Fatigue in Parkinson's disease and potential interventions

Fatigue is common in patients with Parkinson's disease (PD). It occurs at every stage of PD and affects quality of life. Fatigue severity worsens over time as PD progresses, and it is associated with other non-motor symptoms such as apathy, depression, sleep disorder, and cognitive dysfunction.

In this literature review, I discuss the measurement and pathophysiology of fatigue and fatigability. There are no evidence-based treatments for fatigue and fatigability available. I review several pilot studies on the effects of pharmacological agents and exercise on fatigue and fatigability. These studies provide some insights on the design of future larger clinical trials.

Fatigue inventories including The Fatigue Severity Scale, the Multidimensional Fatigue Inventory, or theParkinson Fatigue Scale are used to assess the severity of fatigue. Finger tapping and force generation are useful in quantifying physical fatigability. A reaction time paradigm such as the Attention Network Test can be used to measure cognitive fatigability. Physical fatigability is associated with the change in cortical excitability in PD measured by Transcranial Magnetic Stimulation. Cognitive fatigability is most likely associated with the neurotransmitter abnormalities (dopaminergic, cholinergic and noradrenergic) in PD. Levodopa, modafanil, methylphenidate, and rasagiline may be effective in treating fatigue and fatigability. Exercise programs may also be effective.