Protein May Hold Clues to Development of Parkinson’s
Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.
Alpha-synuclein (αSyn)is a protein central to Parkinson’s. In Parkinson’s, this protein misfolds, forming a clump in the brain. Large clumps are known as “Lewy bodies” and disrupt the brain’s normal functioning in people with PD.
Alpha-synuclein is also involved in the regulation of lipids and fatty acids, which help to prevent disease-associated changes in the brain. In Parkinson’s, alpha-synuclein is destabilized. This makes the protein more likely to break down and clump together. What triggers the destabilization of alpha-synuclein in the human brain remains one of the most critical questions in the study of Parkinson’s.
Tim Bartels, MSc, PhD, from Brigham and Women's Hospital Inc., received a Parkinson’s Foundation research grant to gain a better understating of alpha-synuclein in Parkinson’s. He and his research team will analyze the interactions of lipids with different forms of alpha-synuclein in human brain samples. Dr. Bartels hopes to discover which lipids and fatty acids prevent alpha-synuclein aggregation and which ones promote aggregation.
He will also investigate the normal interaction of alpha-synuclein with fatty acids and lipids. Together, these approaches should suggest how to develop drugs that stabilize alpha-synuclein by mimicking the beneficial lipids and fatty acids.
Dr. Bartels team may also find a signature of specific lipids and fatty acids that are associated with PD. This could be an easily accessible biomarker — a biological molecule that is a sign of disease — for Parkinson’s. Having a biomarker for Parkinson’s could lead to earlier diagnosis of the disease. This can improve outcomes for people living with PD.
The Parkinson’s Foundation Stanley Fahn Junior Faculty Awardhelps ensure promising early career scientists stay in the PD research field. This award provides junior investigators the support they need to develop their own independent funding source.
What’s Next: Reporting Our Findings
Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.
Breaking News: Economic Burden of Parkinson’s Disease is $52 Billion
A new study resulting from a partnership of Parkinson’s organizations and industry partners reveals that the economic burden of Parkinson’s disease (PD) in the U.S. is $51.9 billion – nearly double previous estimates.
Study Highlights
$25.4 billion is attributable to direct medical costs, such as hospitalizations and medication.
$26.5 billion is attributable to non-medical costs, such as missed work, lost wages, early forced retirement and family caregiver time.
The U.S. government accounts for nearly $25 billion in spending related to PD, with $2 billion through Social Security and the remaining $23 billion through Medicare.
Why is this study important?
Understanding the annual economic toll on people with PD, their families and the government helps when advocating for more federal funding for Parkinson’s research. It also allows us to better serve people with PD and their families with programs to help them live better with the disease, touching on areas they are most concerned about and where we can have the most impact.
How was the study performed?
The study, The Economic Burden of Parkinson’s Disease, was sponsored by The Michael J. Fox Foundation, with support from the Parkinson’s Foundation, several industry groups (ACADIA, Adamas, AbbVie, Acorda and Biogen), the American Parkinson Disease Association and The Parkinson Alliance.
The Michael J. Fox Foundation, with support from the Parkinson’s Foundation and other community organizations and industry partners, used data from public databases including Medicare, the Centers for Disease Control and Prevention and the Census Bureau. Several Parkinson’s organizations, including the Parkinson’s Foundation, assisted with data collection through sharing a survey across websites, social media networks and email communications. This joint effort resulted in the most comprehensive assessment illustrating the annual economic toll on the Parkinson’s community and the U.S. government in history.
How can I get involved in Parkinson’s research?
People with PD and their loved ones can help speed the cure and find medications to reverse its course. The Parkinson’s Foundation pairs people in the PD community as primary research partners with scientists, industry and government to prioritize research areas, improve studies and influence stakeholders. Learn more about our Research Advocates program.
Learn More
Another recent large-scale study about Parkinson’s disease is the Parkinson’s Foundation Parkinson’s Prevalence Project. This study established accurate estimates of the prevalence of Parkinson’s throughout North America, which will help the Parkinson’s Foundation attract the attention of federal and state government as well as the pharmaceutical industry to the growing need and urgency in addressing PD. Read more about the prevalence of Parkinson’s.
What’s Hot: What should I do if there is a Sinemet (Carbidopa/Levodopa) shortage?
In this month’s What’s Hot in Parkinson’s disease? column, I review what is becoming a hot topic: a Sinemet shortage. Recently, many people with Parkinson’s disease (PD) have been informed by their pharmacy that there is a shortage of Sinemet or that their brand of Sinemet has been “discontinued.” What should you do?
In 2010-2011 there was a national shortage of Sinemet. This occurred as the brand was transitioned from Merck and Company, Inc. to Mylan Pharmaceuticals, Inc. In 2019 Merck announced that it would no longer be manufacturing Sinemet CR (extended release). These national news stories led to panic.
Generic formulations cause worry. We field many calls to the Parkinson's Foundation Helpline about this topic. Callers are concerned about a wide range of topics from weaker efficacy of the generic, worsening of Motor fluctuations, dyskinesia, allergy and skin rash. When switching to a generic form, people with PD should keep in mind that there may be as much as a 20% difference in treatment effect. However, a generic may sometimes be desired, especially in people with Parkinson’s who experience dyskinesia from tiny medication dosages (some people have referred to these cases as “brittle” PD).
Keep in mind that the U.S. Food and Drug Administration (FDA) approval of a brand name drug requires demonstration of its pharmacokinetics, efficacy, safety and tolerability in both a healthy population and in the Parkinson’s population. In contrast, approval of a generic drug only requires demonstrating its bioequivalence in the blood, but not its clinical treatment effect in Parkinson’s disease.
It is important not to panic when your “brand” or “generic” Sinemet become unavailable. There are many alternatives. Here are a few tips:
If you have had Parkinson’s more than five years, in many cases the CR (extended release) tablets offer little to no advantage over standard regular release for many people.
Sometimes a CR tablet can be useful for “peak dose” dyskinesia, but it rarely helps extend the life of Sinemet after the first few years following a PD diagnosis.
While individuals cannot control the manufacturer that their pharmacist chooses for their medications, talk to your pharmacist and let him/her know how helpful it is for you to have a consistent version of carbidopa/levodopa.
If you are able to maintain a pill made by the same manufacturer; then you can adjust the timing and the dose (by as little as ½ or ¼ tablets) to achieve an optimal strategy.
The Eight Sinemet Limit
Another important issue has been the “eight Sinemet limit.” Pharmacies and insurance companies have been citing the language in the original FDA approval of Sinemet and denying prescription requests for people with PD who request more than eight tablets a day. The advent of electronic medical records has worsened this difficult issue for people with PD, as automatic limits are now being set by nationalized computer systems. Once limits are in computer systems, they can be challenging for patients to change. If your insurance carrier or pharmacy blocks filling of your Sinemet prescription purely based on the number of daily pills, we suggest you contact your doctor, send an appeal letter and also contact the Parkinson's Foundation Helpline at 1-800-4PD-INFO (473-4636), as we are here to assist you.
Reasons to try Sinemet CR (ER) or Rytary
Medication dosages taking too long to “kick in” and start working
Medication wearing off before the next scheduled medication dose
Severe on-off medication fluctuation periods (e.g. rapid cycling during the day ranging from feeling completely on medication to completely off medication)
Dyskinesia (too much movement, usually resulting from too high of a blood level of dopamine)
Too many pills
Too many medication dosage intervals (e.g. taking medications every 1-2 hours throughout the waking day)
The below conversion may be useful if trying the extended release Rytary (Hauser et. al.):
Finally, doctors are here to optimize the timing and medication combinations that work best for each patient ― a critical part of that is finding the best dopamine replacement therapy. The “timing is critical principle” from Parkinson’s Treatment: 10 Secrets to a Happier Life should be considered during dose adjustments for any person living with Parkinson’s. Timing is an important element to the success of any Parkinson's treatment. If your formulation changes or a manufacturer discontinues your medication, your care team is here to help you find the best and most positive path forward.
Selected References
Go CL, Rosales RL, Schmidt P, Lyons KE, Pahwa R, Okun MS. Generic versus branded pharmacotherapy in Parkinson's disease: does it matter? A review. Parkinsonism Relat Disord. 2011 Jun;17(5):308-12. Epub 2011 Mar 1. Review.
Okun MS. Parkinson's disease patients cannot get their dopamine replacement: The 8-sinemet limit. Mov Disord. 2011 Dec 9. doi: 10.1002/mds.24038. [Epub ahead
of print].
Pahwa R, Lyons KE, Hauser RA, Fahn S, Jankovic J, Pourcher E, Hsu A, O'Connell M, Kell S, Gupta S; APEX-PD Investigators. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord. 2014 Feb;20(2):142-8. doi: 10.1016/j.parkreldis.2013.08.017. Epub 2013 Sep 5. PubMed PMID: 24055014.
Hauser RA, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M, Ondo W, O'Connell M, Gupta S; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomized, double-blind trial. Lancet Neurol. 2013 Apr;12(4):346-56. doi: 10.1016/S1474-4422(13)70025-5. Epub 2013 Feb 26. PubMed PMID: 23485610.
Parkinson’s disease (PD) results in the loss of dopamine-producing cells in the brain. Because dopamine cannot cross the blood-brain barrier (a safety feature of the brain), people cannot simply take dopamine pills. The drug levodopa (L-dopa) — a precursor to dopamine and the gold standard for treating PD — does have the ability to cross the blood-brain barrier, where it successfully converts into the much-needed dopamine.
Since 1971, scientists were aware that one or more of the many microorganisms living in the human gastrointestinal tract prematurely convert the L-dopa into dopamine before it gets into the brain― but they didn’t know which ones. To combat some of this loss, L-dopa is usually combined with carbidopa to help block the premature metabolism, as well as help with the common side effects of nausea and vomiting.
Only about 44% of the L-dopa makes it to the brain. There are many different types of microorganisms, such as bacteria, viruses and fungi. Understanding which ones may affect this process could help improve the efficiency of levodopa as a treatment for PD.
A study titled, “Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism” (Maini Rekdal, Bess, Bisanz, Turnbaugh, & Balskus, 2019), sought to decipher the molecular mechanisms by which gut bacteria might be responsible for this degradation of L-dopa en route to the brain. A complex undertaking, researchers used several, highly sophisticated methods, from running tests on the microbiome (trillions of microorganisms that help keep the body running smoothly) to evaluating inhibitors and testing the gut microbiota of people with and without PD.
Results
In the gut, some of the L-dopa was converted into dopamine by an enzyme from the common gut bacteria (Enterococcus faecalis).
Then, the dopamine (still in the gut) was further metabolized into a compound called m-tyramine, by an enzyme from a second bacterium (called Eggerthella lenta).
The enzymes from these two bacteria (Enterococcus faecalis and Eggerthella lenta) appear to be responsible for L-dopa metabolizing first into dopamine and then into m- tyramine, prior to reaching to blood-brain barrier, thereby diminishing how much L-dopa and the dopamine treatment successfully makes it to the brain.
Carbidopa is successful in inhibiting the metabolism of L-dopa by human enzymes, but not by the bacterial enzymes in the human gut.
When L-dopa was given to lab rodents orally along with a bacterial enzyme inhibitor called AFMT, this prevented metabolism of L-dopa and resulted in improved bioavailability of the drug in the animals’ blood stream.
What Does This Mean?
Using a complex set of steps, this study identified two enzymes in human gut microbiota (called Enterococcus faecalis and Eggerthella lenta) that are key to impeding a significant portion of the L-dopa from reaching the brain.
Further, in lab rodents, researchers increased the amount of L-dopa reaching the brain, by manipulating the activity of these enzymes in the gut with a drug, AFMT. This suggests that this approach (inhibiting bacterial enzymes) could possibly be developed for human use. In short, they may have found a drug that can reduce the premature metabolism of L-dopa into dopamine in the human gut, ultimately improving the efficiency of L-dopa treatment.
Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J., & Balskus, E. P. (2019). Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science, 364(6445). doi:10.1126/science.aau6323
Ask the Experts: The Challenges of Using Marijuana as a Parkinson's Treatment, Part 2
Medical marijuana, or cannabis, is one of the most popular topics among the Parkinson’s disease (PD) community ― for people with PD, health professionals and researchers, alike. Earlier this year, the Parkinson’s Foundation hosted its first-ever convening on marijuana and Parkinson’s. Among the 46 attendees, of which 17 gave presentations, there was a reoccurring theme: what are the biggest hurdles the PD community faces when it comes to medical marijuana?
This is the second article in a two-part series. Read part one here.
Adverse Effects
Some of the most common side effects of cannabis-based products include:
drowsiness and fatigue
dizziness
dry mouth
anxiety
nausea
cognitive effects
Specifically, for smoked forms, side effects include cough, increased phlegm and bronchitis. Some rare but important side effects to note include: orthostatic hypotension, paranoia, depression, worsening of coordination of movement and rapid beating of the heart.
Specifically, regarding cognitive function, one review article of several studies found that attention and concentration were impaired in the short term (0-6 hours after use) but largely returned to normal in the longer term (three weeks or longer after use). However, decision making and risk taking were impaired three weeks or more after last cannabis use. Working memory was impaired shortly after use, but did not see any residual or long-term effects. Mixed results were seen as to whether there are long-term effects on impulsivity and verbal fluency after cannabis use.
→ Danny Bega, MD, MSCI, from Northwestern University Feinberg School of Medicine, spoke about this topic at the marijuana convening.
Finding the Right Formula
Physicians and pharmacologists are constantly trying to define the limits of their practice when it comes to cannabis. Not only must researchers find the right formula, they must also find the right delivery method. Cannabis can be delivered in various forms, from liquids to e-liquid (vapor) and inhalers to patches.
One additional challenge is that cannabis products are not highly regulated, so there can be a lot of variation from product to product and even from batch to batch within a single product. This needs to be regulated more so that people can know what is in the product they are purchasing and trust that it is safe.
→ Bill Arnold, CEO of Cannoid, LLC, spoke about this topic at the marijuana convening.
The Effects of Cannabis and Pain on Men VS Women
Of the 20 common conditions that qualify for medical marijuana, chronic pain has substantial evidence supporting the use of cannabis. People with PD report pain as one of the most common non-motor symptoms, which is not always responsive to pain medications.
PD-related pain is most common among women. Differences between men and women specifically in their susceptibility to intoxication and abuse liability have not been studied. Preclinical evidence suggests that female laboratory animals are more sensitive to cannabinoid (THC) relative to males in terms of treating pain, but they are also more sensitive to the abuse-related effects of these drugs. However, female animals develop tolerance to the pain-relieving effects of THC at a faster rate than males, rendering THC close to ineffective in females.
Ziva D. Cooper, PhD, and her colleagues tested cannabis to see if these findings in animals would translate to humans. Her study found that women who heavily smoke cannabis did not show a pain-relieving response, whereas men did. Regardless of pain response, women reported feeling as intoxicated as men and reported liking the cannabis as much as men.
Future studies investigating the use of cannabis and cannabinoids for PD-related pain are warranted. These studies should consider differences between men and women, cannabis experience and adverse effects.
→ Ziva D. Cooper, PhD, from the UCLA Cannabis Research Initiative, spoke about this topic at the marijuana convening.
The medical marijuana convening brought together a diverse group of experts from academia, clinics, industry, government and the Parkinson's community to establish a consensus on medical marijuana use in PD. The Parkinson’s Foundation will publish its findings on the convening in summer 2020.
Ask the Experts: The Challenges of Using Marijuana as a Parkinson’s Treatment, Part 1
Medical marijuana, or cannabis, is one of the most popular topics among the Parkinson’s disease (PD) community ― for people with PD, health professionals and researchers, alike. Earlier this year, the Parkinson’s Foundation hosted its first-ever convening on marijuana and Parkinson’s. Among the 46 attendees, of which 17 gave presentations, there was a reoccurring theme: what are the biggest hurdles the PD community faces when it comes to medical marijuana?
This is the first article in a two-part series. Read part two here.
Treating Parkinson’s Symptoms with Cannabis
There is not enough evidence yet to support that medical marijuana can help manage Parkinson’s symptoms, however there are studies on the topic. Unfortunately, they have mixed results. Generally, the studies have been small and some with no control groups. The effects of medical marijuana are not completely understood, especially in the PD population. The bottom line is that more studies are needed, specifically larger and more rigorously conducted studies.
Based on some observational studies, cannabinoids (the active molecules in marijuana) may potentially benefit some non-motor symptoms of PD including pain, anxiety, sleep problems (insomnia, RBD, RLS), weight loss and nausea. Potential adverse effects include dizziness, blurring of vision, loss of balance, mood and behavioral changes, hallucinations, and impaired cognition and motivation. Better studies are necessary to confirm these benefit and adverse effects for people with PD.
Controlled clinical trials of cannabinoids (where some people receive the drug and some do not) have reported mixed results for treating motor symptoms and levodopa-induced dyskinesia as well as improving quality of life.
While stories and videos exist showing that marijuana can treat PD symptoms, the challenge is showing that cannabis is better and safer than treatments that are currently available. A recent survey shows that the health community does not have a consensus on using cannabis as a treatment. This reflects lack of data, knowledge and training on the subject.
Future studies about medical marijuana and Parkinson’s should follow the highest standards of clinical trials to focus on:
Delivery type: do specific strains, soft gels, tinctures (alcohol-based cannabis extract), e-liquid (vapor), topicals, infused food, flower products, inhalers and patches treat symptoms differently and have different side effect profiles?
Dosage: what is the minimum dosage to guarantee effectiveness, what is the maximum dose tolerated and what dose will have a sustained benefit? Furthermore, how does this differ by strain and formulation?
Effect on motor vs non-motor symptoms: which symptoms can improve, worsen or stay the same with cannabis use?
Interaction with PD medications: how does cannabis interact with medications taken for PD symptoms?
Key component: What components of cannabis/marijuana provide the best response in PD with the least risk of side effects? What is the optimal CBD (Cannabidiol) to THC ratio?
PD-specific side effects: are people with PD uniquely susceptible to certain side effects that are not seen in the general population?
Lastly, there needs to be a widespread physician education on using cannabis as a treatment ― almost all physicians surveyed agreed that medical school curriculums should include education on cannabis.
→ Danny Bega, MD, MSCI, from Northwestern University Feinberg School of Medicine; Joseph Jankovic, MD, from Baylor College of Medicine; and Karl Kieburtz, MD, MPH, from the University of Rochester, spoke about this topic at the marijuana convening.
Potential Drug Interactions
One surprising fact shared at the meeting is that cannabis-based products have the potential to interact with other medications. Given that people with Parkinson’s may be on multiple medications for other conditions, it is important to be aware of these interactions to avoid complications.
Epidiolex® is the first FDA-approved cannabinoid prescription drug. It is an oral solution of cannabidiol most commonly used to treat rare forms of epilepsy. It has been shown to have interactions with many anti-seizure medications, some antibiotics and medications for lowering cholesterol, pain, anxiety, depression and blood pressure. In some cases, Epidiolex can make these medications more or less potent. In other cases, these medications can make Epidiolex more or less potent. Because Epidiolex largely contains cannabidiol, there is the possibility that other cannabis-based products may also interact with medications in a similar way.
Delta-9-tetrahydrocannibinol (THC) is the primary psychoactive component of marijuana (the part that gives a “high”). It can take a long time to take effect and cannot be easily measured for a therapeutic or medicinal dose. THC can also interact with certain medications such as valproic acid (for bipolar disorder, seizures, and migraines) and can result in increased psychoactive effects of marijuana.
Medical marijuana can be taken in an edible form. Care should be taken with this form, as it takes longer to feel an effect and lasts longer (4-8 hours as opposed to 2-3 hours for smoking or vaporizing). Often, because the effects are slow, people increase their dose, eating more, which can be dangerous. Edibles may also have more toxicity than smoked marijuana, because they are broken down by the liver into more toxic chemicals.
→ Jacqueline Bainbridge, PharmD, FCCP, MSCS, from the University of Colorado, spoke about this topic at the marijuana convening.
The medical marijuana convening brought together a diverse group of experts from academia, clinics, industry, government and the Parkinson's community to establish a consensus on medical marijuana use in PD. The Parkinson’s Foundation will publish its findings on the convening in summer 2020.
Parkinson’s disease (PD) is largely known for its motor symptoms, slow movement, tremor and stiffness, but other wide-ranging challenges, known as non-motor or non-movement symptoms — can often be most problematic. Treating these non-motor symptoms promotes optimal living.
The following article is part two of a series based on a Parkinson’s Foundation Expert Briefings webinar exploring the latest research and treatments in PD-related non-motor symptoms, by Ronald Pfeiffer, MD, Oregon Health and Sciences University, a Parkinson’s Foundation Center of Excellence. Read part one next.
Gastrointestinal Functions
Gastroparesis is a condition that prevents the stomach from emptying properly. For many with PD, spontaneous stomach muscle movement is impaired, preventing food from easily emptying. This creates a feeling of fullness after a few bites of food, causing reduced appetite. Symptoms include nausea, vomiting, heartburn, bloating and weight loss. Diet and medications, including BOTOX® injections to the pyloric sphincter (a muscle that helps the movement of partially digested food and liquids) are among treatment options. Dopaminergic medication delivery systems may also avoid gastroparesis.
Small Intestinal Bacterial Overgrowth (SIBO): While this recurrent non-motor gastrointestinal issue has not been well-researched in Parkinson’s, one study showed that up to 54 percent of people with PD experience it. Decreased gut motility, which is common with PD, can lead to SIBO, characterized by:
Increased bacterial density in the small intestine
Presence of colonic-type bacterial species in the small intestine
SIBO can result in malabsorption (condition that makes it difficult to digest and absorb nutrients from food) and might explain weight loss in PD. When experiencing SIBO, levodopa and medications may take longer to work, wear off more quickly or not work at all, because they must travel to, and through, the stomach to be effective. Antibiotics may help.
Constipation: This can be chronic in PD. It can be caused by physical changes due to the disease and/or PD medications. Increasing dietary fiber, through food and supplements, increasing fluids and exercise, and minimizing starchy foods can all be beneficial. More than 60 percent of people with PD experience increased straining, pain and incomplete evacuation of their bowels. Dopaminergic medications, including apomorphine injects, BOTOX® injections or biofeedback techniques may offer relief.
Cardiovascular Functions
Orthostatic hypotension: More than half of people living with PD experience a significant blood pressure drop upon standing; certain medications can worsen this. This drop can cause lightheadedness or fainting, fuzzy vision, foggy thinking, headache, lower back ache, lethargy or fatigue. Increase blood pressure or reduce lightheadedness by:
Drinking 12-16 ounces of cold water before standing
Crossing legs or flexing calf muscles can
Eating small, frequent meals and increasing fluids and salt
Making slow position changes
Wearing abdominal binders or pressure stockings that reach the waist, like pantyhose
Talking to your doctor about blood pressure medications
Postprandial hypotension: Occurs when a person’s blood pressure drops after eating. Meals heavy in carbohydrates can worsen the condition, which develops within 15 minutes of eating and may persist up to three hours after. Ease symptoms by consuming less carbohydrates at meals or napping after eating.
For others with PD, blood pressure can rise too high when lying down; blood pressure can also rise drastically at night. Discuss prescription treatments with your doctor.
Bladder Functions
Overactive bladder can occur in more than 80 percent of people with PD, causing frequent or nighttime urination, urination in small amounts, the sudden need to urinate and involuntary leakage. Newer anticholinergic (treat multiple urinary conditions, including incontinence and overactive bladder) drugs (including trospium (Sanctura®), darifenacin (Enables®) and solifenacin (VESIcare®), can treat incontinence and overactive bladder, as can mirabegron (Moretti®), which fosters bladder relaxation and increases bladder capacity. Detrusor muscle BOTOX ® injections can also improve urinary dysfunction.
Obstructive urinary symptoms: These issues account for less than 40 percent of PD-related urinary problems and are often characterized by urinary hesitancy or a weak stream. These features may lead to overflow incontinence, which can cause unexpected urine leakage due to an overfull bladder. Medications, including alpha blockers (terazosin, doxazosin, or tamsulosin), 5-alpha-reductase inhibitors (dutasteride or finasteride) or a parasympathomimetic agent, such as bethanecol, as well as intermittent catheterization, may improve obstructive urinary symptoms. Talk to your doctor about symptoms and treatment.
Sexual Functions
Sexual dysfunction in PD affects women and men. Women may undergo reduced vaginal sensitivity or reduced desire. Men may experience erectile dysfunction or decreased desire or orgasm. Testosterone therapy can improve decreased libido in men, while water-soluble lubricants can improve lubrication. Discuss treatment options with your doctor.
Prescription treatment of erectile dysfunction may include PDE5-inhibitors, including sildenafil (Viagra®), tadalafil (Cialis®) and vardenafil (Levitra®); sublingual apomorphine; or intrapenile injections of a vasoactive drug, such as alprostadil (Caverject®) or papaverine.
Thermoregulatory Functions
This inability to regulate body temperature can manifest as excessive sweating, or a drastic rise or drop in body temperature. Excessive sweating (hyperhidrosis), experienced by more than 50 percent of people with PD, consists of sudden, drenching sweats of the head and neck. Though it may occur in people taking no PD medications, it often occurs as prescriptions wear off or during episodes of dyskinesia. Adjusting dopaminergic therapy can help. One study suggests subthalamic deep brain stimulation (DBS) may also help. BOTOX ® injections can be used if sweating is localized to armpits.
Fatigue
Present in almost 60 percent of people with PD, fatigue is an understudied non-motor symptom. It is often ranked by people with PD as one of their most disabling symptoms. It’s still unclear whether fatigue in PD is a brain or muscular problem; currently there are no well-formulated treatments. While medications have been tried with inconsistent results, some studies suggest exercise helps.
Breathing Difficulties
Some people with Parkinson’s experience shortness of breath; this is due to chest wall muscle rigidity preventing full chest expansion. Adjusting medications to reduce “off” times and dyskinesia can help. Treating anxiety or obstructive sleep apnea, if present, can also help, as can inspiratory and expiratory muscle strength training.
Contact our Helpline at 1-800-4PD-INFO (1-800-473-4636) or Helpline@Parkinson.org for answers to your Parkinson’s questions. Helpline specialists can assist you in English or Spanish, Monday through Friday, 9 a.m. to 7 p.m. ET.
Meet the Researcher: Gene Mutation That Promotes Protein Aggregation Could Spur Parkinson's
Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.
A key feature of Parkinson’s disease is abnormal protein clumping within nerve cells or neurons. These protein clumps, called aggregates, spread throughout the nervous system as Parkinson’s progresses. How this occurs remains unclear.
Mutations in the GBA1 gene are a strong genetic risk factor for developing Parkinson’s. They are also linked with faster progression of motor and cognitive symptoms.
Marie Ynez Davis, MD, PhD, of VA Puget Sound, received a Clinical Research Award from the Parkinson’s Foundation to investigate a potential new role for the gene GBA1 in speeding the spread of protein aggregates through exosomes. These are small bubble-like structures released by neurons and other cells. They contain proteins and other material that can travel and be received by other neurons and cells.
Dr. Davis’ goal is to find out whether a lack of GBA1 influences the development of Parkinson’s by increasing the number of exosomes and the proteins inside them that can be delivered to other neurons. This could promote clumping in the receiving neurons throughout the nervous system.
To achieve this goal, she will study human neurons from people with GBA1 mutations and Parkinson’s. She will examine the development and structure of exosomes. She will also look at their ability to promote protein aggregation.
Our hope is that results from this work will improve our understanding of how Parkinson’s occurs. It may also reveal new targets for therapies that could halt or slow progression of the disease.
Parkinson's Foundation Clinical Research Awards help facilitate the development of clinician scientists, ensuring that promising early career scientists stay in the PD field to help us solve, treat and end this disease.
What's Next: Reporting Our Findings
Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.
Podcast Playlist: Our Top Podcast Episodes to Get you Through Fall
While the leaves may be changing, your favorite podcast isn’t going anywhere! Cozy up, sit back and get ready to learn from our Parkinson’s disease (PD) experts with our top Substantial Matters: Life and Science of Parkinson’spodcast episodes:
Stall the Fall
People with Parkinson’s are two times as likely to fall as other people their age. While healthcare professionals recognize the extent of the problem, there is still a lot to learn about why they happen and what can be done to prevent them.
Depression in Parkinson’s
With depression as a common PD symptom, people with Parkinson’s should be conscious of their increased susceptibility to seasonal depression. Learn about the symptoms that accompany depression and how they may overlap with PD itself.
Seeking a Second Opinion After a Parkinson’s Diagnosis
People are being newly diagnosed with Parkinson’s year-round. Learn more about seeking a second opinion from a movement disorders specialist. It may help to confirm the diagnosis and address any lingering unanswered questions.
Addressing Sleep Discomfort with Parkinson’s
The seasonal time change can lead to trouble sleeping for everyone, but people with PD experience sleep problems as a symptom. Changes in the brain can affect mood, thinking and the sleep-wake cycle. Find out how to address sleep discomfort.
Palliative Care as Supportive Care in PD
A change in temperature can bring muscle stiffness. As people with PD understand the benefits of palliative care, they are adding it to their regimen. Palliation means to ease the burden of the symptoms of a disease.
Dance Therapy for PD
A change of season can be the perfect time to try something new. Besides medication, people with Parkinson’s can benefit from many other forms of therapy, including physical, occupational, speech, music, art therapies, along with dance/movement therapy (DMT).
Q&A with Diane M. Ellis, Parkinson's Expert and Nurse
Diane M. Ellis, MSN, RN, CCRN is a clinical assistant professor at Villanova University M. Louise Fitzpatrick College of Nursing and Edmond J. Safra Nurse Faculty Scholar. As a recipient of the first Parkinson’s Foundation Nurse Faculty Award, she received grant funding to launch a project to help make life better for people with Parkinson’s disease (PD).
What are the highlights of your Parkinson’s Foundation Nurse Faculty Award project?
Diane: The purpose of this study: An Intraprofessional Mock Code: Nurse Anesthesia and Baccalaureate Nursing Students – Parkinson’s Disease Patient Missed/Omitted/Delayed (MOD) Medication Simulation Case Study was to increase awareness and educate undergraduate nursing and graduate nurse anesthesia students about the importance of timely administration of Parkinson’s medication. missed/omitted/delayed PD medications during care transitions. We studied the intraprofessional collaboration between the students , communication and comfortability between the students during a simulated emergency code situation of a an unfolding mock code simulated hospitalized patient with PD.
Because omitted medications compromise patient safety, quality improvement strategies that focused on safe and timely medication administration and medication reconciliation during care transitions were undertaken. Pre-test/Post-test results were compared post mock code simulation and debriefing from the participating students .
What were the study findings?
Diane: Overall, more than half of the undergraduate senior nursing students who participated in the study were unable to correlate a patient’s declining health as missed doses of PD medication until the second half of the case, when the connection became apparent. By the end of the study, students showed a:
53.6% increase in knowledge regarding the importance of PD medication timing.
54.3 % increase in knowledge regarding best practices to prevent missed or omitted PD medications.
71.3 % increase in knowledge regarding side effects and complications of missed or omitted PD medications.
46.8% increase in knowledge regarding priority nursing care practices for patients with PD.
Among faculty who participated, study results also showed a:
71.4% increase in faculty knowledge regarding the importance of PD medication timing
57.1% increase in faculty knowledge regarding best practices to prevent missed or omitted PD medications
85.7% increase in faculty knowledge regarding side effects and complications of missed or omitted PD medications
57% increase in faculty knowledge regarding priority nursing care practices for patients with PD.
What did it mean to you to receive the Parkinson’s Foundation Nurse Faculty Award?
Diane: My team and I were very happy to receive funding to conduct this study as it gave us the ability to pay for essential personnel to assist in this study and to support students and faculty in the dissemination of the results of this study.
How did the study simulation help educate the nursing students involved?
Diane: I believe study results speak for themselves regarding how the students gained pertinent and lifelong knowledge in PD care. This simulation was the perfect environment for high risk low volume patients. These students previously received a two-hour PD lecture, but still were unable to answer the most basic PD questions related to the care of patients with PD and their medication administration.
Due to the nature of the simulation, the students reacted and participated as if this were a hospital setting. Their pulses were elevated, faces were flushed and they were speaking quickly, as if they were in a real world situation. Even nurses and faculty who had been practicing for years were not aware of the basic fact that a person with PD cannot miss their medications. This was an unforgettable experience for faculty, students and nurses, who will now always remember that a PD medication can never be withheld. Without this experience they would never have learned this lifesaving information as it relates to people living with PD.
How did your experience as an Edmond J. Safra Visiting Nurse Faculty Scholar influence this project?
Diane: It is because I am a Safra Scholar that I even knew about this funding and started to do Parkinson’s research. My previous publications with the Safra program allowed me to build the research to where it is today.
How did this study encourage intraprofessional team care?
Diane: This study promoted intraprofessional communication, collaboration and comfortability by having undergraduate students and experienced health professionals working together in a simulation safe environment.
Students in this environment were learning and performing tasks that were new to them, but doing so with trained professionals to support and provide feedback. Undergraduate nursing students could listen and learn from experienced nurse anesthesia graduate students. This simulation gave these students an increased comfort level to perform more efficiently and effectively in an actual life-threatening situation within a hospital.
What are some of the biggest challenges a person with Parkinson’s can experience in the hospital?
Diane: Parkinson’s patients are more likely to be hospitalized with complications and with decline during hospitalization. Missing medications occurs frequently in hospitalized Parkinson’s patients with increase length of stays (Martinez-Ramirez et al., 2015). Parkinson's medication errors, including missed, omitted, and delayed medications are risk factors for protracted hospital stays (Lertxundi et al 2018). Three-fourths of patients hospitalized with PD do not receive medications on time or are completely missed (Grissinger, 2018).
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Chambers, D., Sebastian, J., & Ahearn, D. (2017). Parkinson’s Disease. BJA Education 17(4), 145-149. doi:10.1093/bjaed/mkw050
Grissinger, M. (2018). Delayed administration and contraindicated drugs place hospitalized Parkinson’s Disease patients at risk. P&T 43(1), 10-11.
Gültekin, M. (2017). Medication errors increase risk of death in patients with Parkinson’s Disease. Turkish Journal of Neurology 23, 153-154. doi:10.4274/tnd.17003
Lertxundi, U., Isla, A., Ángeles Solinís, M., Domingo-Echaburu, S., Hernandez, R., Peral-Aguirregoitia, J., … García-Moncó, J. C. (2016). Medication errors in Parkinson’s Disease inpatients in the Basque Country. Parkinsonism and Related Disorders.
Lertxundi, U., Arantxa, I., Solinís, M. A., Echaburu, S. D., Hernandez, R., Peral-Aguirregoitia, J., García-Moncó, J. C. (2017). Medication errors in Parkinson's disease inpatients in the Basque Country. Parkinsonism & Related Disorders, 36, 57-62. doi:10.1016/j.parkreldis.2016.12.028
Mahajan, A., Balakrishnan, P., Patel, A., Konstantinidis, I., Nistal, D., Annapureddy, N., Sidiropoulos, C. (2016). Epidemiology of inpatient stay in Parkinson’s disease in the United States: Insights from the Nationwide Inpatient Sample. Journal of Clinical Neuroscience, 31, 162-165. doi:10.1016/j.jocn.2016.03.005
Martinez-Ramirez, D., Giugni, J. C., Little, C. S., Chapman, J. P., Ahmed, B., Monari, E., Okun, M. S. (2015). Missing dosages and neuroleptic usage may prolong length of stay in hospitalized Parkinson's disease patients. PLoS ONE, 10(4), e0124356. doi:10.1371/journal.pone.0124356.
