We always advise patients to ask their doctor what’s new in Parkinson’s disease (PD). Recently, three leading experts at the Parkinson’s Foundation Center Leadership Conference reviewed the field and updated all attendees on several of the exciting therapies currently being tested by Albert Hung, MD, PhD, Massachusetts General Hospital (MGH); Irene Richard, MD, University of Rochester Medical Center; and Hubert Fernandez, MD, Cleveland Clinic. In this month’s What’s Hot in PD blog we review their latest therapies.

There are several drugs that have been repurposed and are in clinical trials. The advantage of a repurposed drug is that it is already approved by the U.S. Federal Drug Administration (FDA). The hope for the four drugs listed below is that they will meaningfully slow disease progression.

• Isradipine (pill) is a calcium channel blocker that was previously approved for the treatment of high blood pressure. The idea behind the use of this drug is to block the entry of calcium into brain cells. Research has revealed tantalizing clues that blocking calcium may prevent brain cell death and lead to positive effects and perhaps even change disease progression.
• Exenatide (injection) is an FDA-approved diabetes drug that promotes insulin release and inhibits glucagon secretion. It is glucagon-like peptide (GLP-1) agonist. There are pre-clinical studies which show potential neuroprotective effects in toxin-based PD models.
• Nilotinib (pill) is a cancer drug used most frequently to treat leukemia. It works as a c-Abl tyrosine kinase inhibitor (blocks an enzyme). It is thought to treat the alpha-synuclein deposition that occurs in the brains of people with Parkinson.
• Inosine (pill) was a previously used drug to improve athletic performance. It is not FDA approved, but there has been great interest in using this drug to address stroke, multiple sclerosis and Parkinson’s. The idea for its use in Parkinson’s disease is that higher blood levels of uric acid may possibly decrease disease progression and this drug is effective at raising levels. The safety of the drug will be monitored especially for things like gout and kidney stones.

There is great interest in gene targeted and enzyme targeted therapies:

• GBA-associated Parkinson’s disease from the glucocerebrosidase (GBA) gene is of interest to many investigators. The pharmaceutical company Sanofi has a Phase II trial of a glucosylceramide synthase inhibitor to treat people with Parkinson’s who have the GBA gene (GZ/SAR402671).

• The gene that makes amino acid decarboxylase (AADC) and promotes conversion of brain chemicals (dopamine, serotonin) has been a target for clinical trials. There are positive interim results from an ongoing phase Ib trial and a current open-label trial.
• Ambroxol is an older drug that has been used to treat respiratory disease (decreases mucus). It also increases brain GCase activity. There are trials exploring disease modification and dementia. Allergan has a similar drug LTI-291 that may go into clinical trials soon.
• Denali has a LRRK2 inhibitor for people with the genetic mutation (LRRK2) that causes Parkinson’s. It is called DNL201. There is also a second drug DNL151 that is being tested in the Netherlands.

Finally, there is great interest in vaccine and immunotherapy trials:

• There is a vaccine trial called AFFiRiS that passed its safety testing. It is moving into the next phase to see how it will affect symptoms and disease progression.
• There are two antibody Infusion trials using intravenous injections. The current trials are Biogen (phase 2a) and Roche (phase 2b). The safety data from these trials has been promising, but there are not results of efficacy or disease modification.

We encourage all people with Parkinson’s to stay abreast of new and emerging therapies.  It is important to regularly learn about the latest Parkinson’s treatments and medications, and to check clinicaltrials.gov for the current status of ongoing research. Even if you decide a clinical trial is not for you, you may still find it useful and hopeful to monitor the latest developments in the field.

Learn more about clinical trials at Parkinson.org/ClinicalTrials.

You can find out more about our National Medical Director Dr. Michael S. Okun by visiting the Center of Excellence University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.

Each year, nurses from all over the world come together at the annual Quality and Safety Education for Nurses (QSEN) Forum to share ideas to promote quality and safety in healthcare. This year’s forum in Bonita Springs, FL, from May 30 to June 1, shined a light on Parkinson’s disease (PD) and the work being done to improve care for people living with this challenging health condition.

John Baumann, an inspirational speaker, shared his own Parkinson’s experience, giving attendees a better understanding of the patient experience. But this is not the first time Parkinson’s has been mentioned at QSEN.

In 2014, I had the good fortune of attending the Edmond J. Safra Visiting Nurse Program at the Parkinson’s Foundation in Philadelphia, PA. It was an incredibly eye-opening experience. The program consists of a 40-hour educational experience for nurses in academia and practice so that they can better understand the disease.

The program includes lectures, interactive discussions with people living with PD, clinical experience with physical therapists, time with caregivers, and several hours shadowing a physician caring for patients in a movement disorders clinic. The capstone of the experience is that participants conduct a project focused on improving care for PD patients.

The program is offered in different cities throughout the year. In 2018 the program has been hosted at the University of Toledo, Ohio; Towson University, MD; Boston University, MA; and Struthers Parkinson’s Center, MN.

Before my Edmond J. Safra Visiting Nurse Program experience I thought I understood PD, but it wasn’t until the training that I quickly realized how much I didn’t know and how misunderstood PD is. I realized that health care professionals could do a lot to improve the quality of life for people living with PD if they understood it better.

For years I served on the QSEN Institute advisory board and worked as a QSEN consultant, so for my capstone project I brought these two endeavors together: I developed an unfolding case study about a person with Parkinson’s who is admitted to the hospital for surgery. The case study emphasizes the important safety aspects of caring for patients with PD, such as the need for on-time medication administration and injury and falls prevention strategies. This unfolding case study is now published on the QSEN website and available as an educational tool for all.

Parkinson’s was prominent at this year’s QSEN Forum with presentations and posters from Edmond J. Safra Visiting Nurse Program alumni scholars who shared their innovative work that contributes to improving the quality and safety of care for PD patients. The Parkinson’s Foundation also attended the event, hosting a table with educational resources.

This annual event brings together health care professionals working to improve quality and safety for patients, but this year, it had a special meaning for all of us who care for people living with Parkinson’s. 

Article by Gerry Altmiller, EdD, APRN, ACNS-BC, Edmond J. Safra Visiting Nurse Scholar at the Parkinson’s Foundation.

Highlights from Edmond J. Safra Visiting Nurse Scholars at the Parkinson’s Foundation

Diane Ellis, MSN, RN, (front, right) clinical assistant professor, became the first nursing faculty to be awarded the distinction of Villanova Institute for Teaching and Learning (VITAL) Faculty Associate for the Fall 2018 semester. Her project, “Lost in Transition: Promoting Parkinson Patient Medication Safety,” is designed to improve care for patients with Parkinson's and includes senior undergraduate students, graduate nurse anesthesia students and clinical faculty. She is building on work with faculty colleagues Shelley Hickey, MSN, RN, clinical assistant professor (left) and Dr. Melissa O'Connor (back, center), and two research seminar students, Meghan Galvin and Addie Doyle. Professors Ellis and colleagues presented at the 2018 QSEN Forum.

Amy Bruno, PhD, RN, ANP-BC, presented “Fatigue in Parkinson’s Disease: A Qualitative Descriptive Study Exploring the Individual’s Perspective” at the 2018 American Association of Neuroscience Nurses meeting in San Diego, CA.

Orawan Kuljeerung DNP, RN, presented “Extrinsic Circumstances of Falls Among Community Dwelling Older Adults with Parkinson’s Disease: An Integrative Review” at the 2018 Annual Midwest Nursing Research Society Meeting in Cleveland, OH and at the 2018 Graduate Research Symposium in St. Louis, MO.

Denise Dion, MSN, RN, Central Arizona College, presented “A Process Improvement Project:  Nurse Faculty Approach to Improving Care Across the Continuum for patients with Parkinson’s Disease” at the 2018 QSEN Forum.

Amy Rex Smith, PhD, RN, Belhaven University, Jackson, MS, traveled to Taipei May 31-June 8, 2018 to present “The Art and Science of Spiritual Care”, work she is pursing in relationship to Parkinson’s disease.

Denise Johnson-Dawkins, DNP, MSN, RN, CNL, California State University, presented her PD simulation addressing ethics to her university’s 2018 Ethics Across the Curriculum Faculty Development Workshop.

Upcoming Programs and Webinars

Continuing education programs in Parkinson’s for nurses being held in fall 2018 as part of the Edmond J. Safra Visiting Nurse Faculty Program at the Parkinson’s Foundation include:   

• October 16 to 19: University of Alabama, Birmingham, AL
• October 25 to 26: Muhammad Ali Parkinson’s Disease Center, Phoenix, AZ
• October 31 to November 1: Weill Cornell Medicine at New York Presbyterian, New York, NY

On October 17 to 20, in Atlanta, GA, the Parkinson’s Foundation will also host the Allied Team Training for Parkinson’s (ATTP) event. All nurses who would like to continue learning about Parkinson’s and how to deliver optimal clinical care through interprofessional teams are eligible to register for ATTP.

Parkinson's disease is a chronic neurodegenerative disease that can cause a multitude of physical discomforts and psychosocial stressors. Spiritual practices may help mitigate stress and provide a source of inner strength for those with chronic diseases, yet health care workers may lack an understanding of how spirituality impacts holistic care or how to help patients in their spiritual journey. This webinar will discuss the gap that exists between PD, spiritual research and theories of uncertainty in illness as related to Parkinson’s disease. The program will explore the use of spirituality in managing PD care and provide examples of work done by nurses in this area. The webinar is led by: Diane Reynolds, EdD, RN, OCN, CNE, Former Associate Professor of Nursing, Long Island University, NY; Amy Rex Smith, PhD, RN, ACNS, BC, Professor of Nursing, Belhaven University, Jackson, MS; Lourdes Santoni, PhD, MSN, RN, CRNP- Nurse Practitioner and Educator, Northeast Center for Behavioral Health, Philadelphia, PA.

Latest Parkinson’s Research

Prior research has shown a link between moderate and severe TBI and increased risk of PD. A recently published Neurology study, “Mild TBI and risk of Parkinson’s Disease: A Chronic Effects of Neurotrauma Consortium Study,” showed that even a mild brain injury increases risk of PD in the population of veterans studied.

Immediate release amantadine has been used off label for mitigating dyskinesias in people with Parkinson’s who have fluctuations. GOCOVRI™ (ADS-5102 amantadine extended release capsules) is now available. An open label study shows an incremental reduction in baseline UPDRS Part IV scores without exacerbating adverse events.

Resource Corner

Parkinson’s Foundation Research Advocates live across the nation and are trained to assist professors teach nursing students about Parkinson’s. These advocates share their Parkinson’s experiences and advocate for PD research. If you are interested in working with a research advocate, please contact Karlin Schroeder, Parkinson’s Foundation Community Engagement Director, at KSchroeder@Parkinson.org or (800) 473-4636.

To order free Parkinson’s Foundation educational resources, please contact the Parkinson’s Foundation Helpline at 1-800-4PD-INFO (1-800-473-4636).

Over time, surgical therapies have improved treatment options for a generation of people with Parkinson’s disease (PD) who experience worsening motor fluctuations and dyskinesia. Lesion therapies, such as deep brain stimulation (DBS), are powerful options for people with these troublesome symptoms. Levodopa/carbidopa intestinal pump therapy (Duopa) provide an option for symptom relief without brain surgery. In this month’s edition of What’s Hot in Parkinson’s disease, we examine the results of the recently completed apomorphine TOLEDO pump trial, a new study examining subcutaneous apomorphine infusion (a pump therapy that delivers PD medication similar to insulin pumps for diabetes). These results may influence an individual’s decision to pursue levodopa/carbidopa intestinal gel pumps (Duopa) or deep brain stimulation.

About subcutaneous apomorphine treatment

Recently, there has been hope among the PD community that subcutaneous apomorphine treatment may  provide a less invasive option to directly address troublesome motor fluctuations. A person with Parkinson’s or a caregiver can administer the setup and procedure of a pump. A small delivery tube is placed under the skin and connected to an external pumping device filled with apomorphine. Duopa pump therapy a similar option, however is more prone to complications associated with the gastroduodenal levodopa/carbidopa gel delivery tube.

Prior to the recently published TOLEDO trial, subcutaneous apomorphine infusion had only been tested in open-label studies, which lacked control groups or the use of a placebo to more accurately test the treatment. Regina Katzenschlager, MD, and colleagues conducted a randomized placebo controlled multicenter double-blind study — the gold standard of research studies — utilizing 23 clinical trial centers across Europe and published their findings in the July issue of Lancet Neurology. 

How does the TOLEDO trial help people with Parkinson’s?

Though there were 107 people with Parkinson’s enrolled in the study, 36 did not complete the full double blind observational period. Participants had to be diagnosed at least three years prior to enrollment. Researchers were most interested in studying people with PD who have persistent motor fluctuations, despite medication. Over the course of the 12-week study, participants were randomized, some receiving three to eight milligrams per hour of apomorphine subcutaneous injections, while others received a placebo saline infusion. The infusions were only administered during waking hours — approximately 16 hours a day. The flow rates for the devices and the PD medications could be adjusted during the first four weeks of therapy. 

Apomorphine infusion improved off time by more than two hours a day; however, it surprisingly did not influence quality of life. The primary outcome variable for the study was the change in daily dopaminergic off medication time. The apomorphine infusion reduced off time compared with placebo. Data from 106 participants was analyzed. Six subjects in the apomorphine group withdrew and 44 percent had nodules (growth of tissue) where the pump was infused. The most common side effects were erythema (reddening of skin) at the infusion site, nausea and dyskinesia.

The dyskinesia scores among participants were so mild that it would be hard to judge how the apomorphine therapy would have performed if administered to moderate to severe dyskinesia cases. However, one could speculate that the apomorphine infusion would likely worsen dyskinesia as it did in 15 percent of subjects who were randomly chosen to receive the apomorphine. Finally, the four-week period where medications and apomorphine could both be simultaneously adjusted in the study, made the results difficult to evaluate. Regardless, since the study design was double blind, there was a clear benefit in improving on dopaminergic time in the apomorphine, but not in the placebo group.

What is the bottom line for the PD community? 

If you are experiencing mild to moderate Parkinson’s motor fluctuations, apomorphine infusion treatment may be beneficial — even though it is not FDA-approved in the U.S. It would make sense to try a subcutaneous apomorphine before trying the more invasive levodopa/carbidopa intestinal gel pumps or deep brain stimulation.

Unlike apomorphine infusions, both the Duopa levodopa/carbidopa intestinal gel pump and DBS have been associated with improvements in quality of life. Collectively, research suggests that both the Duopa pump and DBS approaches would have greater benefits than apomorphine infusions but have increased risks. 

Deep brain stimulation remains the most powerful treatment for severe dyskinesia. In some cases, apomorphine infusions may worsen dyskinesia. The implications of forming nodules and erythema where the pump is inserted, for short and long term apomorphine infusion treatment, remains unknown. Future and hopefully larger comparative studies can help guide people with Parkinson’s and doctors in therapy choices. 

Selected References:

Regina Katzenschlager, Werner Poewe, Olivier Rascol, Claudia Trenkwalder, Günther Deuschl, K Ray Chaudhuri, Tove Henriksen, Teus van Laar, Kevin Spivey, Senthil Vel, Harry Staines, Andrew Lees. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurology. Published online July 2018.

Okun MS. Subcutaneous Apomorphine Treatment: Results of the TOLEDO Trial. NEJM Journal Watch Neurology, 2018.

Every day, potentially groundbreaking Parkinson’s disease (PD) research ideas are explored in labs funded by the Parkinson’s Foundation. Since research never stops, I am excited to share our latest Parkinson Report newsletter with you that focuses on a topic that is critical to the Foundation and our community: research.

In this special issue, we are excited to announce four new Research Centers. These centers will receive Foundation funding dedicated to developing the latest in treatment and better understanding this disease. Read more about these centers and how we will work together to find the next PD breakthrough.

Scientists play a critical role in advancing Parkinson’s treatments. More than 500 scientists have received funding from the Parkinson’s Foundation, like James Dahlman, PhD (page 9), who conducts thousands of drug delivery tests at the same time.

In addition, learn more about the future of PD research with these articles:

• Announcing New Centers of Excellence
• Ask the Doctor: Research Edition
• PD Medications: What’s New
• Women and PD Research

We are optimistic and excited to fund the most innovative and dedicated research initiatives among those new to our field and experts, alike. It is only a matter of time until we evolve precision treatment, revolutionize therapy options and ultimately, cure Parkinson’s.

Sincerely,

James Beck, PhD
Chief Scientific Officer
Parkinson’s Foundation

Welders exposed to fumes containing low levels of the metal manganese had a high rate of Parkinson-like symptoms, which progressed with increasing cumulative exposure to the metal, according to research published in the December 28 online edition of Neurology. The results make a case for better worker protection. They also help scientists understand the underlying mechanisms by which exposure to substances in the environment may contribute to Parkinson’s disease (PD).

The law limits occupational exposure to high levels of manganese because it is known to lead to a severe movement disorder with Parkinson-like symptoms. Yet, in an earlier study, researchers led by Brad A. Racette, M.D., at the Washington University School of Medicine in St. Louis, MO, found that many welders with chronic exposure to low manganese levels had stiffness, slowness and other symptoms similar to those of PD. This is called manganism. While manganism is similar to PD in that it produces PD-like symptoms, such as slowness of movement and is characterized by a disruption of normal dopamine signaling, it is a different disease. In fact, it affects a different part of the brain than PD and not the substantia nigra.

For the new research, the scientists recruited 886 study participants who worked as welders at two Midwestern shipyards and a heavy machinery fabrication shop. Movement disorders specialists examined all participants at the start of the study and followed 398 of them for up to 10 years, using standard tests to assess Parkinson’s-like symptoms. The workers filled out questionnaires about their job types and length of employment as a basis for estimating their manganese exposure.

Results

• The average exposure to manganese was estimated to be 0.14 milligrams per cubic meter, below the legal limit of 0.2 milligrams per cubic meter.
• Of the total number of study participants, 135 (15 percent) had Parkinsonism, meaning Parkinson-like movement problems.
• Parkinson’s symptoms were progressively more severe among participants with higher cumulative manganese exposure.
• The symptoms that progressed were slowness of movement in the arms and hands, and stiffness in arms and legs, as well as speech problems and less facial expression. Symptoms tended to appear on both sides of the body (as opposed to PD which is often asymmetric).
• Welders who did flux core arc welding in a confined space, and those who were examined within the first five years of their welding experience, had the fastest progression of PD-like symptoms.

What Does It Mean?

This study is the first to report that long-term, near-threshold exposure to welding fumes containing low manganese levels can lead to progressive parkinsonism, a disease that mirrors symptoms of Parkinson’s but is a separate disease.

A strength of the study is that it followed a large number of participants over several years. Combined with research in which study participants also had brain scans, these results shed light on the mechanisms underlying manganese exposure. It remains unknown if manganese contributes to the development of PD, which is also associated with Lewy body pathology in the brain.

The study authors also advocate that steps should be taken to broadly monitor worker exposure to manganese and to reduce workplace exposure levels to below the current limits.

One year after the Parkinson’s Foundation awarded $500,000 in research grants to address critical unmet needs in Parkinson’s disease (PD), we check in with one of three of the researchers making a difference right now. 

Researchers were tasked with jumpstarting practical solutions to ease difficulties related to cognition, fatigue and sleep, all debilitating yet under-recognized symptoms in Parkinson’s. They have each received a grant funded through the Parkinson’s Foundation Community Choice Research Awards, the first program to set research priorities based on the insights of people living with Parkinson’s.

Amy W. Amara, MD, PhD, received a research grant to study "Impact of Exercise on Executive Function and Sleep" at the University of Alabama at Birmingham.

To learn more about Parkinson’s research visit Parkinson.org/Research.

One year after the Parkinson’s Foundation awarded $500,000 in research grants to address critical unmet needs in Parkinson’s disease (PD), we check in with one of three of the researchers making a difference right now. 

Researchers were tasked with jumpstarting practical solutions to ease difficulties related to cognition, fatigue and sleep, all debilitating yet under-recognized symptoms in Parkinson’s. They have each received a grant funded through the Parkinson’s Foundation Community Choice Research Awards, the first program to set research priorities based on the insights of people living with Parkinson’s.

Hengyi Rao, PhD, recieved a research grant to study "Using Brain Imaging to track Fatigue in Parkinson's Disease" at The University of Pennsylvania, a Parkinson’s Foundation Center of Excellence.

To learn more about Parkinson’s research visit Parkinson.org/Research.

When a large population of people have a disease, like Parkinson’s disease (PD), it’s essential to have accurate numbers of how many people have the disease, where they live and why they have it. In our latest research initiative, we established the Parkinson’s Prevalence Project to determine a more accurate representation of people living with PD today through a study called the Parkinson’s Foundation Prevalence Project.

The Parkinson’s Foundation Prevalence Project estimates that 930,000 people in the United States will be living with PD by the year 2020. This number will rise to 1.2 million by 2030.

"Our knowledge of Parkinson’s has changed significantly and so has our understanding of how many people have this disease,” said James Beck, PhD, Parkinson’s Foundation Chief Scientific Officer and contributing author on the study. “This study 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.”

About The Study

The Parkinson’s Foundation formed the Parkinson’s Prevalence Project in 2014 to find an accurate estimate of PD prevalence because prior estimates were widely varied. The 1978 estimate extrapolated data for how many people in the nation have Parkinson’s based on 26 cases of PD in a rural Mississippi county. The new Parkinson’s Prevalence Project estimate is nearly double the 1978 study count.

The new study sought to answer two main questions:

1. Is the prevalence of PD uniform throughout North America or does it vary by study and/or geography?
2. What will the data tell us about the prevalence of Parkinson’s and about the disease itself?

The goal of the Parkinson’s Foundation Prevalence Project is to establish the epidemiological (the incidence, distribution and control of a disease) prevalence of PD throughout North America. The study establishes a more precise estimate of PD burden through combining data from four different regions across North America: California, Minnesota, Hawaii, and Ontario, Canada. Researchers then compared these estimates to nationwide Medicare data to ensure accuracy.

The study combined data using a multi-study sampling strategy, which means large populations were divided into smaller clusters to get accurate numbers that are then applied to an entire population.

5 Facts You Should Know About the Study

1. The 2018 Prevalence Project estimate draws from large and diverse populations.
2. The new study estimate is nearly double the 1978 study prevalence number.
3. By 2020, 930,000 people in the U.S. will be living with Parkinson’s.
4. The new study confirms that men are more likely to have Parkinson’s than women and that the number of those diagnosed with PD increases with age, regardless of sex.
5. The new study found that the prevalence of people diagnosed with PD varies by region. Study researchers will devote more time to find out how.

Next Steps

Prevalence estimates of Parkinson’s will prove vital in public health planning. Updated numbers can ultimately help establish how much money and resources should go towards helping treat people with PD in each state.

“Like Alzheimer’s disease, Parkinson’s disease affects primarily older individuals and poses a significant health care burden and a real challenge on how to care for the aging population over the coming decades,” said Connie Marras, MD, PhD, lead author on the study and movement disorder neurologist at the Movement Disorders Centre at Toronto Western Hospital, Parkinson’s Foundation Center of Excellence, and the Edmond J. Safra Program in Parkinson’s research.

The Importance of the Study

Parkinson’s Foundation Prevalence Project numbers highlight the growing importance of optimizing expert Parkinson’s care and treatment for people with Parkinson’s, which would help future caregivers and ease the strain on health and elder care systems.

By supporting this study, the Foundation works to better understand Parkinson’s with the goal of solving this disease. Establishing these numbers and using them to educate PD communities and influence legislation will help the foundation provide aptly tailored resources, outreach and advocacy to the underserved PD populations across the nation.

The entire study is available and was recently published in the Parkinson’s Foundation scientific journal, npj Parkinson’s Disease.

Read more about the study and what it means for the Parkinson’s community at Parkinson.org/PrevalenceProject.

All Science News articles summarize a research study and are not an official opinion, endorsement or position of the Parkinson’s Foundation’s.

Insulin resistance (IR) is a precursor to type-2 diabetes (T2D) – a disease that occurs when your blood glucose (blood sugar) is too high. First suggested in the 1960s, a growing number of studies are finding links between Parkinson’s disease (PD) and T2D. And contrary to popular belief, you needn’t be overweight to have IR. In fact, having IR usually has no symptoms – which is why it often goes undetected. While researchers don’t fully understand what causes IR, we do know that left unmanaged, T2D can lead to serious problems such as heart disease, stroke, nerve damage, eye disease, gum disease, foot problems, bladder problems, sexual problems – and, may possibly negatively impact the course of PD. 

A recently published study in the Journal of Parkinson’s Disease titled, “High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson’s Disease” (Hogg et al., 2018), sought to determine how common IR was in non-diabetic people with PD. A battery of motor, non-motor, cognitive, and quality of life assessments were conducted. Other information gathered included height, weight, and Body Mass Index (BMI), as well as lab tests for fasting plasma insulin (the amount of insulin in your blood prior to eating a meal), fasting plasma glucose (the amount of glucose in your blood prior to eating a meal) and HbA1c (a measure used to estimate average blood glucose levels over a period of months). The study participants’ HOMA-IR was also calculated. HOMA-IR, which stands for Homeostasis Model Assessment for Insulin Resistance, is a mathematical equation that estimates steady state beta cell function (beta cells store and release insulin) and insulin sensitivity – which takes both fasting plasma insulin and fasting plasma glucose into account.

Results

• Study participants’ IR status (whether they had or didn’t have insulin resistance) did not significantly impact motor, non-motor, cognitive, or quality of life assessments in this study group.
• The HOMA-IR revealed that nearly 60% (90 out of 154 participants) of the non-diabetic study participants may have undiagnosed insulin resistance – despite having normal blood sugar levels.
• Higher BMI (being overweight or obese) was associated with increased IR.
• The HOMA-IR also revealed that a substantially higher percentage (41%) of their lean study participants had IR, as compared to healthy adults without PD.

What Does This Mean?

This study suggests that nearly two thirds of non-diabetic people with PD may be insulin resistant, despite having normal blood sugar, and in some cases, despite being lean. Thus, the big take-away from this study is that people with PD may want to have a more sensitive insulin test conducted, such as the HOMA-IR, to see if they have undiagnosed insulin resistance. There are several other IR tests as well. Which of these tests, or combinations thereof, might be best to evaluate a person’s IR is something to be discussed with one’s health care provider.

Another important take-away (although not specifically addressed in the Hogg et al. (2018) study), is that there are an increasing number of studies suggesting that IR negatively impacts dopamine functioning in the brain. Parkinson's symptoms, including tremors, stiffness, and slowness of movement, are caused by a lack of dopamine in the brain. This is particularly noteworthy for two reasons: One, the cornerstone of therapy for PD is the drug levodopa (also called L-dopa). Levodopa works by converting into dopamine and replenishing the brain's reduced supply; straight dopamine has difficulty crossing the blood/brain barrier. Two, IR is thought to precede the development of T2D by 10 to 15 years. Thus, having advanced notice of possible IR has great value, as IR is usually reversible. And while the jury is still out as to whether – and to what extent – having IR increases one’s risk for developing PD, taking proactive steps to mitigate one’s risk for developing T2D has profound long and short-term health benefits.

Learn More

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

• Substantial Matters: Episode 21: What Other Conditions Are Related to Parkinson's
• Parkinson’s Today: What’s Hot Medication Edition: Exenatide and Gocovri
• Parkinson.org: Diet & Nutrition

All Science News articles summarize a research study and are not an official opinion, endorsement or position of the Parkinson’s Foundation’s.

Usually, the first Parkinson’s disease (PD) symptom that causes people to seek medical attention is resting tremor. Three out of four people in the early Parkinson’s stages experience it. Done without conscious control or choice, a resting tremor is an involuntary, rhythmic muscle contraction that causes shaking/tremor. Most often initially detected in the hand, resting tremor may also begin in the foot or face. While the term “resting tremor” may sound benign, people with PD describe it as a symptom that is impossible to escape, socially isolating, career-ending and a constant reminder that the disease will only get worse.

Standard, first-line treatment for PD resting tremor is the combination therapy of carbidopa and levodopa. Its success rate is variable and with long-term use, commonly leads to abnormal involuntary movements called dyskinesias. Deep brain stimulation (DBS) — which involves surgically implanting small electrodes into specific brain regions — is another treatment for PD tremors. DBS delivers pulses of electricity into the brain and works like a pacemaker to help counteract abnormal brain activity in PD. Traditionally, doctors have reserved DBS for later stages of PD, when medications are no longer working and quality of life is deemed unacceptable. However, that delay in recommending DBS may be changing.

A recently published study in the journal, Neurology, titled, “Effects of deep brain stimulation on rest tremor progression in early-stage Parkinson disease” (Hacker et al., 2018), involved a post hoc analysis (an additional analysis after the study finished that was not part of the original study design) as to whether having DBS in the early stages of PD might specifically improve resting tremor.

A total of 28 people with PD (25 men, 3 women) ranging in age from 50 to 75, and with no history of dyskinesia or motor fluctuations, participated in the two-year study. Patients were randomly assigned to receive either optimal drug therapy alone (ODT), or DBS with drug therapy. A well-accepted, reliable, battery of tests designed to evaluate motor function, called the Unified Parkinson’s Disease Rating Scale–III (UPDRS-III), was conducted at baseline. The UPDRS-III was accessed on medication, and also off medication (after a one-week therapeutic washout). These on and off medication measurements were then repeated every six months for 24 months. Areas evaluated included the limbs, defined as hands, legs, and face. A participation satisfaction survey was also administered.

Results

From baseline to 24 months:

• 86% of medication-only patients developed a resting tremor in previously unaffected limbs, as compared to only 46% of patients receiving DBS and medication.
• While the total UPDRS-III scores off medication did not differ between the groups, rest tremor measured off medication was 3.1 points better for the patients receiving DBS and medication, compared to the patients receiving medication only. Rest tremor was the only measure from the UPDRS-III that showed a statistically significant improvement­ – meaning, these findings are unlikely random or due to chance, but are instead meaningful and potentially causal, i.e., DBS + medication worked better.
• Rest tremor scores measured on medication improved over the two years for the DBS and medication group, while they worsened for the medication only group. At the end of the two years, the difference between the two groups was statistically significant. 
• In the medication-only group, the average number of limbs affected by tremor doubled, whereas it decreased slightly in the DBS and medication group.
• In the patient satisfaction survey, nearly half said the greatest benefit of undergoing DBS was the management of their tremor. Note: DBS is also used for bradykinesia (slowness of movement), and rigidity.

What Does This Mean?

This Hacker et al. (2018) study suggests that having DBS in the early stages of PD may not only improve resting tremor, it may also slow the progression. The possibility of diminishing such a distressing symptom could be a game changer for those who have had to put activities, work, and interests on hold due to their tremor. As with any surgery, DBS is not without risk. This is brain surgery, involving two holes being drilled into one’s head. Serious or permanent complications are rare, but they happen.

This study does have some limitations. It was a small study, involving just 28 people. In addition, some of the analyses done were post hoc, which means they were conducted after seeing the data. In most clinical trials, the primary outcome measure (what the researcher thinks will demonstrate the greatest therapeutic benefit) is decided before the trial ever takes place. While the post hoc analysis showed an interesting relationship between DBS and slowed rest tremor progression, more studies are needed to further test this hypothesis.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. For more information on medications and deep brain stimulation, read our books Parkinson’s Disease: Medications and A Guide to Deep Brain Stimulation.

For more insights on this topic, listen to our podcast episode “What is Deep Brain Stimulation?”.