Biological sex has a strong influence on the symptoms and course of Parkinson’s disease (PD). Ellen Hess, PhD, of Emory University, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation George G. Kaufman Impact Award to study sex differences in PD.
Previous research has established that males are two times more likely than females to develop Parkinson’s. Men also develop the disease at an earlier age than females and are more likely to have bradykinesia (slowness of movement). In later stages, men have increased daytime sleepiness.
“There are very few studies examining the underlying reasons for sex differences in movement disorders but our knowledge of sex differences in the biology of the central nervous system has grown in leaps and bounds in the past few years,” Dr. Hess said.
Women tend to have more Parkinson’s-related tremors. Women also have greater anxiety and depression, and more severe involuntary movements caused by the Parkinson’s medication levodopa. This is called L-DOPA-induced dyskinesias, or LIDs. Some research suggests estrogen may play a role in delaying or preventing Parkinson’s in women, but estrogen is probably not the only explanation for the differences between males and females.
“The biological reasons for the differences between the sexes are largely unknown and unexplored but nonetheless very important because understanding these differences could ultimately lead to personalized and more effective treatments that are targeted to males or females,” said Dr. Hess.
Dr. Hess’s research will examine sex differences in gene expression in basal ganglia in a mouse model of Parkinson’s and LIDs. The findings could lead to the discovery of drugs specifically targeted to male and female patients using a personalized medicine approach.
“Although I have been working in the role of dopamine in movement disorders for my entire scientific career, much of our work has focused on dystonia, this is actually our first grant on Parkinson’s disease,” said Dr. Hess. “The Parkinson’s Foundation grant is providing my laboratory the opportunity to expand the focus of our work and, for the first time, to contribute to Parkinson’s disease research in a meaningful way.”
Insights Into Brain’s Dopamine System Could Yield New Parkinson’s Treatments
Onur Basak, PhD, of University Medical Center Utrecht - Translational Neuroscience Utrecht, Netherlands, received a Parkinson’s Foundation GeorgeG. KaufmanImpactAward to investigate the role of histones (a type of protein found in chromosomes that bind to DNA) in the development and progression of Parkinson’s disease (PD). This research will yield insights into the dopamine system in the brain that may lead to new treatments for Parkinson’s.
Despite decades of research, we still do not know exactly how Parkinson’s disease develops. A major hallmark of the disease is the loss of brain nerve cells called dopaminergic neurons in two regions of the midbrain. These nerve cells produce the brain chemical dopamine. In people with Parkinson’s, the cells that make dopamine are impaired. Current treatment for loss of motor symptoms focuses on dopamine but cannot offer a cure.
“There is a great need for new therapeutic targets for PD. Our research provides a new perspective that has the potential to implicate new molecular processes that can be ‘hijacked’ for therapeutic approaches in the long run,” said Dr. Basak.
Evidence shows that a biochemical process called methylation of histones is altered in people with Parkinson’s. However, how this happens is not well understood. Dr. Basak will study histone methylation in different types of dopamine-related neurons as well as neighboring cells that are indispensable for their function.
As part of his research, Dr. Basak will look at the way epigenetics — the processes that help direct when individual genes are turned on or off — affect the progression of Parkinson’s. In the long run, this study will contribute to efforts to discover new drug targets for Parkinson’s treatment.
“Investing in fundamental research is the key to finding new venues for treatment, and eventually, a cure for PD,” Dr. Basak said. “Highly ambitious projects can only be carried out with the support of donors supporting this vision, as the Parkinson's Foundation does. This grant will give me the opportunity to turn a highly ambitious aim into reality. Since the grant is prestigious, it will also support my integration in the PD community.”
Tim Sampson, PhD, of Emory University, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to understand how Parkinson’s-linked pesticides affect the gut microbiome, the complex community of bacteria and other microbes in the intestinal tract.
Studies suggest that people with Parkinson’s disease (PD) harbor distinct gut microbiomes. By identifying gut microbiome changes, the effects of those specific changes on the body, and interactions between environmental exposure and genetic factors, Dr. Sampson hopes to link how insecticides trigger these defects of the intestinal tract and trigger Parkinson’s symptoms.
“Going back 200 years to James Parkinson’s first description of the disease, he noted that individuals with the shaking palsy also had dysfunction in their gut,” said Dr. Sampson. “As the field grew to understand the complexity of gut to brain communication and the role of the indigenous microbiome in this communication, it was clear that this path might be involved in neurological diseases, such as PD.”
Exposure to pesticides is a leading environmental risk for many neurological diseases, including Parkinson’s disease. Symptoms in the gut, including constipation and inflammatory bowel disease, often occur before developing Parkinson’s motor symptoms.
The gut microbiome is one of the first parts of the body to interact with oral exposures, for instance, through eating foods with residual pesticides. However, little is known about how the gut and its microbiome respond to insecticides, and how these changes may specifically impact Parkinson’s.”
“We know that PD likely arises from a confluence of genetic and environmental factors,” said Dr. Sampson. “Our study hopes to better understand the etiology of PD by exploring the contributions of the gut microbiome to chemical exposures that trigger PD-like pathology. We hope that this will provide insight at the earliest stages of the disease to better prevent PD and develop new therapeutic targets.”
Exploring Brain Chemicals’ Role in Parkinson’s Cognitive Decline
Scott Owen, PhD, of Stanford University, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study, understand and restore cognitive function in mouse models of Parkinson’s disease (PD). These findings could lead to more effective, targeted treatments for PD.
Many people with Parkinson’s not only experience loss of motor function and slowing of movement, but also experience cognitive changes including impulsive behavior and reduced capacity for flexible learning — the ability to adapt to a changing environment. While pharmacological and surgical treatments can be effective for treating motor symptoms, there is a critical need for better treatments for cognitive symptoms.
“Changes in cognitive function are comparatively poorly understood, but can be life-changing and debilitating,” said Dr. Owen. “By investigating mechanisms underlying these changes using mouse models, and how these mechanisms respond to common treatments including Levodopa and deep brain stimulation, our goal is to build a fundamental understanding of the underlying biology that can be used to modify, develop and innovate future treatments that are tailored to improve cognitive function.”
Research suggests Parkinson’s symptoms arise from an imbalance between two key brain chemicals, dopamine and acetylcholine. Elevated levels of acetylcholine are essential for flexible learning in the healthy brain, but it is not known whether or how disruption of the relationship between dopamine and acetylcholine contributes to the deficits that are observed in Parkinson’s.
Dr. Owen will investigate where and how acetylcholine acts in the brain to facilitate flexible learning, and how this pathway is altered following the loss of dopamine.
“New tools are emerging and driving discovery in neuroscience at an accelerating rate, making this a particularly exciting time to be in the field,” said Dr. Owen. “Multiple innovations are on the horizon targeting all aspects of Parkinson’s disease from diverse standpoints. I am exceptionally enthusiastic about the potential of this work for guiding future treatments of Parkinson’s and gaining a deeper understanding of brain function.”
Of his grant award, Dr. Owen said, “The award from the Parkinson’s Foundation is an absolutely invaluable jump-start for this project. In addition to directly supporting a specific project, this early funding can have a “multiplier” effect by establishing the foundation for a sustained, large-scale effort focused on Parkinson’s research in my lab in the future. Building on the support from the Parkinson’s Foundation, I anticipate that this work will be a core focus of my lab for many years.”
Protecting Midbrain Neurons to Delay or Treat Parkinson’s
Lindsay Mitchell De Biase, PhD, fromthe University of California, Los Angeles, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to gain a better understanding of the role of central nervous system immune cells called microglia in Parkinson’s disease (PD). Ultimately, this work could lead to therapies that delay or treat Parkinson’s.
Microglial cells can shape neuron function and health and remove debris from surrounding tissue. They regulate the signaling connections between neurons (called synapses). They also regulate central nervous system inflammation. Previous research suggests structures within the cell called mitochondria may be able to regulate the function of midbrain microglia and their responses to aging.
“Many gene mutations that increase the risk for Parkinson’s are mutations in genes related to mitochondrial function,” said Dr. De Biase. “We think that some of these mutations are increasing disease risk, not only by affecting energy production within neurons but by pushing microglial into a damaging, inflammatory state.”
Dr. De Biase’s goal is to determine if manipulating the function of microglia can protect midbrain dopamine (DA) neurons, which regulate movement and play an important role in the progression of PD. Currently, there is no way to protect these brain cells.;
“Microglia are dynamic, malleable cells and could represent therapeutic targets that are highly distinct from many that have been explored thus far,” said Dr. De Biase.
Microglia are different in the midbrain compared with other brain regions, Dr. De Biase discovered. During aging, they multiply. They release inflammatory factors earlier than microglia in other brain regions. This creates early “pockets” of inflammation that are likely to interfere with synapse function and neuron health.
These findings suggest that the unique traits of midbrain microglia are key to making DA neurons more vulnerable to Parkinson’s. Discovering what makes these microglia more responsive to aging and disease holds great promise for harnessing these cells to protect DA neurons.
Using new technology, Dr. De Biase will seek to better understand the role of microglial mitochondria in a mouse model of Parkinson’s disease. The intervention strategy she develops could be used in people who are at high risk for developing the disease, to delay or prevent disease onset. In people with PD, it could be used to create a more neuroprotective environment, preserve remaining dopamine neurons, and hopefully, delay disease progression.
Dr. De Biase has taken inspiration in her work from her father, a retired physician, who at times expressed frustration about the limits to what treatments he could offer and was envious of researchers who work to advance scientific knowledge.
“I have always hoped that my research efforts can benefit human health,” Dr. De Biase said. “We clearly need both clinicians and researchers. Even if I can’t meet with patients directly in a consultation room, I am hoping that our research can go on to help numerous people out there who each have their unique stories and struggles with the disease.”
Of the Parkinson’s Foundation grant, Dr. De Biase said, “This award has been absolutely instrumental in giving us the support to pursue these studies. I am a relative newcomer to the field of Parkinson’s research. This award will help us secure additional funding to continue pushing forward in this research direction. Interacting with other researchers and individuals living with PD through the Foundation is also enormously beneficial to our efforts.”
Daniel Silverman, PhD, of the University of California, Berkeley, received a Parkinson’s Foundation James R. "Jim Bob" Moffett, Sr. Postdoctoral Fellowship grant to study the mechanisms that contribute to sleep disturbances in Parkinson’s disease (PD). This could lead to innovative treatments or preventative measures to improve this common side effect of PD.
Sleep can also be negatively impacted by medications that treat other Parkinson’s symptoms, which affect levels of brain chemicals called dopamine and norepinephrine. Brain nerve cells (or neurons) that release these chemicals are also involved in regulating sleep and are among the first neurons to deteriorate in Parkinson’s. The relationship between sleep problems and nerve cell degeneration is not well understood.
Dr. Silverman, who developed novel approaches for revealing the mechanism of retinal degeneration and night blindness from a rhodopsin (light-sensitive receptor protein) mutation in graduate school, was drawn to Parkinson’s research based on the work of Berkeley neuroscientist Yang Dan, PhD.
“After seeing Dr. Dan’s research on sleep, I became curious — often thinking about sleep experiments lying awake at night,” said Dr. Silverman. “It was striking to learn that little is known about the mechanisms that control the brain’s balance between wakefulness and sleep, especially because disruption is a common symptom of Parkinson’s disease.”
Dr. Silverman will focus on the role of molecules called reactive oxygen species (ROS) in PD sleep problems. Emerging evidence has shown that reactive oxygen species build up when neurons release dopamine and norepinephrine. Research also shows these neurons are inhibited by high levels of ROS.
Using a mouse model, Dr. Silverman will try to determine if ROS levels grow during long periods of being awake and whether quality sleep may help cells to recover from the stress caused by ROS. “With a better understanding of the molecular dysregulation that underlies sleep disturbances in Parkinson’s, a targeted treatment could one day aim to restore healthy sleep,” said Dr. Silverman.
Neurons in Basal Ganglia Could Play Key Role in Parkinson’s Motor Symptoms
Connor D. Courtney, PhD of Northwestern University Feinberg School of Medicine (a Parkinson’s Foundation Center of Excellence) received a Parkinson’s Foundation Postdoctoral Fellowship grant to study a part of the brain that plays a key role in Parkinson’s disease (PD) motor symptoms called the external globus pallidus (GPe).
GPe nerve cells, located in a region deep in the brain called the basal ganglia, are key to movement, perception, and judgment.
Dr. Courtney recently discovered that two types of brain nerve cells (neurons) in the GPe serve opposite roles in regulating motor response. He will investigate the role of brain cells called astrocytes in regulating these two cell types. He believes that interactions between GPe neurons and astrocytes may be critically disrupted in PD.
“This award enables me to lay the foundation necessary to unravel the complex roles astrocytes are likely playing in PD,” said Dr. Courtney. “Shockingly little is known about how these intriguing cells contribute to the development of symptomatology of PD, and learning more about them may pave the way for important PD therapies in the future.”
Dr. Courtney attributes his motivation to study Parkinson’s disease to his father, who currently lives with PD. “As an issue with tremendous personal relevance, my overarching aspiration is to take my deep passion for neuroscience and apply it to the study of PD,” said Dr. Courtney. “I am exceedingly grateful to the donors and supporters of the Parkinson’s Foundation! It is an honor to be supported by a foundation that means so much to my family.”
Caution Ahead: Linking Concussions to Parkinson’s and Dementia
A concussion is a type of traumatic brain injury (TBI). They are generally described as self-limiting and on the less-severe end of the brain injury spectrum. It is estimated that as many as 3.8 million concussions occur in the U.S. every year during competitive sports and recreational activities. That number may be even higher ― research shows that upwards of 50 percent of concussions may go unreported. What does a concussion have to do with Parkinson’s disease (PD) and dementia? Possibly a lot.
Recently published in the journal, Family Medicine and Community Health, a study titled “Associations between concussion and risk of diagnosis of psychological and neurological disorders: a retrospective population-based cohort study” (Morissette, Prior, Tate, Wade, & Leiter, 2020), sought to investigate whether having experienced a concussion might increase one’s risk of being diagnosed with PD and dementia, as well as Attention-Deficit Hyperactivity Disorder (ADHD) and Mood and Anxiety disorders (MADs) later in life.
This is not the first study to connect Parkinson’s to concussions. What makes this study different is that it focuses on Parkinson’s and the more common mild concussion (or mild TBI), sustained from falls or exercise-related injuries. Previously, research has focused on studies comparing PD and concussions known as high-impact TBIs ― those related to sports injuries or traumatic contact sustained by the head.
This was a robust, case-controlled, 25-year retrospective study examining medical records from 1990-1991 to 2014-2015. It compared the health outcomes of 47,483 people (28,021 men and 19,462 women) who had suffered concussions with 139,030 (81,871 men and 57,159 women) healthy people (controls) matched by age, sex, socioeconomic status and geographical location. The study used several statistics models among other sensitivity models.
Results
Regardless of age, sex, socioeconomic status and residence, having suffered a single concussion in one’s lifetime increased the likelihood of later being diagnosed with:
Parkinson’s disease by 57%
Dementia by 72%
ADHD (Attention-Deficit Hyperactivity Disorder) by 39%
Mood and Anxiety Disorders (MADs) by 72%
Sustaining multiple concussions further increased the risk for developing both PD and dementia.
What Does It Mean?
While the CDC considers most TBIs reported annually to be mild, this study found that experiencing a concussion may, in fact, be a substantial risk factor for developing Parkinson’s disease and dementia (as well as ADHD and MADs).
Having a single concussion increased the risk of developing PD by 57% and dementia by 72%; and having multiple concussions further increased the risk of developing PD and dementia compared to people who suffered only one concussion. While additional studies are surely warranted, this study suggests that concussions should be taken more seriously by healthcare providers, as there may be unanticipated, long-term neurological effects.
Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the association of brain injuries and PD by visiting the below Parkinson’s Foundation resources, or by calling our free Helpline at 1-800-4PD-INFO (473-4636) for answers to all your Parkinson’s questions.
Dewan, M. C., Rattani, A., Gupta, S., Baticulon, R. E., Hung, Y. C., Punchak, M., . . . Park, K. B. (2018). Estimating the global incidence of traumatic brain injury. J Neurosurg, 1-18. doi:10.3171/2017.10.JNS17352
Harmon, K. G., Drezner, J. A., Gammons, M., Guskiewicz, K. M., Halstead, M., Herring, S. A., . . . Roberts, W. O. (2013). American Medical Society for Sports Medicine position statement: concussion in sport. Br J Sports Med, 47(1), 15-26. doi:10.1136/bjsports-2012-091941
Ilie, G., Boak, A., Adlaf, E. M., Asbridge, M., & Cusimano, M. D. (2013). Prevalence and correlates of traumatic brain injuries among adolescents. JAMA, 309(24), 2550-2552. doi:10.1001/jama.2013.6750
McKee, A. C., & Daneshvar, D. H. (2015). The neuropathology of traumatic brain injury. Handb Clin Neurol, 127, 45-66. doi:10.1016/B978-0-444-52892-6.00004-0
Morissette, M. P., Prior, H. J., Tate, R. B., Wade, J., & Leiter, J. R. S. (2020). Associations between concussion and risk of diagnosis of psychological and neurological disorders: a retrospective population-based cohort study. Fam Med Community Health, 8(3). doi:10.1136/fmch-2020-000390
Joe Dunn, newly named Reach Further campaign co-chair for the Parkinson’s Foundation Heartland chapter, attributes his desire to support Parkinson’s disease (PD) research to his late grandmother’s 10-year battle with the disease.
Further inspired by the ambitious goals set forth in the Reach Further campaign, which include raising an additional $30 million to advance research and expand care and community programs, Joe and the Dunn Family also pledged a leadership campaign gift of $250,000.
The campaign’s emphasis on expanding PD GENEration: Mapping the Future of Parkinson’s disease, which will provide up to 15,000 people with PD no-cost genetic testing and counseling, is particularly impactful for Joe and his family.
“This campaign, and its focus on genetic research, is really important to the family because we are at risk later in life,” said Joe. “The reason I stepped up is because this focus on identifying the genetic factors of PD is something I think lots of people will want to get behind and donate towards, and I want to be part of that."
As Reach Further regional co-chair, Joe will lead campaign fundraising efforts within the Parkinson’s Foundation Heartland Chapter and will work to inspire others to support the campaign’s critical goals.
Joe, who lives in the Kansas City area, close to top medical providers, is passionate about the Reach Further campaign’s focus on expanding quality neurocognitive care into the rural regions that the Heartland chapter encompasses.
“Across the country, access to specialized care in rural areas is a huge issue. My grandmother had a top movement disorder specialist who is director of the Parkinson’s Foundation Center of Excellence at the University of Kansas Medical Center. Many others don’t have access to such high-quality medical attention but lots of people with PD would like access to that level of care.”
For Joe, the Foundation’s three-priority approach to research, care and community support also matters tremendously. “The thing that sets the Parkinson’s Foundation apart is the community outreach and education pieces,” said Joe. “Ultimately, you need a holistic approach to deal with a complex disease like PD.”
Joe recalled that prior to his grandmother’s passing in 2013, there was much uncertainty around her diagnosis, as well as a hesitance to share her struggles with her family. “For the longest time, no one knew what she had,” Joe said. “She was hunched over for the last five years of her life, but did not talk openly about it. She was embarrassed that she needed help. This is why I feel so strongly about creating awareness and acceptance around PD, in her memory.”
Joe offered the following advice to other families who are dealing with Parkinson’s: “The biggest thing is to be supportive and be patient. A lot of people don’t want others to know what’s going on, but be supportive anyway you can, and be proactive about reaching out for resources and help. The Parkinson’s Foundation is a great place to start.”
Watch our live Q&A with our National Medical Director, Dr. Michael S. Okun, about coronavirus, Parkinson's disease and hospitalization.
Watch our live Q&A with our National Medical Director, Dr. Michael S. Okun, about coronavirus and Parkinson's disease.
Watch our special Facebook Live event below with our National Medical Director, Dr. Michael S. Okun, and infectious disease expert, Dr. Frederick S. Southwick, both of the University of Florida. This video was filmed March 18, 2020. For up-to-date information on coronavirus, read our latest blog post, "Looking Ahead: Parkinson's, COVID-19 & the New Normal."
Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person, according to the Centers for Disease Control. Seniors are the most vulnerable. Since most people with Parkinson’s disease (PD) are in their senior years, the Parkinson’s Foundation wants you to be prepared for COVID-19 and Parkinson’s.
About the Coronavirus (COVID-19)
Coronaviruses are a family of viruses that are like the common cold, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). In 2019, a new virus formed and spread from China to other countries, including the U.S. now called coronavirus disease 2019 or COVID-19.
Signs and symptoms of infection with COVID-19 may appear two to 14 days after exposure and can include fever, cough, shortness of breath or difficulty breathing. There is currently no cure or vaccine, however researchers are working on creating a vaccine. Those who believe they may have the illness should call their doctor immediately for next steps. Read the Centers for Disease Control (CDC) factsheet here.
Seniors and Coronavirus
Seniors are most at risk to develop COVID-19 and its symptoms, which can lead to the development of pneumonia. Seniors should strongly consider getting the pneumonia vaccine as soon as possible or speaking about it with their doctor.
In general, viruses spread faster in residential facilities, community housing and assisted living centers. When possible, seniors living in these facilities should avoid communal rooms and sanitize often.
Preparedness for People with Parkinson’s
People with Parkinson’s and care partners should take these tips into consideration to be better prepared for COVID-19:
Everyday Precautions
Wash your hands. Wash them often with soap and water for at least 20 seconds.
Carry hand sanitizer. When in public spaces use an alcohol-based hand sanitizer that contains at least 60% alcohol.
Sanitize around you. Stay as healthy as possible and use disinfectant wipes in public areas.
Know the symptoms. Primary symptoms include mild to severe respiratory illness with fever, cough and/or shortness of breath.
Avoid touching your eyes, nose and mouth with unwashed hands.
Stock up on essential supplies. Consider grocery delivery or asking a family member or friend to help with groceries.
Practice social distancing as an everyday precaution. Stay six feet, or more, away from others.
Limit outings. If you must go out in public for essentials, practice social distancing, avoid crowded areas, wear a cloth face covering and wash your hands often.
During a COVID-19 outbreak in your community, stay home as much as possible to reduce your risk of being exposed.
Avoid air travel and all non-essential travel.
PD Preparedness
Check all your medications. Take inventory of all medications and reorder any that are running low.
Write your medication list down. Write down or print a list of all your medications (not just PD medications). Include medication name, strength, times taken and dosages. This customizable medication schedule can help.
Make a list of your doctors. Make a list of your doctors and their contact information and take it with you in the event of a hospitalization.
Stock your Aware in Care kit in the event you need to educate a health care professional about your PD needs. Order one here.
PD Hospitalization and Coronavirus Preparedness Fact Sheet:Download this document that has crucial information for healthcare professionals in the case you are hospitalized during the COVID-19 outbreak.
Know your community response plan. Check in with your state’s emergency management agency here.
The Parkinson's Foundation will continue to monitor and report on COVID-19 at Parkinson.org/Coronavirus.
In-Person Events
After careful consideration, the majority of Parkinson's Foundation events are now virtual.
Even though all Moving Day events have been postponed, stay tuned for more information about Moving Day. Attend virtually to help us raise Parkinson’s awareness and funds to make life better for people with Parkinson’s. Learn more.
Virtual Events
Virtual events will continue as scheduled. Please check Parkinson.org/Events for all upcoming events.
If you have questions about Parkinson's disease call our free Helpline at 1-800-4PD-INFO (473-4636) or email Helpline@Parkinson.org to contact an information specialist.
