Why is it important to solve fatigue in PD? First, it is a debilitating symptom experienced by many people with PD; yet it is difficult to diagnose and treat. Perhaps more importantly, it is a symptom that people with PD and care partners told PDF was important when voting in the first Community Choice Research Awards survey.
This past October, I was pleased to lead a PDF Conference on Fatigue in PD in Chicago, IL. Because this meeting and subsequent research were inspired by the community, my colleagues and I feel it is important to let you know what happened and the progress we have made so far. At our meeting last year, along with the best minds in fatigue in PD and other diseases (see our full group listed at end), we had four goals before us: determine what we know, what we don’t know, what we can learn from other disciplines, and most importantly, where we should go next.
What Do We Know?
We know that fatigue is an underappreciated symptom of PD, which was only recognized in 1993. Since that time, studies have consistently demonstrated that fatigue is a significant problem for about half of people with PD.
We know that it is debilitating. In some studies, one third of people with PD rate fatigue as their single worst PD symptom, even more than tremor, rigidity or walking problems! About half rate fatigue as one of their three worst symptoms. We know that, although there is significant overlap with depression (many people with fatigue are depressed), many people with PD with fatigue are not depressed. We know that fatigue is not related to the severity of movement dysfunction and that it does not seem to be related to age, gender or duration of PD.
What Don’t We Know?
What Is It?
For most people, fatigue in general is a feeling of lack of energy, “total body give out,” or feeling “knackered,” which restricts activities. But people with PD report that their fatigue has a different quality than fatigue experienced prior to a PD diagnosis. So what is it? It is not sleepiness, as sleep and rest do not renew the energy. It is not weakness, as people with PD who experience fatigue are not weak.
Is it the same as fatigue in other diseases or is it unique? A recent study found that people with multiple sclerosis (MS) and PD filled out surveys about their fatigue pretty similarly. But is it really true? Does cancer fatigue feel the same as PD fatigue, as fatigue in MS or with depression? We don’t know and finding out may prove terrifically important.
Is it possible that ALL fatigue is caused by the same changes in the brain or might each one be distinct? If the same, then one treatment might help them all. If different, we may need a separate approach to each disorder.
How Can We Diagnose & Measure It?
It is difficult to study fatigue in large part because we do not have anything to measure other than the person’s report on how he or she feels.
While doctors can observe the severity of a person’s tremor, it is much harder to observe severity of fatigue. Some people with PD who have disabling fatigue may look so good that most non-experts would not notice anything wrong with them, whereas some people with PD, who are severely disabled by their inability to walk or even feed themselves, may not suffer from fatigue at all.
Lastly, many different medical problems cause fatigue, making it difficult to differentiate which one is the culprit. For example, depression and anxiety, both common in PD, both can cause fatigue. Apathy, a lack of interest or motivation, is frequently associated with fatigue. And these are just the problems that we often see in PD. Diabetes, congestive heart failure, cancer, anemia, lung disease, liver disease, arthritis and a plethora of other conditions also are associated with fatigue.
So, if a person with PD has fatigue and diabetes and breast cancer, how do we know which the culprit is, or if all three are involved?
How Can We Treat It?
There are many approaches to treating fatigue in PD, but none are proven to work. Our group identified better treatments as an area of need.
One option to consider is exercise. We know from one study, that some people with PD reported that exercise reduced their fatigue. Of course, some people might say, “If I could exercise I wouldn’t be complaining about fatigue!” Thus, it may not work for everyone. A second option to consider, if a person with PD is experiencing depression, is to treat that depression as soon as possible, with the hope that the fatigue is due to the depression. Additionally, any medications that might be contributing to fatigue should be stopped, if possible and, although sleepiness and fatigue are different, they do run together, so good sleep habits are encouraged.
Unfortunately, these are our only options at present.
What Can We Learn from Other Diseases?
The cancer field is way ahead of the PD field in understanding fatigue. They have been studying it for years. It turns out that fatigue is the single biggest problem in people who have survived cancer. In fact, it plagues over 30 percent of survivors even after they stop treatment. Some studies show that exercise may be helpful in these cases, but the most important factors that distinguish those with and those without fatigue are social. Marital status (being married), financial security, social-economic state, happiness, etc. are associated with less fatigue.
The cancer field has found that in fatigued survivors, it is common to see problems controlling blood pressure and heart rate. Should we look at this in PD? In PD, of course, blood pressure control is a problem for a large percentage of people but this has not yet been studied with relation to fatigue, nor has heart rate variability.
What about inflammation? In cancer, studies implicate an inflammatory response in the body as related to fatigue. Of course, therapies that regulate the immune system are a major part of cancer treatment, but why any inflammation continues to be present in those who are “cured” is unknown. Similarly, multiple sclerosis is an autoimmune disorder of the brain and spinal cord. Fatigue is more prominent and widespread in MS than in PD or cancer, and is often reported by individuals with MS when undergoing treatment with certain immune modulating drugs – strongly pointing to this immune factor as one contributor to fatigue.
Is the same true in PD?
Where To Next?
Like most scientific meetings we ended our discussion with the conclusion that more work needs to be done. However, unlike most meetings, we actually developed a path forward. This path forward is not a secret — we have submitted it for publication in a journal that everyone in the PD community will have access to: npj Parkinson’s Disease – PDF’s open access journal.[Update: since the date of publication of this blog post, this paper has now been published and can be accessed here.]
In addition to our assessment of the field, this meeting inspired my colleagues and I to form new collaborations and pursue interesting ideas to start moving forward in our understanding of fatigue. Together, we are looking at four research projects we’d like to pursue:
- The first (for which the initial work is being supported by PDF) will examine blood and spinal fluid samples from a large Scandinavian trial to determine if certain inflammatory markers may correlate with fatigue.
- A second study will try to obtain fMRI images from people with PD who have no other health issues causing fatigue. We want to compare brain images of the fatigued and non-fatigued. If we are lucky, we may identify a region in the brain that is implicated in causing fatigue. This might allow us to deduce possible brain circuits or neurotransmitters.
- A third avenue of research will mine existing data from the Michael J. Fox Foundation PPMI study to explore how many people with Parkinson’s disease report experiencing fatigue.
- Lastly, we are looking at a PET study already in progress, which is investigating inflammation in PD brains to see if fatigue in PD correlates with the inflammation. And we are going to look into funding from PCORI (Patient Centered Outcomes Research Initiative) to see if we can propose a large study of PD, MS, cancer and depression to find differences in the fatigue seen in these different disorders.
Through the Community Choice Research Awards, we have heard the community loud and clear – fatigue is debilitating and we need to do more to better understand and treat it. The good news is, we are making progress and will keep the community updated as we continue this research.
Joseph H. Friedman, M.D. is Chair of the PDF committee studying fatigue in PD, funded through a Community Choice Research Award. Dr. Friedman serves as Director, Movement Disorders Program, Butler Hospital and Professor and Chief, Division of Movement Disorders, Warren Alpert Medical School, Brown University.
Would you like to learn more about fatigue in PD? View Dr. Friedman’s webinar on the topic on the PDF website here. Browse the outcomes of this study in PDF’s scientific journal npj Parkinson’s Disease, here.
Fatigue in PD Committee:
Kelvin Chou, M.D. (Parkinson’s researcher and clinician, Ann Arbor, MI)
Gracia Clark, Ph.D. (person with PD, Bloomington, IN)
Diane Cook (person with PD, Denver, CO)
Chris Fagundes, Ph.D. (Cancer and fatigue expert, Houston, TX)
Karen Herlofson, M.D., Ph.D. (Parkinson’s researcher and clinician, Norway)
Lauren B. Krupp, M.D. (MS and fatigue expert, Stony Brook, NY)
Benzi Kluger, M.D., M.S. (Parkinson’s researcher and clinician, Aurora, CO)
Tony Lang, M.D. (Parkinson’s researcher and clinician, Toronto, Canada)
Jau-Shin Lou, M.D., Ph.D., M.B.A. (Parkinson’s researcher and clinician, Fargo, ND)
Laura Marsh, M.D. (Parkinson’s researcher and clinician, Houston, TX)
Anne Newbould (PD care partner, Cleveland, TN)
Daniel Weintraub, M.D., (Parkinson’s researcher and clinician, Philadelphia, PA)
PDF thanks its People with Parkinson’s Advisory Council and the ProjectSpark Foundation for their support and partnership on this initiative.