Parkinson's Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

J Clin Neurol. 2016 Apr;12(2):172-80. doi: 10.3988/jcn.2016.12.2.172. Epub 2016 Feb 4.

Abstract

Background and purpose: The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue.

Methods: PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins-α-synuclein oligomer, β-amyloid (Aβ)₁₋₄₂, and tau-were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients.

Results: The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ₁₋₄₂ was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders.

Conclusions: PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF.

Keywords: Parkinson's disease; cerebrospinal fluid; fatigue; motor symptoms; nonmotor symptoms; α-synuclein oligomer.