operculum, and left insula and increased in the right cerebellum-crus1 of LOPD patients compared to OCs. Correlation analyses showed that DC in the right cerebellum-crus1 was inversely associated with the Hamilton Depression Scale (HDS) score in LOPD patients. Thus, EOPD and LOPD patients show distinct alterations in global synchronization relative to HCs. Furthermore, our results suggest that the left SFG and right cerebellum-crus1 play important roles in the compensation for corticostriatal–thalamocortical loop injury in EOPD and LOPD patients, whereas the cerebellum is a key hub in the neural mechanisms underlying LOPD with depression. These findings provide new insight into the clinical heterogeneity of the two PD subtypes.

Highlights

Idiopathic Parkinson’s disease (PD) can be subdivided into early- and late-onset forms (EOPD and LOPD, respectively) according to the age of onset
The Hamilton Depression Scale (HDS) scores of EOPD and LOPD patients were higher than those of the respective age-matched control groups (p ≤ 0.001), whereas no significant differences were observed in terms of age, sex, education level, Daily Levodopa Equivalents Dose (DLED), and Mini-Mental State Examination (MMSE) score
degree centrality (DC) was increased in the left superior frontal gyrus (SFG), precuneus, and decreased in bilateral Rolandic operculum and left insula of EOPD patients compared to younger controls (YCs) subjects (Figure 1)

Summary

Introduction

Idiopathic Parkinson’s disease (PD) can be subdivided into early- and late-onset forms (EOPD and LOPD, respectively) according to the age of onset (before or after 50 years, respectively; Schrag and Schott, 2006; Marras and Lang, 2013). Genetic factors have a greater influence on the occurrence of EOPD compared to LOPD, with first-degree relatives of EOPD patients more frequently exhibiting nonmotor symptoms and being at higher risk of developing PD (Stern et al, 1991; Liu et al, 2018). Histopathologic and molecular analyses have revealed a greater loss of dopaminergic neurons in the substantia nigra and damage to the dopaminergic system in EOPD patients (Mayer et al, 1986; Shih et al, 2007). These findings suggest that distinct neuropathophysiologic mechanisms underlie EOPD and LOPD

Methods

Results

Conclusion