Towards an understanding of fatigue in Parkinson’s disease

Abstract

Objectives: To gain an improved understanding of fatigue in Parkinson's disease (PD) by exploring possible predictors among a wide range of motor and non-motor aspects of PD.

Methods: 118 consecutive PD patients (54% men; mean age, 64 years) were assessed regarding fatigue, demographics and a range of non-motor and motor symptoms. Variables significantly associated with fatigue scores in bivariate analyses were used in multiple regression analyses with fatigue as the dependent variable.

Results: Fatigue was associated with increasing Hoehn & Yahr stages, specifically transition from stages I-II to stages III-V. Regression analysis identified five significant independent variables explaining 48% of the variance in fatigue scores: anxiety, depression, lack of motivation, Unified PD Rating Scale (UPDRS) motor score and pain. Gender, age, body mass index, PD duration, motor fluctuations, dyskinesias, symptomatic orthostatism, thought disorder, cognition, drug treatment, sleep quality and daytime sleepiness were not significantly associated with fatigue scores. When considering individual motor symptom clusters instead of the UPDRS motor score, only axial/postural/gait impairment was associated with fatigue.

Conclusions: We found fatigue to be primarily associated with symptoms of depression and anxiety, and with compromised motivation, parkinsonism (particularly axial/postural/gait impairment) and pain. These results are in agreement with findings in other disorders and imply that fatigue should be considered a separate PD entity differing from, e.g., excessive daytime sleepiness. Fatigue may have a distinguished neurobiological background, possibly related to neuroinflammatory mechanisms. This implies that novel treatment options, including anti-inflammatory therapies, could be effective.