You Asked & We’re Answering: Fatigue in PD

friedman_joe_2015

Dr. Joseph F. Friedman

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.

Learn More

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.

13 thoughts on “You Asked & We’re Answering: Fatigue in PD

  1. Robin

    That was EXCELLENT for two reasons: 1) easy and succinctly written so it was easy to understand; 2) there were PATIENT on the team and not just research fellow and/or doctors working in COLLABORATION; 3) You had clear outcomes in which to define a way to move forward. Thank you for providing. Very much appreciated.

    Reply
  2. meredith adams, rn

    Thank you for earnestly looking at the problem of fatigue with PD. I am a 69 yo nurse, with many years experience with PD patients. I have enjoyed excellent health all of my life, but was diagnosed with PD 1 year ago. I am still actively working and thrive on exercise, including water aerobics several times each week. However, I am fatigued! Not always sleepy, but fatigued. Those around me, especially family, expect me to keep up the pace I have throughout my life.
    I also ache all over my body which makes me think there is an inflammatory component.

    I just wanted to cheer on the people who care and are researching this newly discovered symptom of the disease. Tell me how I may help! I will participate any way I am able. I live reasonably close to Sunnyvale, Stanford, and UCSF.

    Reply
    1. LISLE KOONE

      Meredith Adams,
      You have spoken well. My first diagnosis of PD was when I was 72 years old. I did not relate or connect my fatigue to the PD at that time but now it comes and goes to the point of disablement. My Pain now usually is accompanied by fatigue, Yet at church or other such social gatherings, when people ask how I am doing and I reply something like still hanging in there always say,”Well no matter how you feel you are looking great to me”
      BY THE WAY my first medical examination concerning fatigue was at the age of 16 years. The Family doctor who examined me gave the diagnosis of, “GROWING PAINS.” TREATMENT “YOU WILL GROW OUT OF IT”.
      My mother understood my problem and worked with me but my siblings and class mates heckled me and made fun of me. Yes be prepared for people to not understand and sometimes be less than kind.
      I have three other on going medical conditions but that does not stop me from being involved i a study at UTSW Dallas,Texas.

      Reply
  3. Vincent Joy

    Excellent Review of Fatigue in PD.
    As a PDer frequently plagued by fatigue & depression (always for me) in the late afternoons, I found that I am able to eliminate it by maintaining adequate hydration, and taking my Sinemet tabs an hour earlier (at 5 PM instead of my usual 6 PM). As long as I avoid dehydration & prevent the “wearing off” effect of my last dose of Sinemet by taking it an hour early, both fatigue and depression seem to disappear for me. This may not work for all.

    Reply
  4. Bill Crawford

    You identified the situation with fatigue very well but there was not a single recommendation on how to deal with it. Surely there are some things you can suggest.

    Reply
    1. Karen Hedrick

      Bill,
      I thought exactly the same thing. Basically it was an article saying we don’t know anything new. Sorry to be so critical but I have read so many of these. I want to read something with some helpful information.

      Reply
  5. Linda Jamme

    My husband has PD and severe fatigue. He was diagnosed about 8 years ago and now sleeps off and on all day. He is in bed most of the day and only sits up in a chair for the two meals he eats. When he was first diagnosed with PD he complained a lot about pain in his feet but since he is in bed nearly 90% of the day he no longer has this pain.
    Before he started to have any PD symptoms he was very self motivated and exercised all the time and now it is hard to get him to do anything. He could shave but chooses to have me do it. He just will not do anything for himself.
    It would be great to see any kind of progress made in this part of the disease. I realize some of the symptoms can be related to age but certainly not to the extreme that he has. Keep up the good work and study on this disease.

    Reply
  6. Christine

    What about patients who have paradoxical responses to exercise? The studies may say that most people with PD benefit from exercise, but some patients exert themselves and their medicine stops working. Seems like there might be a study there….

    Reply
  7. Marilyn

    Is anyone looking at mitochondrial dysfunction in relation to fatigue with PD. My fatigue, which is most pronounced at end of a med cycle or late in the day (coinciding with “off” time) is like the “burn” one experiences during intense physical activity.

    Reply
  8. PM Parkhill

    It would change our lives!!! having parkinson for 14 years on a average day I need close to 19 hrs to rest my body to embrace 3-5 hrs of joy. I meditate, read and prayer to occupy my mind while my body rest. I take a combination of vitamins and nootropics. It helps with clarity but not my physical fatigue. Herbal supplements haven’t given any success for the fatigue but remain open minded if one is found to work. I also live with Parkinson’s pain ( another symptom not properly addressed)

    Reply
  9. PB

    As a PD patient for 16 years now (age now 65) I am grateful to you for noticing the fatigue / PD association. About a year ago I began to have the “wearing off”‘ issues, primarily fatigue. The fatigue was more than sudden exhaustion…more like a heaviness feeling in my arms and legs that kept them from moving. Myasthenia Gravis came to mind – when I took my Stalevo the feeling lifted within 15-30 mins.. I began to wonder if there were connections between the 2 neurological disorders? I know I have severe arthritis (inflammation ) since well before diagnosis with PD . I am having m y 2nd knee replaced in 2 weeks….8 weeks after the first one. Severe bunions developed in my 30’s ….perhaps a genetic link or precursor to PD as well?
    Thank you for thinking outside the box and keeping hope for a cause or cure alive. PB

    Reply
  10. Jan Syers

    Thank you, thank you, thank you! Fatigue has been my constant companion since this started but no one has actually acknowledge as part of the disease. I thank you so much for your research and possible treatment.
    Sincerely,
    Jan Syers

    Reply
  11. Judith Brown

    This was somewhat of an interesting article, sadly there is still no clear reason for fatigue or other symptoms.

    My mother was diagnosed with PD at the early age of 35. She went through many test and procedures, including a Palidottomy .

    She survived to be 80 years old. She had many symptoms that are common with this disease. However, regarding her fatigue, it seemed to be linked with when she would take her medication ( was she over medicated?) it also made a difference after meals.

    I’m not specialist ( although I feel like I could be one after watching how Parkinson’s disease effected my mother over 45 years) .

    I don’t know if my opinion has any proof, but I wanted to put it out there.

    Thank you to all of the specialist who are trying to find answers and cures to these awful diseases that take over one’s body.

    Lavera’s Daughter

    Reply

Leave a Reply

Your email address will not be published. Required fields are marked *