Introduction
Jau-Shin Lou, MD, PhD, MBA
Fatigue is one of the most common non-motor symptoms reported in Parkinson’s disease (PD). Up to 58% of patients with PD report symptoms of fatigue, and a third of patients claim it is their most disabling symptom. Fatigue impacts the quality of life of patients by interfering with hobbies and occupations. A 2007 report on Social Security Disability claims in the United States identified that among patients with PD approved for work disability, fatigue was the primary complaint. However, it is very challenging to define a threshold at which normal fatigue becomes pathological fatigue. Four experts who are members of an international workgroup on fatigue in PD answer several important questions in this topic.
How is the fatigue in PD compared to fatigue in other disorders?
Joseph Friedman, MD
There have not been any studies directly comparing scores on the questionnaires assessing fatigue in PD versus other disorders. To date, there have been no specific findings that discriminate “PD fatigue” from fatigue due to other conditions. It will be very difficult to isolate a distinct profile since there are many disorders that are associated with fatigue, and PD patients often have one or more of them. For example, fatigue is associated with depression, apathy and anxiety, and all three, often in combination with each other, are common in PD. Furthermore, fatigue is associated with most medical disorders, such as heart failure, diabetes, arthritis, anemia and PD patients, being older, often have one or more of them. Sleep disorders affect over 75% of PD patients, which is frequently either co-existent with fatigue, or complicates assessment of it. Determining whether a specific “PD fatigue” exists will require detailed assessments of PD patients who have no other problems that contribute to their fatigue and then comparing these assessments to PD patients with other contributing disorders, as well as to non-PD patients who suffer from fatigue. Hopefully a biomarker of fatigue may be found that will obviate the need for questionnaire assessments. This is not likely to occur soon.
If fatigue is so common in patients with PD, how do we decide if fatigue is affecting patients’ quality of life?
Benzi Kluger, MD
One of the tricky things about studying fatigue is that the term “fatigue” is a commonly used word and needs to be precisely defined to conduct meaningful research and to help patients. Fatigue can be defined as a sense of increased effort with activity, which can be a normal reaction to any prolonged or difficult activity. What we are interested in for PD patients is abnormal fatigue that limits activity and affects a person’s quality of life.
We recently published a paper defining PD-related fatigue emphasizing the importance of: 1) Distinguishing fatigue from potentially similar symptoms like sleepiness or depression; 2) Making sure that fatigue is not caused by other problems, particularly something that could be treatable such as anemia, low blood pressure or medications; and 3) Determining whether the fatigue a person is experiencing is truly disabling.
There are many ways that PD-related fatigue may affect someone’s quality of life including:
- Interfering with the ability to complete activities. For example, not being able to work on a task for more than 15 minutes at a time.
- Leading a person to avoid activities because they know the activity will be overwhelming or lead to exhaustion. These could be physical, social or mental activities.
- Leading a person to avoid prolonged work because it can reduce their energy for the next few days.
- Taking away enjoyment from activities because of uncomfortable feelings of fatigue that they have to fight through.
- Having difficulty planning their day because of the possibility of experiencing severe fatigue at any time.
- Having to plan their day around fatigue, considering that they will need a nap most commonly early afternoon.
- Fatigue may have adverse effects on mood and may interfere with self-care activities such as exercise.
- Patients may feel embarrassed about fatigue or feel that people are judging them for being lazy.
We think it is important for doctors and researchers to understand how fatigue affects quality of life so that we can provide better education to patients and family. Clearly, we can also advocate for PD patients affected by fatigue by working on developing more effective therapies.
Are there any biomarkers for fatigue in PD?
Kelvin Chou, MD
Unfortunately, there are no definitive biomarkers for PD-related fatigue. Part of the problem is the lack of a precise definition for PD-related fatigue in the past. Several small studies have been published investigating either inflammatory markers in serum or cerebrospinal fluid (CSF) or imaging biomarkers. Fatigue in PD has been associated with elevated CSF C-reactive protein levels, higher serum levels of interleukin-6 (IL-6), reduced serotonin transporter uptake on PET and decreased uptake using 131I-MIBG myocardial scintigraphy. However, these associations need to be confirmed in larger studies.
Are there any effective treatments for fatigue in PD?
Jau-Shin Lou, MD, PhD, MBA
There have been no evidence-based treatments for fatigue in PD. Several small pharmacological studies have shown that levodopa/carbidopa, modafinil, methylphenidate, or rasagiline might be effective in treating fatigue in PD.
Exercise may be effective in reducing fatigue and fatigability. It is common knowledge that exercise is beneficial for general health, including improving cardiovascular and pulmonary function, reducing osteoporosis and sarcopenia associated with aging, and improving psychological status. A small, but well-designed and well-executed study demonstrated that high-intensity individualized exercise improved fatigue and fatigability and was associated with an increase in muscle mass, mitochondrial function, and physical capacity in patients with Parkinson's disease.
Regardless of the type of exercise program employed, compliance will be a key factor in determining program effectiveness in improving fatigue and fatigability. Programs such as home treadmill or community walking will likely have a higher compliance rates. In contrast, programs that require coaching or going to a gym (thus involving more barriers to exercise such as cost and scheduling conflicts) will likely have a lower compliance rate.