Physical and mental fatigue in Parkinson's disease: epidemiology, pathophysiology and treatment.

Fatigue is one of the most common non-motor complaints of Parkinson's disease (PD) patients and is associated with reduced activity and poorer quality of life. Fatigue can be experienced as a state of being tired or weary (subjective fatigue) or as a process of becoming tired or fatigued (fatigability). Subjective mental and physical fatigue are evaluated using self-report questionnaires such as the Multidimensional Fatigue Inventory. Physical fatigability is studied in a laboratory setting using physical exercise protocols and transcranial magnetic stimulation. Mental fatigability is evaluated by measuring attention over time using a reaction-time paradigm called the Attention Network Test (ANT). PD patients report more subjective physical and mental fatigue than controls on a variety of fatigue questionnaires. PD patients have increased physical fatigability in force generation and finger tapping. Levodopa and modafinil improve physical fatigability in PD subjects. Methylphenidate is useful for treating subjective physical fatigue. PD subjects have greater mental fatigability than control subjects and display abnormal performance in all three attention networks in the ANT. Therapies targeting the neurotransmitter systems involved in attention may be helpful for treating mental fatigability. Future fatigue research should focus on developing gold standards for fatigue measurement and developing treatments for fatigue and fatigability in PD.