Fatigue: The Silent Symptom of Parkinson’s Disease

A 2013 survey by the Parkinson’s disease Foundation (PDF) identified fatigue as the most pressing need for the Parkinson’s research community.

While tremors, muscle stiffness, and irregular gait are the symptoms most associated with Parkinson’s disease, 50% of PD patients experience severe fatigue and a third say it is their single most debilitating symptom. Fatigue is the most significant reason cited for medical disability insurance claims by PD patients in the United States. Despite this overwhelming evidence, neurologists tend not to recognize fatigue as a prominent concern of PD patients.

Two studies in newly diagnosed Parkinson’s patients reported fatigue to be a clinically relevant problem even when motor symptoms were minimal. These studies identified fatigue as a “pre-motor” symptom, appearing well before motor symptoms become obvious. Parkinson’s patients describe their fatigue as different than any tiredness they had experienced before their diagnosis. Unlike fatigue in the general public, PD fatigue often improves with exercise.

Mental fatigue that affects Parkinson’s patients is called “central fatigue” and relates to the experience of feeling weary or exhausted during an intellectually challenging task, along with decreased capacity to initiate or sustain cognitively challenging activities. Parkinson’s patients suffering from cognitive fatigue have reduced attention span, and may have deficits in learning, memory, and information processing. Cognitive fatigue will often emerge as tasks become increasingly more complex or attention demands are greater.

Causes of PD Fatigue

The cause of fatigue in Parkinson’s disease is still elusive, though researchers speculate it may be due to changes that take place in the brain. Recently, researchers have found that Parkinson’s patients with fatigue had significantly lower serotonin transporter binding than patients without fatigue in the basal ganglia and limbic structures of the brain. Other causes of PD fatigue under investigation include peripheral inflammation and immune activation, and mitochondrial dysfunction.

Depression, sleep disturbances, and medications may also contribute to or cause fatigue. However, Dr. Joseph Friedman, Professor and Chief of the Division of Movement Disorders at the Warren Alpert Medical School of Brown University, points out that while fatigue is an early symptom and may be associated with depression, most PD patients with fatigue are not depressed.

Clinicians and researchers use rating scales for diagnosing the existence and severity of PD fatigue. Some scales, such as the Modified Fatigue Impact Scale, evaluate cognitive, as well as physical and social function. While most of these tests evaluate fatigue on a subjective level, objective measures for cognitive function exist that can measure performance changes during mental tasks.

Treatment Approaches

Currently, there are no effective treatments for PD fatigue. Clinicians often encourage patients to exercise, practice good sleep habits, take naps, keep mentally active, increase the intake of fiber and drink plenty of water. 

While few medications have proven to be helpful, methylphenidate, a pharmaceutical stimulant, was shown to be effective in lowering fatigue scores in patients with PD in a 6-week treatment period. This medication is often prescribed off label in clinical practice to help combat the effect of debilitating fatigue in PD patients.

In order to offer better treatment options, clear standards to measure and define fatigue in Parkinson’s disease are necessary. Research is also needed to identify biomarkers that can better diagnose and evaluate fatigue treatments. Using a range of brain imaging techniques to examine the underlying biology of fatigue, including the role of inflammation, could help identify changes in the brain associated with fatigue. Lastly, studying the effectiveness of non-drug therapies such as mindfulness-based stress reduction and energy management strategies (pacing), may be helpful. These non-drug therapies have been shown to also be helpful to patients with fatigue due to Multiple Sclerosis.

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