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. 

Learn more about Parkinson’s and marijuana at Parkinson.org/Marijuana.

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?
• Population: studies that involve participants in difference stages of the disease.

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. 

Learn more about Parkinson’s and marijuana at Parkinson.org/Marijuana.

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.

Recognizing and Addressing Symptoms

Non-motor PD features may also include sleep disorders, cognitive changes, hallucinations and delusions or weight changes. It’s important to stay abreast of all symptoms, and to discuss treatments with your doctor.

Read the first article in series now: Non-motor Symptoms: What’s New? Part 1.

View free resources on non-motor symptoms

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.

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’s podcast episodes:

1. 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.

Listen Now

2. 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.  

Listen Now

3. The Launch of PD GENEration
   Fall means school is in session. Learn about our latest study, PD GENEration: Mapping the Future of Parkinson’s Disease, and how it aims to help uncover key mechanisms responsible for PD and its progression.

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4. 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.

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5. 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.

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6. 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.

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7. 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).

Listen Now

If you liked what you heard, subscribe, rate and review the series on Apple podcasts or wherever you get your podcasts.

If you have any questions about the topics listed or want to leave feedback on this podcast or any other subject, you can do so here.

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).

Learn more about the Edmond J. Safra Visiting Nurse Faculty Program.

References

DiBartolo, M. (2017). Enhancing care for hospitalized patients with Parkinson's Disease: Development of a formal educational program for nursing staff. Journal of Gerontological Nursing, 43(5), 18-22. doi:10.3928/00989134-20170223-02

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.

Parkinson’s disease (PD) is neurodegenerative disorder characterized, in part, by the clumping of the protein alpha-synuclein. These clumping proteins are called Lewy Bodies that can be found in an area of the brain stem where dopamine cells die. However, we do not know exactly how the two are connected. Researchers believe that better understanding this connection would help us develop optimal targeted therapies to treat PD. 

A study published in Nature, “Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders” (Schaser et al., 2019), wondered if healthy alpha-synuclein help repair DNA damage caused by double-strand breaks (DSBs). DSBs can be the result of many things, such as environmental exposure to irradiation and other chemical agents. However, DNA damage is also a normal result of cells undergoing constant wear-and-tear. In fact, DNA damage happens in human cells thousands of times per day. Fortunately, cells repair damaged DNA on their own.

However, what if the unhealthy alpha-synuclein (which becomes Lewy Bodies) causes the loss of DSB repair, leading to healthy cells dying? While this study was not PD-specific, what if it were dopamine-producing cells that were not getting repaired and dying? The researchers conducted a series of sophisticated tests in both living mouse brains and human cells to see if this chain of events was taking place.

First, using a powerful microscope (or imaging techniques) the researchers confirmed that healthy alpha-synuclein appear exactly where the DSBs are located. However, the test did not show the cause, so further experiments were required.

Researchers then measured the amount of DSBs in healthy human cells and human cells where alpha-synuclein was completely removed (known as knock-out cells). To cause DNA breaks, they exposed the cells to a chemotherapy drug, called bleomycin. The researchers found that the cells without alpha-synuclein (knock-out cells) had higher levels of DSBs compared to healthy cells, suggesting that alpha-synuclein plays a role in repairing DSBs. They also found that the healthy human cells repaired DSBs more rapidly compared to the knock-out cells, again supporting the role of alpha-synuclein in aiding DNA repair.

Next, researchers used a strong laser, which they knew would damage the DNA and cause DSBs, to see if healthy alpha-synuclein are recruited there to help seal the breaks. They tested this in two groups of live mice and live human cells: 1. healthy and 2. Group with the disease that carry the abnormal form of alpha-synuclein. Lastly, they tried adding healthy human alpha-synuclein back into the mice without alpha-synuclein to see if it might restore the normal DNA damage response.

Results

• In both human cells in a dish (in vitro) and living mouse brains (in vivo) alpha-synuclein was present in the exact same location as the DNA repair proteins, suggesting alpha-synuclein binds directly to DSBs, and helps repair those breaks.
• In both healthy human cells and living mouse brains, the laser-induced DSBs, triggered alpha-synuclein to move to the site of DNA damage.
• In diseased human cells and mice carrying the abnormal form of alpha-synuclein, the laser-induced DSBs, impaired alpha-synuclein from moving to the site of DNA damage.
• Removing alpha-synuclein in human cells lead to increased DSB levels after receiving chemotherapy drug (bleomycin) treatment, and a reduction in the ability to repair these DSBs, compared to healthy human cells.
• Removing alpha-synuclein in mice (the knock-out mice) also resulted in increased DSBs, following bleomycin treatment.
• Giving healthy human alpha-synuclein to the alpha-synuclein knock-out mice, restored the mice cells’ DNA damage response to normal levels.

What Does This Mean?

This study suggests that the abnormal clumping of alpha-synuclein cells into the form of Lewy Bodies diminishes the available healthy alpha-synuclein to do its job of assisting in DNA damage repair (DSBs). This lack of repair triggers the cell death process, because the cell is damaged to the point where it can no longer function normally.

Of note, while this study was not designed only for Parkinson’s, these finding may offer insights as to how abnormal alpha-synuclein clumping leading to Lewy Bodies may result in the increase of cell death of dopamine-producing cells. These findings could inform the development of new PD treatments that target alpha-synuclein-mediated DNA repair mechanisms.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the Parkinson’s and LID in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).

• 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.

The dementia that many people with Parkinson’s disease develop greatly affects both those who experience it as well as their families. Parkinson’s-related dementia is associated with significant increases in illness and death compared with people who have Parkinson’s without dementia. There are currently no tests to determine which people with Parkinson’s will develop dementia and/or how quickly they will do so.

About 80% of people with Parkinson’s develop dementia by about 15 years after their PD symptoms appear. However, there is a wide variation. In some people, dementia begins as early as a few years after PD symptoms start. Other people have near-normal cognition after more than 15 to 20 years of PD motor symptoms. This difference may be related to different strains of the protein alpha-synuclein (α-synuclein), which is central to Parkinson’s.

Liana Rosenthal, MD, PhD, at Johns Hopkins University School of Medicine, received a Parkinson’s Foundation Clinical Research Award to study markers of dementia in people with PD. Her goal is to determine whether a specific, less toxic strain of α-synuclein is associated with slower progression of dementia.

To accomplish this, she will study α-synuclein from the fluid in the brain and spinal cord from people with Parkinson’s with and without dementia. Identifying progression markers for PD-related dementia, might allow us to improve the function and health of people with Parkinson’s.

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.

To have a good night’s sleep, we should work to create healthy habits and a sleep routine. Just as you brush your teeth to maintain good dental health, there are things you can do to improve nighttime sleep and daytime alertness.

Sleep-related symptoms are reported by more than 75 percent of people with Parkinson’s disease (PD). For people with PD, sleep becomes even more important as the body needs more time to restore and repair itself. The brain changes that are part of PD can also cause sleep disorders and some people have problems sleeping even before PD is diagnosed.

Getting enough sleep is essential, not just for people with PD. These seven tips can help you create healthier habits for a better sleep.

1. Set a schedule

Set a specific time to go to bed. Making this a habit will help you keep track of the hours you sleep and maintain a schedule. Going to bed and getting up at the same time helps set good sleep-wake rhythms.

2. Limit naps

If you nap, try to do so at the same time every day, for no more than an hour, and not after 3 p.m. Daytime naps may make it hard to fall and stay asleep at night. Not all naps are bad, studies have shown that short naps (lasting 15–20 minutes) may improve mood, alertness and performance on activities of daily living and other tasks. 

3. Spend time in natural light

Light helps set our internal clock. Studies have linked daytime exposure to natural light with sounder sleep. If you can’t get outdoors, consider light therapy — sitting near a light therapy box. Studies have also suggested that movement and non-movement symptoms may improve with light therapy.

4. Exercise

For people with Parkinson’s, exercise can help maintain balance, mobility and activities of daily living. Among many of its benefits, exercise promotes good sleep. After a workout, give yourself a few hours to let your body regulate its temperature, adrenaline and heart rate. Try to exercise every day and avoid exercise after 8 p.m.

5. Avoid caffeine nicotine and alcohol

While coffee can help with daytime sleepiness, caffeine and nicotine are stimulants that can cause insomnia. Avoid them in the afternoon or at night. Alcohol may help you fall asleep, but sleep can be interrupted as your body processes alcohol.

6. Relax

Getting in a relaxed mood can reduce anxiety and lead to better sleep. Make relaxation rituals a habit and listen to music or take a warm bath to settle down. Do not watch television in bed; try to use the bed for sleeping or sexual activity.

7. Regulate the bedroom temperature

A cooler temperature is better for sleep but try to avoid temperature extremes. Environments that are too cold or too warm are not conducive to good sleep. Regulating the temperature will help with your relaxation and sleeping mood.

Sleep is a critical topic of interest for the PD community, which is why the Parkinson’s Foundation has multiple resources dedicated to address it:

• Sleep: A Mind Guide to Parkinson’s Disease
• Episode 46: Addressing Sleep Discomfort with Parkinson’s
• Sleep Disorders

Together, we made life better for people in our Parkinson’s community in 2019. Your support allowed us to launch new, exciting initiatives that are changing lives, while funding critical research and local classes tailored to people with Parkinson’s disease (PD). With your support, we are reaching more people living with this disease in the U.S. and are closing the gap to help the 60,000 Americans diagnosed every year.

Thanks to YOU, we were able to accomplish the following in 2019:

1. Launched First-of-its-Kind Free Genetic Testing Initiative
   We launched PD GENEration: Mapping the Future of Parkinson’s Disease, a national initiative that offers free genetic testing for clinically relevant PD-related genes and free genetic counseling. We are excited to reach our goal of testing and providing genetic counseling for up to 15,000 people with PD.
    
2. Funded $12.2 Million to Further Parkinson’s Research
   This was an impactful year for Parkinson’s research. We established four new Research Centers that will receive a total of $8 million to launch PD-specific research studies. We also  simultaneously funded $4.2 million across 46 research grants that support the work of promising scientists in the PD field, cutting-edge clinical trials and fellowships.
    
3. Designed Program for People Newly Diagnosed with Parkinson’s
   With a focus to reach the 60,000 people who are newly diagnosed with PD each year in the U.S., Newly Diagnosed: Building a Better Life with Parkinson's Disease aims to close the gap between diagnosis and knowing where and how to find the right information and resources to live better with PD. Order or download the free Newly Diagnosed kit. 

4. Shared Research Findings at the 5th World Parkinson Congress
   In June, we enthusiastically joined our international community at the 5th World Parkinson Congress (WPC) in Kyoto, Japan, where our PD experts shared 10 research posters.
    
5. Expanded our Centers of Excellence Care Network
   Every year, we hope to bring expert care to more people with PD. In 2019, we expanded our Center of Excellence global network to include three new centers. Centers of Excellence are a medical center with a specialized team who provide expert Parkinson’s care. Find a Center of Excellence in your area.
    
6. Partnered with Michael J. Fox Foundation for Parkinson’s Research to Report New Economic Burden and Host Policy Forum
   In 2019, we collaborated with the Michael J. Fox Foundation (MJFF) to publish that the economic burden of Parkinson’s is nearly $52 billion every year. Together, we also hosted the 2019 Parkinson’s Policy Forum, bringing more than 150 advocates from across the U.S., along with leading experts in PD research to advocate for our community.
    

7. 

   Granted $1.5 Million to Local Communities for Parkinson’s Programs
   We proudly funded $1.5 million throughout 118 community-based grants that provide education and outreach programs, along with local research initiatives, that address unmet needs in the PD community.

8. Issued First Patient-Centered Research Agenda for Women with PD
   Recognizing long-standing gender disparities in Parkinson’s research and care, our Women and Parkinson’s Initiative created the first patient-centered action agenda to maximize quality of life for women with Parkinson’s.
    
9. Appointed Aware in Care Ambassadors
   In 2019, we appointed our first-ever  Aware in Care Ambassadors, a volunteer group to help distribute Aware in Care kits that serve to bolster best practices in treating patients with Parkinson’s disease to both patients and healthcare providers.
    
10. Designed New Online Nurse Course
    With the prevalence of PD expected to increase in the coming years, we wanted to provide more professional education opportunities for nurses. In 2019, we launched a new online course for nurses who deliver care throughout all stages of Parkinson’s. 

As much as we accomplished in 2019, we are committed to furthering our reach and impact in 2020 to help even more people live better with Parkinson’s. Your continued support is the only way we can make that happen. Thank you.