In 2011, the FDA approved a diagnostic test for Parkinson’s disease. The DaTscan (Ioflupane I 123 injection, also known as phenyltropane) is a radiopharmaceutical agent which is injected into a patient’s veins in a procedure referred to as SPECT imaging. DaTscan, when it was approved, was considered an important addition to the armamentarium of the bedside clinician. In 2011 I wrote a What’s Hot column on DAT scanning, and this month I will update that posting and bring everyone up to date on the impact of this test.

One of the most frequently asked questions about Parkinson’s disease is whether or not to pursue DaT or PET scan to confirm a diagnosis of Parkinson’s disease. The short answer is that the DaT test is over-used in clinical practice, and is only FDA approved to distinguish potential Parkinson’s disease from essential tremor. In fact, the test only tells the clinician if there is an abnormality in the dopamine transporter, and does not actually diagnose Parkinson’s disease (could be parkinsonism). PET is also overused, though it can be a more powerful diagnostic tool when in the right expert hands.

If you have already received a diagnosis from an expert, and are responding well to dopaminergic therapy, in most cases of Parkinson’s disease, PET and DaT scans would not add any new information, and may prove unnecessary. In cases where the expert is not sure of the diagnosis – is it essential tremor or Parkinson’s, for example-- or where a potentially risky procedure is being considered (e.g. deep brain stimulation surgery), it is reasonable for your doctor to recommend a PETscan or DaTscan. It is important to keep in mind that PET and DaT scans should be performed only by experienced neurologists who have executed a large volume of Parkinson’s disease scans, because experience is important in accurately reading the imaging results. One important update is that DAT scans can and have been misread since the FDA approval in 2011. The reason DAT scans can be misread is because the interpretation is performed entirely by the eye (there are no hard numbers to make the diagnosis). This type of “qualitative” interpretation is subject to error. We always recommend that the interpretation be performed in the context of the clinical symptoms of the patient, and when in doubt to get a second opinion from a Parkinson’s expert.

Here is how the scanning process works for DaT: First, the PD patient receives an injection of the imaging agent. After injection, the compound can be visualized by a special detector called a gamma camera. This scan measures something called the dopamine transporter (DaT), and it can help a doctor determine if patients are suffering from essential tremor vs. Parkinson’s disease or another parkinsonism (i.e., other problems affecting dopamine systems that have symptoms that look like Parkinson’s disease). The side effects if they occur are minimal (e.g. headache, dizziness, increased appetite and creepy crawly feeling under the skin). PET scans and DaT/SPECT scans examine the "function" of the brain, rather than its anatomy (appearance). This is an important point because unlike in strokes and tumors, the brain anatomy of a Parkinson’s disease patient is largely normal. These scans can reveal changes in brain chemistry, such as a decrease in dopamine, which may help identify Parkinson’s disease and other kinds of parkinsonism. There are several compounds available for use in both PET and SPECT scanning; however PET scans typically focus on glucose (sugar) metabolism, and DaT/SPECT scans focus on the activity of the dopamine transporter. 

The new DaT scans use a substance that "tags" a part of a neuron in the brain where dopamine attaches to it, thus showing the density of healthy dopamine neurons. Thus, the more of the picture that "lights up", the more surviving brain cells. Dark areas could mean either Parkinson’s disease or parkinsonism.

In Parkinson’s disease, people will lose cells in a part of the brain associated with movement referred to as the basal ganglia. There is a common pattern seen in people with Parkinson’s, with the cell loss starting on just one side, towards the back of the basal ganglia. Over time, the affected area spreads across the entire region. However, as part of the typical aging process, it is normal to lose some of these cells—therefore it takes an expert to read these scans and figure out if the changes are due to normal aging or due to disease. There are typical scan patterns that may emerge. The more widespread the decrease in uptake on the scan, the more advanced the degeneration.

Interpretations of DaT scans can be tricky. The first determination is whether the scan is normal or abnormal. Next, the expert will determine if the scan follows the pattern of Parkinson’s disease or parkinsonism. Finally, a determination will be made as to the severity of the brain cell loss.

PET scans are FDA-approved for the diagnosis of dementia, but not for the diagnosis of Parkinson’s disease. However, if you or your relative has cognitive impairment, the scan can be ordered to examine for the presence of Alzheimer’s changes, as Parkinson’s disease can co-occurs with Alzheimer’s. The cost of a PET scan ranges from $2,500-5,000. Many expert centers perform PET scans for free under research protocols.

Recently, in studies that have attempted to diagnose Parkinson’s early in its course, researchers have found that a subset of patients thought to have Parkinson’s disease have turned up with negative PET or DaT scans. These patients do not seem to develop the progressive symptoms of Parkinson’s disease. The findings are humbling, and they lend credence to the importance of following patients over long periods of time to ensure both accurate diagnosis, and also appropriate treatment. 

An example DaTscan is shown below and it demonstrates essential tremor on the left (normal DaT), and a parkinsonian syndrome on the right (decreased DaT).

An example of a PET scan is below and it reveals: in the top panel a normal scan, in the middle panel abnormalities in the putamen (red uptake in the figure) in a patient with Parkinson’s disease, and in the lower panel a return to an almost normal scan following the introduction of levodopa.

In conclusion, in cases where the diagnosis is uncertain (e.g. Parkinson’s disease versus essential tremor), a DaT or PET scan can be very useful. Patients and their families need to be aware that in general, these scans cannot reliably separate Parkinson’s disease from parkinsonism (multiple system atrophy, corticobasal degeneration, progressive supranuclearpalsy), and thus if you seek a scan you will still need an expert to sort out your clinical picture and eventual diagnosis. If you have already been diagnosed, and your symptoms are progressing, and you have an adequate response to medications, a PET or DaTscan will add little new information and therefore will not be necessary. A scan should never replace a clinical examination, and findings should be correlated to the symptoms of an individual patient. Since the interpretation of these scans is often qualitative (by the eye, especially with DaT), a second opinion in uncertain cases can be helpful.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also 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 and 10 Breakthrough Therapies for Parkinson's Disease.

One of the most common questions that we receive on the 1-800-4PD-INFO Helpline is “when should I start medications for my Parkinson’s disease.” This months What’s Hot in PD column will focus on this simple, but critically important question.

The most important factor in initiating medications for an individual patient is whether Parkinson’s symptoms are affecting quality of life, or alternatively whether symptoms are affecting work performance. Bothersome Parkinson’s symptoms commonly include motor issues (tremor, stiffness, slowness, walking, and balance problems), and/or non-motor issues (depression, anxiety, sexual dysfunction, other issues). Most experts agree that there is no benefit to delaying medication therapy if bothersome symptoms appear, and there may be risks in delaying treatment, especially if a treatment delay results in unsteadiness, falls, and fractures.

Over the last 10-20 years the thinking has evolved on when and how to initiate medication therapy for early Parkinson’s disease. Most experts agree that the medication dosage and the timing of the medication dosage should be carefully monitored in order to maximize the control of potentially responsive Parkinson related symptoms. The recommendation that patients should be started on dopamine agonist instead of levodopa (Sinemet) has faded over the last decade, especially with the emergence of impulse control disorders and other dopamine agonist associated side effects.

The best advice we can offer Parkinson’s disease patients is to not fear treatment, and to especially not fear dopaminergic therapy. Sinemet and other Parkinson’s therapies have not been shown to be toxic or to accelerate disease progression. Dopamimergics never “stop working,” however they may require adjustment over time. If Parkinson’s disease symptoms are affecting quality of life, the work performance, or if there exists a risk of falling, treatment should be initiated. Many practitioners will start with a MAO-B drug (selegiline, rasagiline, dissolvable selegiline, other), but Parkinson’s patients should be aware that the symptomatic effects of MAO-B’s are extremely mild. It is in fact rare to remain on this drug without other Parkinson’s drugs for any significant period of time. Dopamine agonists (ropinerole, pramipexole, cabergoline, rotigotine, others) and levodopa (Sinemet, Madopar) are both excellent choices for early Parkinson’s disease therapy. The choice of agent should however, consider the individual’s comprehensive medical picture (age, co-morbidities, types of symptoms, history of neurological/psychiatric issues) as therapy should never be viewed as a “one size fits all.” Finally, patients should remember that if depression, anxiety and other issues persist following dopaminergic treatment, then antidepressant therapy may also be warranted. 

Other drugs such as amantadine may be used early in Parkinson’s disease therapy, however most practitioners reserve amantadine for treatment ofdyskinesia which may or may not occur later in the disease course. Patients should keep in mind that exercise is like a drug, and that a daily routine is often a great symptomatic supplement to any medication regimen. Many practitioners wait to utilize physical therapy, occupational therapy, and speech therapy later in the disease, however these modalities can often be powerful treatments when employed early in the disease. Finally, all Parkinson’s disease patients should have a general practitioner and a dermatologist involved with their care. The reason for involving “other doctors” is because with adequate Parkinson’s treatment, they will be far more likely to encounter difficulties with other medical illnesses (heart disease, prostate cancer, breast cancer, melanoma, etc.). Melanoma occurs more frequently in Parkinson’s disease populations.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also 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 and 10 Breakthrough Therapies for Parkinson's Disease.

This past month, the FDA approved DaTscan (Ioflupane I 123 injection, also known as phenyltropane), a radiopharmaceutical agent which is injected into a person's veins in a procedure referred to as SPECT imaging. DaTscan is an important addition because it is anticipated to be more widely available than other techniques and it has received several major endorsements from leading scientists.

One of the most frequently asked questions about Parkinson's disease (PD) we receive is whether or not to pursue DaT or PET scanning to confirm a diagnosis of Parkinson’s disease. In this month’s What’s Hot column, we offer a review of the subject in light of the recent FDA approval.

If you have already received a diagnosis from an expert, and are responding well to dopaminergic therapy, in most cases of Parkinson’s disease, PET and SPECT scans would not add any new information and therefore likely to be unnecessary. In cases where the expert is not sure of the diagnosis — is it essential tremor or Parkinson’s, for example — or where a potentially risky procedure is being considered (e.g. deep brain stimulation surgery), it is reasonable for your doctor to recommend a PETscan or DaTscan. 

It is important to keep in mind that PET and SPECT scans should be performed only by experienced neurologists who have executed a large volume of Parkinson’s disease scans, because experience is important in accurately reading these imaging results.

Here is how it works:   

First, the person receives an injection of the imaging agent. After injection, the compound can be visualized by a special detector called a gamma camera. This scan measures something called the dopamine transporter (DaT), and it can help a doctor determine if patients are experiencing essential tremor, vs. Parkinson’s disease or another parkinsonism (i.e., other problems affecting dopamine systems that have symptoms of Parkinson’s disease). The side effects are minimal (e.g. headache, dizziness, increased appetite and creepy crawly feeling under the skin).

PET scans and DaT/SPECT scans examine the "function" of the brain rather than its anatomy.

This is an important point because unlike in strokes and tumors, the brain anatomy of a person with Parkinson’s disease is largely normal. These scans can show changes in brain chemistry, such as a decrease in dopamine, which identify Parkinson’s disease and other kinds of parkinsonism. There are several compounds available for use in both PET and SPECT scanning; however PET scans typically focus on glucose (sugar) metabolism, and DaT/SPECT scans focus on the activity of the dopamine transporter.

The new DaT scans use a substance that "tags" a part of a neuron in the brain where dopamine attaches to it, showing the density of healthy dopamine neurons.  Thus, the more of the picture that "lights up", the more surviving brain cells. If the parts of the brain where dopamine cells should remain dark in the scan, an expert reader may diagnose early brain degeneration.  This could mean either Parkinson’s disease or parkinsonism.

In Parkinson’s disease, people will lose cells in a part of the brain associated with movement referred to as the basal ganglia. There is a common pattern seen in people with Parkinson’s, with the cell loss starting on just one side, towards the back of the basal ganglia, and deep down.  Over time, the affected area spreads across the basal ganglia. However, as part of the normal aging process, it is completely normal to lose some of these cells — therefore it takes an expert to read these scans and figure out if the changes are due to normal aging or due to disease. There are typical scan patterns that may emerge. The more widespread the decrease in uptake on the scan, the more advanced the degeneration.

Interpretations can, however, be tricky.  The first determination is whether the scan is normal or abnormal.  Next, the expert will determine if the scan follows the pattern of Parkinson’s disease.  Finally, a determination will be made as to the severity of the brain cell loss.  There are only a few centers that regularly perform very high-quality PET scans for Parkinson’s disease, and these centers usually have experts in interpretation. Two centers with leading reputations include Long Island Jewish Hospital in New York (North Shore) and Washington University Hospital in St. Louis, although there are others.

PET scans are FDA-approved for the diagnosis of dementia, but not for the diagnosis of Parkinson’s disease. However, if you or your relative has cognitive impairment, the scan can be ordered to examine for the presence of Alzheimer’s changes as Parkinson’s disease often co-occurs with Alzheimer’s. The cost can range from $2,500-5,000.  Many expert centers perform PET scans for free under research protocols.

Recently, in studies that have attempted to diagnose Parkinson’s early in its course, researchers have found that a subset of people thought to have Parkinson’s disease have turned up with negative PET or SPECT scans. These people do not seem to develop the progressive symptoms of Parkinson’s. These findings are humbling, and they lend credence to the importance of following people over long periods of time to ensure both accurate diagnosis, and also appropriate treatment. 

An example DaTscan is shown below and it demonstrates essential tremor on the left (normal DaT), and a parkinsonian syndrome on the right (decreased DaT).   

An example of a PET scan is below and it reveals: in the top panel a normal scan, in the middle panel abnormalities in the putamen (red uptake in the figure) in a person with Parkinson’s, and in the lower panel a return to an almost normal scan following the introduction of levodopa.  

Conclusion

In cases where the diagnosis is uncertain (e.g. Parkinson’s disease versus essential tremor), a DaT or PET scan can be very useful. 

People with Parkinson's and their families need to be aware that in general, these scans cannot reliably separate Parkinson’s disease from parkinsonism (multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy), and thus if you seek a scan you will still need an expert to sort out your clinical picture and diagnosis. If you have already been diagnosed, if your symptoms are progressing, and you have an adequate response to medications, most likely a PET or DaTscan would add little new information and therefore not be necessary.

Conclusion

Explore these Parkinson's Foundation resources:

• 10 Early Signs of Parkinson's
• Getting Diagnosed
• Living with Parkinson's

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also 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 and 10 Breakthrough Therapies for Parkinson's Disease.

People with Parkinson’s disease (PD) are in critical need of new, more effective therapies to treat the symptoms of the disease like dyskinesia and to stop its progression.

Currently, an anti-viral drug called amantadine is used off label to treat dyskinesia — episodes of involuntary movements of the arms, legs and head. But amantadine carries risk of side effects such as insomnia and hallucinations.

Fortunately, the U.S. Food and Drug Administration (FDA) approved Gocovri, an extended release amantadine preparation, to treat dyskinesia. It is the first drug FDA approved for this specific purpose. According to one randomized double-blinded and placebo-controlled study (the gold standard of research), patients who received Gocovri experienced improvements in their symptoms. Subjects were followed for six months. When patients were evaluated using the Unified Dyskinesia Rating Scale, a clinical scale for measuring response to therapies, the Gocovri group gained eight points over those in the placebo group. And two other recently published studies have confirmed the benefits of Gocovri for the treatment of dyskinesia.

Here’s What You Need to Know

Gocovri is a one-a-day treatment designed to limit side effects. However, because no head-to-head test of generic amantadine versus Gocovri has been done, we do not know whether this new formulation is more effective. Still, many studies show that amantadine — in any formulation —can be effective in suppressing dyskinesia. A recent Parkinson’s Foundation study found that regular release amantadine alleviated dyskinesia.

Overall, patients who are doing well on multiple doses per day of generic amantadine will likely not benefit from switching to one-a-day Gocovri. However, those experiencing side effects from amantadine now have another option. It could provide a one-a-day solution to dyskinesia that previously could only be managed with multiple doses per day.

A Diabetes Drug to Treat Parkinson’s

Recently a small study published in the journal Lancet suggested that Exenatide, a medication used to manage diabetes (more specifically, a glucagon-like peptide-1 receptor stimulator) may slow the progression of Parkinson’s. Exenatide is being studied as a neuroprotective pharmacological treatment for people living with Parkinson’s.

Exenatide has shown neuroprotective benefits in animal models, but not in humans. To see if this diabetes therapy has disease-modifying effects in people with Parkinson’s, British investigators performed a double-blind, placebo-controlled study on 62 patients. Of those, 30 received two-milligram injections of Exenatide, and 32 received a placebo once a week for four months. Both groups then stopped the study drugs for three months for what is called a “wash out” period.

The primary outcome was an improvement of motor symptoms, as measured on the Unified Parkinson Disease Rating Scale (a scale used in clinical studies to measure behavior, activities of daily life, motor symptoms and other components over the course of PD). A Parkinson’s motor score was calculated at the beginning of the study and after the intervention. Study results showed an improvement of one point on the Unified Parkinson Disease Rating Scale among the Exenatide group, and a decline of 2.1 in the placebo group.

Here’s What You Need to Know

This is an exciting finding suggesting Exenatide provides some neuro-protection to people with Parkinson’s. However, because the results of this small study are preliminary, there is not enough data to prove neuro-protection. The bottom line is that Exenatide is a promising drug, but larger trials are needed to determine if it indeed has disease modifying effects in people with Parkinson’s. 

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

JAMA Neurology, “Viewpoint”, 11/13/17

Authors: E. Ray Dorsey, MD, Department of Neurology, University of Rochester Medical Center, Rochester, NY; and Bastiaan R. Bloem, MD, PhD, Radboud University Medical Center, Department of Neurology, Nijmegen, the Netherlands.

In June 2017, the Parkinson’s Foundation brought together the thought leaders in the Parkinson’s community to discuss the future of Parkinson’s research at an event called, “World Without Parkinson’s” in New York City. At this event, Drs. Dorsey and Bloem stressed the importance of caring for people with Parkinson’s today, and the increasing need for systems to extend the reach and expand the scale of care.  They asked the audience: How can we shift the paradigm within the health care system to be more patient-focused?

People are at the heart of the issue.  At the World Without Parkinson’s event, Drs. Dorsey and Bloem pointed out that if you look at how public health and healthcare are changing lifespans around the world, the resulting growth in the over 65 population will effectively result in a pandemic of Parkinson’s disease. They have now published in JAMA Neurology, a major scientific journal, an opinion piece issuing a clarion call to action to make the voices of the Parkinson’s community heard. They pose the question: if the worldwide number of people with Parkinson’s disease (PD) will double from 6.9 million in 2015 to 14.2 million in 2040, do our efforts reflect the urgency commensurate with the challenge?  What are we doing to treat these millions of individuals to lead healthy lives?  They write that increasing access to care and increasing funds for Parkinson’s research are the answer.

For decades, the Parkinson’s Foundation has been educating and empowering people living with Parkinson’s and their families. We are at the forefront of improving lives for people with Parkinson’s today.  Starting with our focus on today’s patients through the first Parkinson’s advisory council and people with PD research training program, we have extended this vision to include the Parkinson’s Outcomes Project, the largest clinical study of Parkinson’s ever conducted and the only major study with a singular focus on how to improve the lives of everyone living with Parkinson’s today. We ensure better care through our global network of 42 Centers of Excellence and we work to close the gaps in Parkinson’s care by training doctors, nurses, physical therapists, speech language therapists and social workers so they can provide better care to their Parkinson’s patients across the nation and around the world.

We will remain at the forefront of addressing disparities in Parkinson’s care and engaging patients to advocate for better care. As Parkinson’s reaches epidemic-like proportions, it’s clear that this work is more important than ever. We will continue to invest in research and improving lives until a world without Parkinson’s is in reach.

#WorldWithoutParkinsons

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.

Milton Biagioni, MD, received a research grant to study the "At-home Non-Invasive Brain Stimulation for Fatigue and Cognitive Slowing" at The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone, a Parkinson’s Foundation Center of Excellence. 

Q: Can you explain your study in less than 100 words?

A: I am studying the likelihood and usefulness of a portable, non-invasive, brain stimulation device to alleviate fatigue and cognitive slowing in people with Parkinson’s. These are two of the most prevalent symptoms responsible for disability and for reducing quality of life in people with PD. To date there are no proven effective treatments available for either symptom. In this study we use a specially designed transcranial direct current stimulator (tDCS) device through a new method of remote supervision. The therapy is done in the participant’s home through video-conferencing.

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

A recent study by Inga and colleagues at the Mount Sinai Beth Israel Parkinson’s Foundation Center of Excellence in New York examined the incidence of Parkinson’s disease in inflammatory bowel disease patients. The authors were also interested as to whether exposure to anti-tumor necrosis factor therapy (anti-TNF) could possibly reduce the risk of the later development of Parkinson’s disease. In this month’s What’s Hot in PD? blog we will discuss the links between inflammatory bowel disease and also examine the intriguing possibility that anti-TNF or related approaches may one day be used as Parkinson’s disease treatments.

The idea that inflammation is an important factor in the development of Parkinson’s disease is not new and systemic inflammatory diseases may provide an important clue to pathogenesis. There are almost two million people in the United States suffering from inflammatory bowel disease and there has been great interest in its potential links to neurodegeneration. The LRRK2 (leucine-rich repeat kinase 2) gene is a well-established risk factor for Parkinson’s disease. LRRK2 has also been strongly linked to Crohn’s disease, and this link has raised the question as to whether there is a relationship between inflammatory bowel and Parkinson’s disease. Ulcerative colitis is the other common inflammatory bowel disease, and although much less is known about its links to Parkinson’s disease there has been recent interest in exploring this area. Many inflammatory bowel disease studies include both Crohn’s disease and ulcerative colitis patients.

Inga and colleagues, in a recent issue of JAMA Neurology, examined administrative health insurance claims from approximately 170 million people (Truven Health MarketScan administrative claims database and the Medicare Supplemental Database) and observed that inflammatory bowel disease patients were 28% more likely to develop Parkinson’s disease. Even more intriguing was the observation that exposure to anti-TNF therapy was associated with a 78% reduction in Parkinson disease incidence.

Though the studies were observational and the results derived from analysis of data from health insurance claims, the idea that systemic inflammation plays a key role in Parkinson’s disease is intriguing. Anti-TNF or other anti-inflammatory therapies may be candidates for future clinical trials.

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.

In addition to being a movement disorder specialist at the University of Pennsylvania Movement Disorder Center, a Parkinson’s Foundation Center of Excellence, Allison Willis, MD, is also one of the few researchers to conduct much-needed Parkinson’s disease (PD) research on one of the most vulnerable populations within the Parkinson’s community: women.

Vulnerable: underserved populations that are not accessing or cannot access healthcare services for their disease. This may be due to: a shortage of healthcare professionals and/or supplies, healthcare failures in their area, in addition to personal barriers, such as socio-economic status, cultural or linguistic differences.

“We know that people with Parkinson’s are physically, psychologically and socially vulnerable,” Dr. Willis said. What researchers, including Dr. Willis, are discovering is that women with Parkinson’s are uniquely vulnerable and do not receive the same advocacy or care as other vulnerable populations with Parkinson’s.

Dr. Willis conducts her research using a wide range of data, concentrating on the healthcare outcomes and differences in people with neurological diseases. One of her primary sources is the Parkinson’s Foundation Parkinson’s Outcomes Project, the largest clinical study of PD that tracks over 12,000 people with Parkinson’s.

In general, women have an overall lower risk of being diagnosed with Parkinson’s than men. This resilience to the disease might be because of a natural protection estrogen provides in the brain or by another hormone not yet known. However, the total number of women living with PD is not far behind that of men, because, on average, women live longer than men.

Studies show that women who are diagnosed with Parkinson’s face more struggles throughout the course of their disease than their male counterparts. As Dr. Willis phrases it, the “female paradox” relates to Parkinson’s in that women might be more protected biologically, but usually have a tougher PD journey. Women with PD are more likely to:

• have side effects from their Parkinson’s medications.
• not receive social support.
• have overwhelmed care partners, requiring outside, paid caregiving.

This paradox receives little attention in PD research, but Dr. Willis works every day to address it. “Parkinson’s research studies are overwhelmingly male, and we generally think that’s because men have a higher risk,” Dr. Willis said. “We really need to think carefully about why we have so few women involved in research when there are actually a lot of women who are being diagnosed with Parkinson’s, they’re just not being directed to our centers for research.”

Many scientists do not actually treat the disease they study firsthand. But Dr. Willis directly ties her research to her patients, spending 80 percent of her time conducting research and the other 20 percent with her Parkinson’s patients. “When I’m doing research, I’m thinking about my patients and how they inform my research,” she said.

This might explain why scientists do not actively focus on the female paradox and, consequently, why healthcare systems and policies reflect this lack of attention. Through her research, Dr. Willis tries to bridge the gap between the people with the disease, researchers and those who create the policies that affect the PD community.

The Patient-Centered Outcomes Research Institute (PCORI) awarded a grant to the Parkinson’s Foundation for the development of Women and PD Teams to Advance Learning and Knowledge (Women and PD TALK), which Dr. Willis helps manage. This project will help develop new patient-centered recommendations to improve the health of women living with Parkinson’s.

“Parkinson’s research needs to be restructured to be all-inclusive from the beginning,” Dr. Willis said. “Women need to be receiving the necessary care and attention throughout the progression of their disease, before onset and by a multitude of people.”

Women and PD TALK, which will soon host its tenth forum where women with PD, care partners and other medical professionals come together to discuss risks, symptoms, treatments and care from the perspective of women with PD. Dr. Willis has high hopes for the upcoming fall leadership forum to develop national recommendations based on these regional findings.

"I envision a round table with a female clinician scientist, a female PD patient, their caregiver, an allied healthcare worker, physical therapist and social worker all talking about how to bring ideas together and develop research projects that Congress will listen to, especially when they consider physical therapy or home health assistance for women with PD," Dr. Willis said.

These forums have laid the groundwork for a national network of women researchers, clinicians and women with PD who are committed to disseminating and utilizing the findings of the Women and PD TALK project to improve research and care for women with Parkinson’s.

It is Dr. Willis’ goal for research projects like Women and PD TALK and her hope for the future of healthcare systems to represent everyone with Parkinson’s disease. Improved studies about why women have a lower risk of PD, can result in lowered risk or prevention for everyone. Researching why and what can be done about failed caregiving for women with PD, can in turn improve caregiving for everyone.

“Figuring out how and why the experiences of women differ has benefits for every single person who has Parkinson’s disease and the people who haven’t developed it yet,” Dr. Willis said

The University of Pennsylvania Movement Disorder Center is located in Philadelphia, PA. Learn more about the nearest Parkinson’s Foundation Center of Excellence at Parkinson.org/search.

Learn More about Women & Parkinson's

People with Parkinson’s disease (PD) and their physicians are both looking to answer whether medical marijuana can help manage Parkinson’s symptoms. Researchers have barely scratched the surface when it comes to marijuana and PD and previous studies are inconclusive about its potential benefits, but many people with Parkinson’s are curious to try it. Here’s what you need to know.

The following article is based on the latest research and a Parkinson’s Foundation Expert Briefings about marijuana and Parkinson’s hosted by Benzi M. Kluger, MD, MS, Associate Professor at Neurology and Psychiatry at University of Colorado.

What’s in Marijuana?

Marijuana itself — the dried leaves known by names like pot and weed — comes from a genus of flowering plants called Cannabis. Cannabis plants contain more than 100 chemicals, called cannabinoids, which affect the human nervous system. Some of these chemicals stimulate parts of the brain, while others block the same effects.

The best-known plant-based cannabinoids are:

• THC (D9-tetrahydrocannabinol): the psychoactive component of Cannabis responsible for making a person feel “high.” Sativa strains of Cannabis (Cannabis sativa) tend to have higher THC concentrations than others. Marijuana available today typically has 10 to 30 times the amount of THC as that from the 1970s.
• CBD (cannabidiol): the component of cannabis that may have calming effects on the nervous system. It does not have the psychoactive effects of THC. The indica and rudaralis strains of Cannabis (Cannabis indica and Cannabis rudaralis) tend to have less THC and more CBD.

Marijuana Research

Endorphins are the naturally occurring substances in the brain that help reduce pain. They are boosted by exercise. Sometimes they are called the brain’s natural opiates, because opioid drugs bind to the same cell receptors as endorphins. Similarly, the brain has its own naturally occurring cannabinoids. Cannabinoids in marijuana have an effect by binding to the receptors for these natural molecules.

The chemicals in the brain that are similar to the active agents in marijuana are called endocannabinoids. Of these, scientists have studied anandamide, which may play a role in pain, sleep and other behaviors, along with the development of the nervous system. The name anandamide means “bliss.” This chemical is found in the human brain and, not surprisingly, in chocolate.

Do endocannabinoids have a role in Parkinson’s? Researchers know that they are involved in the brain area called the basal ganglia, which is affected by PD. Through research, scientists are gaining an understanding of the two main receptors in the brain that respond to marijuana:

• CB1 (primarily in the central nervous system)
• CB2 (primarily in the immune system).

The dozens of different cannabinoids in marijuana have a range of effects to activate or block receptors. 

In studies with laboratory animals, cannabinoids that bind to CB1 have been reported to improve dyskinesias, the involuntary movements that can develop after several years of taking levodopa therapy. Cannabinoids also have antioxidant and anti-inflammatory effects, which could point to neuroprotective activity. Some studies support this idea, but more research is needed.

Cannabinoids synthesized in the laboratory (rather than extracted from marijuana) have been tested as therapies for diseases other than Parkinson’s. CBD recently was approved as a therapy for rare types of epilepsy. Two synthetic cannabinoids are sold as FDA-approved therapies for nausea and other side effects of cancer chemotherapy:

• Marinol (dronabiol): synthetic THC
• Nabilone: a cannabinoid that acts on both CB1 and CB2

Warning: Synthetic Marijuana

Synthetic marijuana, sold legally under names such as K2 and Spice, contains lab-made cannabinoids and other chemicals. Synthetic marijuana can cause severe, even deadly, side effects. It is not a substitute for plant-based marijuana and remains unregulated.

Clinical Studies

Few studies have enrolled people with PD to investigate the effects of cannabinoids on Parkinson’s symptoms. So far, the most rigorous clinical studies of cannabis and PD movement symptoms have been inconclusive at best, because of the small numbers of participants and other limitations.

In other, less rigorous studies, researchers have surveyed cannabis use among people with Parkinson’s. In these surveys people reported their own experiences, without comparison to a control group. Small numbers of participants reported that cannabis helped tremor, slowness, and non-motor symptoms such as pain, sleep difficulties, anxiety and loss of appetite.

Research is under way to better understand how specific cannabinoids might affect PD symptoms, including a study of the safety and effectiveness of CBD for tremor. In addition, research suggests that CBD could be calming for people with Lewy body dementia, a disease related to Parkinson’s. Research shows that people with dementia should avoid marijuana or other products that contain THC.

Side Effects

With the help of the internet, marijuana and Parkinson’s remains a hot topic. In an era where certain self-help books promote marijuana for Parkinson’s, it’s important to keep in mind that cannabis is not a performance-enhancing substance.

Keeping in mind the comedic duo from the 1970s, Cheech and Chong, marijuana makes people move slowly. Other common side effects include:

• Cognitive slowness
• Worsening apathy, lack of motivation
• Memory problems
• Low blood pressure, leading to dizziness and an increased risk of falls
• Increased lung cancer risk or other pulmonary issues from smoking
• Experiencing uneasiness and feeling unwell due to edible cannabis products, which may have less predictable absorption into the body and different dosages

Guidelines for Medical Marijuana and Parkinson’s

Medical marijuana is legal in 29 states, as of early 2018. If you decide to try it for your PD symptoms:

• Inform your doctor. Both you and your doctor should be aware of potential interactions with other drugs, including entacapone (Comtan®) and citalopram (Celexa). Some physicians are not receptive to the use of medical marijuana or are not comfortable filling out state-mandated paperwork. If that’s the case, consider finding a physician who will work with you. Medical marijuana should be approached as a complementary therapy and never a substitute to medication.
• Be aware that cannabis products are not regulated. There is no assurance that one product that says it contains 10 mg of CBD is the same as another.
• Not all marijuana products are the same. Even if two products are the same strain, for example, the cannabinoids in them may be different, and have different effects.
• Stay consistent. To get the most consistent dose, stay with the same product, obtained from the same dispensary or source.
• Start with a low dose. As with all medications, start with a low dose and observe the effects. If you increase the dose, do it gradually.
• Avoid smoking. Oral drops are an alternative.
• Try skin creams or patches for localized pain. Use it like an analgesic cream for certain areas, like the legs.

Conclusion

Cannabis, the marijuana plant, contains more than a hundred different psychoactive chemicals, which have complex effects. Products derived from cannabis may vary widely in terms of their benefits and side effects.

There is currently no conclusive scientific research supporting the benefits of cannabis for any aspect of Parkinson’s. However, anecdotal evidence suggests that cannabis may help pain, sleep, appetite, nausea and anxiety. People with Parkinson’s should especially be aware of side effects such as confusion and low blood pressure that may exacerbate PD symptoms.

For more insights on this topic, listen to our podcast episode “A Western Perspective on PD: Understanding Complementary Medicine”.

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.