Treatment Of Fatigue In Parkinson’s Disease

What Causes Fatigue In Parkinson’s

The precise mechanisms that cause fatigue are unclear but research suggests that any neurological disorder which involves the basal ganglia area of the brain is likely to be associated with significant fatigue. This includes Parkinsons.

In some cases Parkinsons medication may be a factor, for example dopaminergic medications may affect sleep and so add to fatigue. Dosage and timing of medication may also affect energy levels.

Fatigue may be linked to other Parkinsons symptoms, for example depression. With depression there is usually also fatigue, as well as loss of motivation, a general lack of interest and difficulty in sleeping. It is important that these symptoms are recognised as they are very treatable, and overcoming them can reduce fatigue.

If you experience tremor, rigidity or dyskinesia your muscles will have to work harder in order to carry out simple movements or tasks which can mean muscles fatigue more quickly and easily. Slowness of movement may also increase fatigue by making activities and tasks more prolonged and effortful.

You may have sleep problems and poor quality sleep tends to lead to excessive day-time sleepiness and a tendency to nap. Although sleepiness is a separate symptom to fatigue, it clearly adds to the problem and fatigue is hard to overcome if you are sleepy.

Treatment For Fatigue In Parkinson’s Disease

At least one-third of people with Parkinson’s disease complain about fatigue. It is unclear what treatment is best to reduce fatigue in people with Parkinson’s disease.

We reviewed the medical literature up to April 2015, and found 11 studies that included a total of 1817 people. Nine studies investigated the effects of medication on fatigue. Two studies investigated the effects of exercise on fatigue. We found no studies that investigated the effect of cognitive-behavioural therapy.

We found that doxepin , a drug to treat depression, may reduce fatigue. We found that rasagiline , an anti-Parkinson drug, reduced or slowed down the progression of physical fatigue. Most drugs were safe however, levodopa-carbidopa may cause nausea.

We found no evidence that exercise reduces fatigue in Parkinson’s disease.

Based on the current evidence, it is not clear what treatment is most effective to treat fatigue in people with Parkinson’s disease. Future studies should investigate the effect of cognitive-behavioural therapy on fatigue in people with Parkinson’s disease.

Factors contributing to subjective fatigue in people with idiopathic Parkinsons disease are not well known. This makes it difficult to manage fatigue effectively in PD.

To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD.

Association Between Fatigue And Quality Of Life In Parkinsons Disease

To determine the relationship between the perception of fatigue and quality of life, a canonical correlation analysis was conducted using the fatigue scales as the criterion variables and quality of life measures as the predictor variables. The range of correlation within the fatigue scales was r=0.86 to 0.85 and r=0.74 to 0.82 among the quality of life variables. The highest correlated predictor variables was between the PDQ-39SI and NMSQ measures. Omission of either variable did not change the results these two variables were therefore retained. The multivariate analyses produced four discriminant functions, of which the first was significant, F=13.24, p=0.0005 based on Roys greatest-root test. The correlation between the two sets of variables was Rc=0.98, indicating a high degree of relationship between the predictor and criterion variables. The squared canonical correlation which represented the proportion of the variance in the canonical variate of the fatigue scales that can be explained by the canonical variate of the quality of life variables was 96%.

Table 1 Canonical loadings for the fatigue and quality of life in the Parkinson group

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Treating Fatigue In Parkinsons Disease

There are currently few treatments available that directly alleviate fatigue, which can make it difficult to treat. However, people with PD who experience fatigue should talk to their doctor as changes in their current medications may help relieve fatigue. Complementary therapies, such as acupuncture or massage, may help improve symptoms of fatigue. In addition, there are several lifestyle approaches that can help manage fatigue, including:

Triggers And Alleviating Factors For Fatigue In Parkinsons Disease

• Roles Conceptualization, Data curation, Formal analysis, Writing original draft, Writing review & editing

  Affiliation Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States of America

• Roles Conceptualization, Data curation, Formal analysis, Writing review & editing

  Affiliation Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States of America

• Roles Conceptualization, Writing review & editing

  Affiliation Department of Neurology, Duke University, Durham, NC, United States of America

• Roles Conceptualization, Writing review & editing

  Affiliation Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States of America

• Roles Conceptualization, Project administration, Writing review & editing

  Affiliation Columbia University School of Social Work, New York, NY, United States of America

• Roles Conceptualization, Funding acquisition, Project administration, Writing review & editing

  Affiliation The Michael J. Fox Foundation for Parkinsons Research, New York, NY, United States of America

• Roles Conceptualization, Writing review & editing

  Affiliation Department of Neurology, University of Toronto, Toronto, Ontario, Canada

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Preparation For Model Building

Preprocessing consisted of removing incomplete records, duplicate records and records of control patients. Furthermore, only records from the first clinic visit were used, since most patients did not have data associated with subsequent visits and thus the sample size appeared inadequate for analysis. The remaining dataset of 182 PD patients records contained no redundant independent variables with a predominant single value. Patient demographics of the pre-screening and post-screening datasets were displayed in the results section.

Quality metrics to assess the validity of the results were accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, and these metrics are discussed in the results section.

Imaging Of Fatigue In Pd

Motor symptoms in PD result from nigrostriatal dopaminergic denervation, but dopaminergic dysfunction does not appear to be related to fatigue in PD. In the ELLDOPA cohort, 49 levodopa-naive PD patients with fatigue had similar –CIT striatal dopamine transporter uptake as 82 PD patients without fatigue. Another study showed no difference in 18F-dopa uptake between 10 fatigued PD subjects and 10 nonfatigued PD subjects.,

Serotonin transporter uptake has been reported to be reduced in chronic fatigue syndrome,, suggesting that nondopaminergic pathways may be involved in PD fatigue. Pavese et al. compared serotonergic transporter uptake ligand 11C-DASB) in seven PD subjects with fatigue and eight PD subjects without fatigue. Serotonin transporter binding in the caudate, putamen, ventral striatum, insula, and thalamus was decreased in the fatigued patients. The relationship of the cholinergic system to PD fatigue has not been investigated. The autonomic nervous system may also be involved in PD fatigue. One study found that pressor responses in norepinephrine and dobutamine infusion tests were greater and MIBG cardiac uptake was decreased in PD subjects with fatigue compared with those without fatigue.,

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Figuring Out Causes Of Fatigue

The first step in easing the fatigue associated with Parkinsons disease is to rule out other causes of tiredness, says Liana Rosenthal, M.D., assistant professor of neurology at the Johns Hopkins University School of Medicine and director of clinical core at the Morris K. Udall Center Parkinsons Disease Research Center of Excellence. We evaluate patients to see if there are other things contributing to the fatigue besides their disease, she says.

Sometimes patients may be referred to a sleep specialist for an evaluation. That can help identify causes of tiredness, like sleep apnea. Rosenthal says: Our aim is to first treat any sleep issues, like insomnia, sleep apnea or other causes of poor sleep. Once we treat and address those issues, we can see if fatigue still persists.

Fatigue In Parkinsons Disease And Potential Interventions

This abstract of a literature review discusses the measurement and pathophysiology of fatigue and fatigability. There rare no evidence-based treatments available. Several pilot studies are reviewed on the effects of pharmacological agents and exercise. These provide some insights on the design of future larger clinical trials. Fee for full article at IOS Press.

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Fatigue In Parkinsons Disease: Report From A Multidisciplinary Symposium

A summary of a symposium in October, 2014, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from other disorders in which fatigue figures prominently, and concluding with focused recommendations to enhance understanding and treatment of fatigue in Parkinsons disease.

Physiology And Biomarkers For Fatigue In Pd

The physiology underlying fatigue symptoms in PD is unknown, whereas much is known about the mechanisms of motor fatigability. The only published study of physiological differences between fatigued and nonfatigued PD patients found no measurable differences in oxygen utilization during exercise, but some studies have suggested that exercising improves fatigue.,,, Whether fatigue fluctuates with motor fluctuations was looked at in one study. Subjects were assessed during their off, whereas all other studies used the subjects experience over a preceding time interval of weeks. Eighty-eight percent of their subjects were fatigued, and fatigue increased with motor ”off.” Too few subjects were nonfatigued to determine how often fatigue occurred only during motor ”off.” The physiological implications are unclear, as many other nonmotor symptoms also increased during the ”off” period.

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Methylphenidate Use For Fatigue In Parkinsons

Methylphenidate , better known by its brand name, Ritalin, is popular for its use in the treatment of children with ADHD. It was FDA approved in the 1950s and became increasingly prescribed in the 1990s. MP has since been used for other disorders, including narcolepsy, refractory depression and fatigue caused by medical and neurological disorders.

Fatigue in Parkinsons is a common problem encountered by one-third to one-half of people with the disease. Parkinsons fatigue is often unrelated to the disease severity and overall motoric disability. Medications used to treat the motor symptoms of Parkinsons typically do not improve fatigue, and treatment specific to fatigue is lacking.

MP is a psychostimulant which has seen an increase in off-label use to treat Parkinsons fatigue. MP works by decreasing the reuptake of neurotransmitters, like dopamine and norepinephrine, thus making them available longer in the synaptic cleft where the chemicals can act on the receiving brain cells.

Based on their clinical experience, many physicians are recommending that patients try MP for Parkinsons fatigue, especially when quality of life is greatly impacted.

MP is an old drug that may have newer uses it may have potential to help people with Parkinsons. As with all medications, discuss the risks and benefits of MP with your neurologist and other healthcare team members before deciding if it is right for you.

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I am a very active person, but deep fatigue must be addressed with rest. Taking a day to rest is not in my nature. It makes me feel like a sloth. Yet, when deep fatigue hits me, the best remedy is to do just that take the day off! I limit myself to one day of physical rest, very rarely two days . I also find that the mind must rest with the body. Getting the mind to a quiet place is the practice of meditation, in whatever form suits the moment. At the height of deep fatigue, meditation can be very difficult, but not impossible. At times, it has taken me four hours to quiet my mind and body to get rejuvenating rest.

But there is a caution here: Be wary of using rest as an excuse to procrastinate. In another column, Ill address the link of scenario looping to set-shifting issues and difficulty initiating new tasks. Basically, getting off the sofa can be problematic if I stay there too long. Perhaps this seems contradictory to my history as a highly active person, but that is the nature of PDs nonmotor effects. Once off the sofa, I make myself shift into a physical task, followed by a short rest and then some type of mental task. There is always some resistance to overcome to do this to get off the sofa but the rest is absolutely necessary to stop the deep fatigue.

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Fatigue In Parkinsons Disease

Fatigue is a common but under-recognized problem for people with Parkinsons disease . Fatigue can be defined as an unpleasant sensation of lacking energy, making the performance of routine activities, physical or mental, a strain. People with PD may experience physical fatigue, mental fatigue, or both. Fatigue in PD is not the same as the feeling you might get at the end of a hard days work. It is not necessarily something that goes away with rest. When people with PD are asked about fatigue, they use phrases such as, I feel run down, I am out of energy, I am unable to do anything, I cant get motivated.

Fatigue in Parkinsons Brochure

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Fatigue is common in PD

Fatigue and Depression

There is a large overlap between fatigue and other problems in PD, especially depression and sleep disorders. People with fatigue are more likely to be depressed and people who are depressed are more likely to be fatigued, but there is nonetheless a large group of PD patients who are fatigued but not depressed. Depression in PD typically responds to antidepressant treatment, and depression-related fatigue may improve with such treatment.

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Fatigue and Sleep disorders

Causes of Fatigue

Building The Predictive Model

This project features three analytical approaches using random forest, Boruta and PCA. The methodology for each approach is discussed separately below. Furthermore, for transparency and reproducibility, the code used to perform the analyses can be found at .

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Causes Of Fatigue In Parkinsons Disease

Many of the symptoms of PD, including slow movement, muscle stiffness, depression, and changes to sleep quality can cause or worsen the symptom of fatigue.

• Akinesia Fatigue may be caused by akinesia . People experiencing akinesia find it challenging to accomplish simple tasks, requiring significantly more energy to get through the daily activities.
• Muscle fatigue Many of the symptoms of PD that affect the muscles, like stiffness, cramping, tremor, and difficulty starting movement, put extra stress on the muscles, causing fatigue. In addition, some people with PD experience muscle atrophy, in which the muscles shrink and weaken due to lack of use. Muscle atrophy decreases a persons stamina and endurance, contributing to the sense of fatigue.
• Depression Depression is another common non-motor symptom of PD, occurring in approximately 40% of people with PD. Depression can cause fatigue, adding to a sense of low energy or lack of motivation.
• Sleep disturbance PD often causes changes in sleep cycles, which can add to a sense of fatigue during the day.
• Medications Some of the medications used to treat PD, including dopamine agonists, can cause fatigue as a side effect. Others may cause insomnia as a side effect, leading to daytime fatigue.1,2

Coping With Fatigue In Pd

Fatigue can make motor symptoms, like tremors, seem like they are worst when they are not. Dr. De León has a list of eight things you can do to prevent or improve fatigue, If you still have severe fatigue discuss it with your physician because there are some medications which can help. The key is well adjusted medications, exercise, good nutrition, and rest at least 5 minutes every day.

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Pharmacologic Therapies For Excessive Daytime Sleepiness

If nonpharmacologic strategies do not improve EDS, drug therapies can be considered. There are few recommendations for the pharmacological management of EDS in PD, as few multicenter clinical trials have been conducted in this area. A Movement Disorder Society evidence-based medicine review concluded that there was insufficient data to recommend any specific drug for the long-term treatment of EDS in PD patients. Limited data exist for the use of wakefulness-promoting agents such as modafinil and armodafinil or stimulants such as methylphenidate or dextroamphetamines.

Modafinil

Methylphenidate

Caffeine

Sodium oxybate

Istradefylline

A single-center, open-label study reported that istradefylline, a selective adenosine A2A receptor antagonist, significantly improved EDS 2 and 3 months after PD patients received 2040 mg/d istradefylline once daily in the morning. The underlying mechanism may be that istradefylline enhances alertness while having no negative impact on sleep. Efficacy conclusion for istradefylline is under investigation. The use of istradefylline might be helpful in clinical practice, although further studies are warranted.

Atomoxetine

Insights Into Fatigue From Other Disorders

Although perceived fatigue is probably similar among different illnesses, there may be disease-specific differences. Both similarities and differences may provide insights into fatigue pathophysiology. Similarities in fatigue would be compatible with a hypothesis of shared mechanisms, and thus the possibility of similar interventions. The high prevalence of fatigue in medical and psychiatric disorders points either to some very generalized mechanisms or a limitation in the brains ability to distinguish perceptions. We limited our review of other disorders with prominent fatigue, but excluded chronic fatigue syndrome because of its frequent association with psychiatric disorders such as personality disorders and post-traumatic stress disorder that might confound physiological interpretations.

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Pathophysiology Of Fatigue In Pd

Most of the evidence suggests that fatigue is an intrinsic symptom to the pathobiological substrate of PD rather than a secondary or reactive phenomenon. For instance, it may precede motor symptoms in a substantial number of patients with PD. In most patients, fatigue did not correlate with PD duration or motor disability,, although some studies indicated that it worsened with underlying disease progression., , However, the interpretation of fatigue in PD is significantly confounded by its clustering with depression, anxiety, sleep disturbances, and apathy. Although it was present in over a onehalf of nondepressed patients with PD and in at least onethird of drugnaive patients in the initial motor stage of the disease, fatigue in PD was related to the severity of depressive symptoms., Fatigue was 1 of the diagnostic criteria for a Diagnostic and Statistical Manual of Mental Disorders, 4th editionbased diagnosis of both major depressive episode and generalized anxiety disorder. However, it is still not clear whether the observed overlaps of fatigue with affective disorders and apathy reflect a diagnostic bias or common pathophysiological mechanisms. A concept of primary fatigue and secondary fatigue has been proposed. In general, it is distinguishable from other related symptoms, such as depression, apathy, and sleepiness, suggesting that fatigue in patients with PD is largely a primary symptom and is not secondary to mood disorders, sleep alterations, or medications.