The research is published in the January 26, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study looked at several types of flavonoids and found that higher consumption of flavan-3-ols and anthocyanins, both before and after a Parkinson’s diagnosis, was associated with lower risk of death during the study period.

Flavonoids are naturally occurring compounds found in plants and are considered powerful antioxidants. Previous research has shown that flavonoids may have a protective effect on the brain.

“Our results are exciting because they suggest that people with Parkinson’s in our study who did something as simple as including three or more servings per week of common foods like red berries, apples and orange juice may have improved chances of living longer,” said study author Xiang Gao, M.D., Ph.D,, of The Pennsylvania State University in University Park.

The study looked at 1,251 people with Parkinson’s with an average age of about 72. Researchers used a food frequency questionnaire to determine people’s flavonoid intake before and after their diagnosis, for an average of 33 years. Every four years, people were surveyed about how often they ate various foods, including tea, apples, berries, oranges and orange juice. Their intake of different types of flavonoids was calculated by multiplying the flavonoid content of each food by its frequency.

By the end of the study, 944, or 75%, of the participants had died. Of those, 513 people died from Parkinson’s, 112 died from cardiovascular diseases and 69 died from various cancers.

The people in the group that represented the highest 25% of flavonoid consumers, on average, had about 673 milligrams (mg) in their diets each day, compared to the people in the lowest 25% of flavonoid consumers, who had about 134 mg in their diets each day. Strawberries, for example, have about 180 mg of flavonoids per 100 gram serving, while apples have about 113.

After adjusting for factors like age and total calories, the group of highest flavonoid consumers had a 70% greater chance of survival compared to people in the lowest group.

Gao notes that higher consumption of flavonoids before a person’s Parkinson’s diagnosis was associated with a lower risk of dying from any cause in men, but not in women. After diagnosis, of the 163 men in the top group of consumers, 120 died during the study, compared to 129 of the 163 men in the bottom group. Among women, 96 of the 150 in the top group died, compared to 96 of the 149 in the bottom group. However, researchers found that after a person’s diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

Researchers also looked at individual flavonoids. For example, the people in the group representing the top 25% consumers of anthocyanins, found in red wine and berries, had an average 66% greater survival rate compared to those who represented the lowest consumers of that particular flavonoid. For flavan-3-ols, found in apples, tea and wine, the top 25% of consumers, on average, had a 69% greater survival rate compared to the lowest 25% of consumers.

The study does not prove that people with Parkinson’s who eat a diet rich in flavonoids will have a better survival rate. It shows an association.

“More research is needed to understand why people with Parkinson’s who have diets higher in flavonoids may have better survival rates,” Gao said. “However, if someone with Parkinson’s is able to add a few servings of berries, apples, oranges and tea to their weekly diets, our results suggest it may be an easy and low-risk way to possibly improve their outcome. And while we do not encourage people who do not currently drink alcohol to start, people who do drink could consider shifting to red wine.”

A limitation of the study is that results were not adjusted to consider the severity of a person’s Parkinson’s disease at the beginning of the study.

The study was supported by the National Institute of Neurological Disorders and Stroke.

Learn more about Parkinson’s at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

The study also found that how well different compensation strategies worked depended on the context in which they were used, such as indoors versus outdoors, under time pressure or not.

“We know people with Parkinson’s often spontaneously invent creative ‘detours’ to overcome their walking difficulties, in order to remain mobile and independent,” said study author Anouk Tosserams, MD, of the Radboud University Medical Centre in Nijmegen, the Netherlands. “For example, people walk to the rhythm of a metronome, by mimicking the gait of another person, or by counting in their head. We found that people are rarely educated about all the different compensation strategies. When they are, people often find strategies that work better for them and their unique circumstances.”

For the study, researchers surveyed 4,324 people with Parkinson’s and disabling gait impairments. These include problems like imbalance, shuffling, falling, staggering and freezing. Of the participants, 35% found that their walking difficulties affected their ability to perform their usual daily activities and 52% had one or more falls in the past year.

The survey explained the seven main categories of compensation strategies. They are: internal cueing, like walking to a count in your head; external cueing, like walking in rhythm to a metronome; changing the balance requirement, like making wider turns; altering mental state, which includes relaxation techniques; action observation and motor imagery, which includes watching another person walk; adapting a new walking pattern, like jumping or walking backwards; and other forms of using the legs, like bicycling and crawling. Each category was explained and participants were asked if they were aware of it, if they’d ever used it, and if so, how it worked for them in a variety of contexts.

Researchers found that people with Parkinson’s commonly use walking compensation strategies, but are not aware of all seven strategies. For example, 17% of the people had never heard of any of these strategies, and 23% had never tried any of them. Only 4% were aware of all seven categories of compensation strategies. The average person knew about three strategies. Other than the use of walking aids and alternatives to walking, the best-known strategy was external cueing, like listening to a metronome, known by 47% of the respondents. That was followed by internal cueing, known by 45%. Action observation and motor imagery was the least known category, known by 14%.

For each strategy, the majority of people who tried it said it had a positive effect. For example, 76% said changing the balance requirement made a positive impact, while 74% said altering their mental state did.

However, researchers also discovered that strategies worked differently according to the context in which the person used it. Internal cueing, for example, seemed highly effective during gait initiation, with a 73% success rate. Only 47% found that tactic useful when trying to stop walking. Similarly, visualizing the movements had an 83% success rate when people used it walking outdoors. It only had a 55% success rate when people used it to navigate a narrow space.

“Our findings suggest that a ‘one-size-fits-all’ approach doesn’t work, because different contexts might require different strategies, or because individuals simply respond better to one strategy compared to another,” Tosserams said. “We need to go a step further and teach people about all the available compensation strategies, for example through a dedicated online educational platform. This may help each person with Parkinson’s find the strategy that works best for them.”

A limitation of the study is that people reported their own gait disability, which was not confirmed by an independent neurological examination.

The study was supported by the Netherlands Organization for Health and Research Development.

Learn more about Parkinson’s at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

The results, from a pilot study by Iowa State researchers, showed improvements in patients’ mood and motor symptoms, as well as reduced physiological indicators of stress. Elizabeth Stegemöller, an assistant professor of kinesiology, cautioned that the data is preliminary, but says the improvements among singing participants are similar to benefits of taking medication. Stegemöller presented the work at the Society for Neuroscience 2018 conference.

Parkinson’s is a progressive nervous system disorder characterized by muscle tremors, which often start in the hand, and stiffness in movement.

“We see the improvement every week when they leave singing group. It’s almost like they have a little pep in their step. We know they’re feeling better and their mood is elevated,” Stegemöller said. “Some of the symptoms that are improving, such as finger tapping and the gait, don’t always readily respond to medication, but with singing they’re improving.”

Stegemöller, Elizabeth “Birdie” Shirtcliff, an associate professor in human development family studies; and Andrew Zaman, a graduate student in kinesiology, measured heart rate, blood pressure and cortisol (the so-called “stress hormone”) levels for 17 participants in a therapeutic singing group. Participants also reported feelings of sadness, anxiety, happiness and anger. Data was collected prior to and following a one-hour singing session.

This is one of the first studies to look at how singing affects heart rate, blood pressure and cortisol in people with Parkinson’s disease. All three levels were reduced, a positive development, but Stegemöller says with the preliminary data the measures weren’t statistically significant. There were no significant differences in happiness or anger after class. However, participants were less anxious and sad.

Despite the encouraging results, researchers still have to solve the puzzle of what mechanism leads to these changes.

They are now analyzing blood samples to measure levels of oxytocin (a hormone related to bonding), changes in inflammation (an indicator of the progression of the disease) and neuroplasticity (the ability of the brain to compensate for injury or disease) to determine if these factors can explain the benefits of singing.

“Part of the reason cortisol is going down could be because the singing participants feel positive and less stress in the act of singing with others in the group. This suggests we can look at the bonding hormone, oxytocin,” Shirtcliff said. “We’re also looking at heart rate and heart rate variability, which can tell us how calm and physiologically relaxed the individual is after singing.”

The research builds upon the team’s previous findings that singing is an effective treatment to improve Parkinson’s patients’ respiratory control and the muscles used for swallowing. The prevalence of Parkinson’s disease is expected to double over the next 20 years. ISU researchers say therapeutic singing has the potential to provide an accessible and affordable treatment option to improve motor symptoms, stress and quality of life for Parkinson’s patients.

As a result, the pool of candidates for clinical trials is dramatically reduced, says the paper, published in npj Parkinson’s Disease.

Parkinson’s disease (PD) is a disorder of the central nervous system that affects movement. Symptoms include tremors, stiffness, and slow and small movement. The pace of progression varies among patients, making the months following diagnosis crucial to researchers studying the disease’s progression.

“The critical time of about one year from when the patient can be diagnosed with early PD based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” said lead author Robert A. Hauser, MD, director of the Parkinson’s & Movement Disorder Center at the University of South Florida. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”

Hauser says that in order to determine whether a potential disease-slowing therapy is actually working, researchers must be able to compare the therapy to a placebo without interference from symptomatic treatment. Otherwise, they won’t know if the therapy is slowing the disease’s progression or if they are just seeing the effects of symptomatic treatment.

This requires patients to seek assessment soon after they notice the onset of tremor or slow movement. In addition, physicians should consider referring patients to clinical trials soon after diagnosis and delaying the prescription of symptomatic medicine until it’s necessary. If a patient waits until symptomatic treatment is necessary, the opportunity to participate in these crucial clinical trials is lost.

Understand Your Diagnosis.

Take a deep breath and ask what stage you are and what symptoms he used to make the diagnosis. Based on your condition, determine which medications are recommended and their side effects. Ask about alternative natural treatments for Parkinson’s (versus traditional medicine) and their availability. Ask what type of lifestyle changes slow down Parkinson’s, such as level of fitness, the role of exercise, and what types.

Form a Team.

You cannot do it alone.  From physicians to family, it takes teamwork and specialists to put Parkinson’s on the defense.

Know Your Medications.

There are two basic categories of Parkinson’s medications Dopamine Agonist and Carbidopa Levodopa.  Over time, the type and dosage of your Parkinson’s medications will change as effectiveness evolves. Pay special attention to any compulsive behavior changes that arise from how the medication is interacting your basic physical and mental make-up.

Work on Postural Alignment.

Better known as posture, this can be improved by sitting up straight, shoulders back, chest out and head back.  Remind yourself every day to be conscious of your posture and over time you will see a difference. Standing tall with your shoulders back presents the image that you are Parkinson’s-free. People will notice your improved posture and it will have a positive impact in improving your attitude.

Follow a Fitness Plan.

The goal of a fitness plan is to have a body that is lean, flexible and strong. The ideal fitness plan encompasses a variety of exercises for the entire body. Going to the gym five days a week for two hours will enable you reach an ideal level of fitness.

Make for a Safe Home.

The first priority is to make your home safe to move around in by keeping walkways clear of obstructions, as well as removing rugs or other floor obstacles that are tripping hazards. Install grab bars and railings where there are critical areas of movement or changes in direction.

Pay Attention to Nutrition.

A balanced diet is important to provide your body with the fuel for maintaining the strength necessary to deal with Parkinson’s. Ideally, meals should be spread out throughout the day to provide a steady flow of nutrients to fuel the body. Snacks of nuts, fruits and berries provide a boost during the day. Reducing alcohol consumption, sugar and fried foods will also be a benefit to improving your health.

Get a Good Night’s Sleep.

Nighttime sleep is critical for the body to restore and rejuvenate the energy needed for the continual fight with Parkinson’s. Unbroken sleep for 7–8 hours is a necessity and does not include daytime naps.

Master the Mental and Emotional Game.

The hardest part of Parkinson’s is dealing with depression, stress and anxiety. We are constantly barraged with negativity throughout the day, from the Parkinson’s itself to the news to diminishing physical and cognitive influences. One way to combat this awful trait of Parkinson’s is through positive psychology and incorporating happiness on a daily basis.

Stay Committed.

Improving your health and daily life requires an unwavering commitment to the principles and tenets of The Parkinson’s Playbook. The most important factor in putting Parkinson’s on the defense is to make a commitment to fitness and exercise on a daily basis. It will fuel your happiness and lead to a fuller life.

 
Robert W. Smith is a Parkinson’s disease advocate. His own diagnosis with Parkinson’s disease has inspired him to be a mentor to those suffering from the same debilitating condition. He is the author of an enlightening and engaging book, The Parkinson’s Playbook: A Game Plan to Put Your Parkinson’s on the Defense. Professionally, Robert has enjoyed a successful career as a landscape architect, and is a Fellow in the American Society of Landscape Architects. He currently lives in Denver, CO.

 MIND AND BODY PRACTICES

TAI CHI

There is some evidence that tai chi, along with medication, may improve some symptoms of Parkinson’s disease, such as balance and functional mobility.

The Evidence Base

The evidence base on efficacy of tai chi for symptoms of Parkinson’s disease consists of several randomized controlled trials and systematic reviews and meta-analyses.

Efficacy

A 2015 systematic review and meta-analysis of 15 randomized controlled trials involving 799 participants found positive evidence of tai chi plus medication for Parkinson’s disease for improvements in motor function, balance, and functional reach; however, no significant difference was found between tai chi plus medication and medication alone for gait or quality of life.

A 2015 systematic review of 64 studies of nonpharmacologic [non-drug] approaches to improve balance in Parkinson’s disease found some evidence that tai chi may help improve balance and motor control abilities; however, a 2013 randomized controlled trial showed that 16 weeks of tai chi training were ineffective in gait performance, gait initiation, or the reduction of disability related to Parkinson’s disease.

A 2014 systematic review and meta-analysis of seven randomized controlled trials and one non-randomized controlled trial involving a total of 470 participants found that tai chi showed beneficial effects in improving motor function, balance, and functional mobility in participants with Parkinson’s disease, but not in improving gait velocity, step length, or gait endurance. However, when compared to other active therapies, tai chi only showed better effects in improving balance.

A 2014 systematic review and meta-analysis of 10 randomized controlled trials involving a total of 409 participants with mild-to-moderate Parkinson’s disease concluded that tai chi, performed with medication, resulted in improvements in mobility and balance.

Safety

Tai chi is generally considered safe for most people. A 2014 systematic review and meta-analysis of 10 randomized controlled trials concluded that tai chi was safe and popular among participants with Parkinson’s disease who are at an early stage of disease.

ACUPUNCTURE

Clinical studies in China have shown a positive benefit of acupuncture in treating symptoms of Parkinson’s disease; however, large and well-controlled clinical trials are needed before a conclusion about the efficacy of acupuncture for this condition can be drawn. The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute the use of acupuncture in Parkinson’s disease.

The Evidence Base

The evidence base on efficacy of acupuncture on symptoms of Parkinson’s disease consists of a couple of reviews of only a few clinical trials of poor methodological quality.

Efficacy

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute the use of acupuncture in Parkinson’s disease.

A 2015 systematic review and meta-analysis of 27 studies involving 2,314 participants evaluating the effectiveness of traditional Chinese medicine as an adjunct therapy for Parkinson’s disease found that acupuncture (based on two studies of 98 participants) as adjunct therapy was markedly beneficial for improving some Parkinson’s-related symptoms compared to routine treatment alone.

A 2014 review of 11 studies concluded that the lack of randomized controlled trials and small sample size were not sufficient to demonstrate favorable effects of acupuncture on Parkinson’s disease.

Safety

Acupuncture is generally safe and well-tolerated in most people when it is performed by a licensed practitioner.

MASSAGE THERAPY

There is insufficient evidence to determine whether massage therapy has any beneficial effect on symptoms of Parkinson’s disease.

The Evidence Base

The evidence base on efficacy of massage therapy for symptoms of Parkinson’s disease consists of only a few small clinical trials.

Efficacy

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute manual therapy, including massage therapy, biofeedback, or Alexander technique in the treatment of Parkinson’s disease.

A 2013 randomized controlled pilot study of 45 participants with Parkinson’s disease found that salivary cortisol (a natural biomarker for stress) concentrations were significantly reduced immediately following the tactile massage intervention, but there were no significant differences in reduction compared to the control group and no long-term effect.

Safety

Massage therapy is generally safe and well-tolerated in most people when it is performed by a licensed practitioner.

DANCE

There is some limited evidence that dance, such as the Argentine tango, can be a supportive approach for people with Parkinson’s disease and has the potential to improve specific symptoms of Parkinson’s, including motor severity and balance over the short term.

The Evidence Base

The evidence base on efficacy of dance interventions for symptoms of Parkinson’s disease consists of several randomized controlled trials and a few systematic reviews and meta-analyses. Most studies have been small and have been less rigorous in design.

Efficacy

A 2015 systematic review and meta-analysis of 13 studies evaluated research results on the effectiveness of Argentine tango for people with Parkinson’s disease and found significant overall effects in favor of tango for motor severity and balance. However, the studies were small and many were conducted by the same research groups.

A 2013 clinical trial involving 31 participants examined the effects of adapted tango on spatial cognition and disease severity in Parkinson’s disease and found that the tango participants improved on disease severity and spatial cognition, compared with the control group. Improvements among the tango participants were also seen in balance and executive function.

A 2013 randomized controlled trial of 52 participants with Parkinson’s disease found that those who participated in a community-based Argentine tango class reported increased participation in complex daily activities, recovery of activities lost since the onset of Parkinson’s disease, and engagement in new activities.

When comparing the differential effects of tango versus other types of dance for Parkinson’s disease, a 2015 study of 11 participants concluded that tango dance interventions may preferentially improve mobility and motor signs in people with Parkinson’s disease, compared to other dance interventions.

A 2015 randomized controlled trial of 20 participants examined the effects of virtual reality dance exercise on people with Parkinson’s disease and found that virtual reality dance exercise had a positive effect on balance, activities of daily living, and depressive disorder status.

A 2014 systematic review and meta-analysis of five randomized controlled trials found that dance as an intervention for Parkinson’s disease significantly improved motor scores, balance, and gait speed when compared to no treatment. When compared with other exercise interventions, significant improvements in balance and quality of life were found.

Safety

Dance interventions in people with Parkinson’s disease are generally considered safe when practiced in a controlled environment. Dancing with a partner may provide an added safety element in preventing falls by holding on to the partner.

NATURAL PRODUCTS

 COENZYME Q10

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute the use of coenzyme Q10 for neuroprotection.

The Evidence Base

The evidence base on efficacy of coenzyme Q10 for Parkinson’s disease consists of a few clinical trials.

Efficacy

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute the use of coenzyme Q10 for neuroprotection.

A 2014 randomized clinical trial of 600 participants with Parkinson’s disease concluded that coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.

A 2002 randomized controlled trial of 80 participants with early Parkinson’s disease found that less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo; however, the results did not reach statistical significance.

Safety

Studies have not reported serious side effects related to CoQ10 use. The most common side effects of CoQ10 include insomnia, increased liver enzymes, rashes, nausea, upper abdominal pain, dizziness, sensitivity to light, irritability, headaches, heartburn, and fatigue.

CoQ10 may make warfarin less effective.

CREATINE

There is insufficient evidence to determine whether creatine used alone or as an adjuvant treatment is efficacious for Parkinson’s disease.

The Evidence Base

The evidence base on the efficacy of creatine for Parkinson’s disease consists of only a few small randomized controlled trials and a systematic review.

Efficacy

A 2014 systematic review of two randomized controlled trials involving 194 participants concluded that the evidence base on the effects of creatine in Parkinson’s disease is limited by risk of bias, small sample sizes, and short duration of clinical trials, and does not provide a reliable basis on which treatment decisions can be made.

Safety

The systematic review found that creatine appears to be safe and well-tolerated; however, there was a higher rate of patients with gastrointestinal complaints in the creatine group compared to the placebo group at 2 years followup.

MUCUNA PRURIENS (VELVET BEAN)

There is insufficient evidence to support or refute the use of Mucuna pruriens for the treatment of Parkinson’s disease symptoms.

The Evidence Base

The evidence base on efficacy of Mucuna pruriens on symptoms of Parkinson’s disease consists of only one preliminary pilot study

Efficacy

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that there is insufficient evidence to support or refute the use of Mucuna pruriens for the treatment of motor symptoms of Parkinson’s disease.

A 2004 preliminary pilot study of eight participants with Parkinson’s disease found that the seed powder formulation of Mucuna pruriens contains a considerable quantity of L-dopa and has a rapid onset of action with a slightly longer duration of therapeutic response compared with standard L-dopa. Mucuna pruriens’s long-term efficacy and safety has not yet been established.

Safety

The safety of Mucuna pruriens has not yet been established.

VITAMIN E

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that Vitamin E is probably ineffective for the treatment of Parkinson’s disease.

The Evidence Base

The evidence base on efficacy of vitamin E for the treatment of Parkinson’s disease consists of only a few clinical trials.

Efficacy

The American Academy of Neurology’s practice parameter on neuroprotective strategies and alternative therapies for Parkinson’s disease concluded that vitamin E is probably ineffective for the treatment of Parkinson’s disease and recommended that for patients with Parkinson’s disease, vitamin E should not be considered for symptomatic treatment.

A large 1993 clinical trial involving 800 participants with early stage Parkinson’s disease evaluated the effects of deprenyl (a monoamine oxidase inhibitor) and tocopherol (a component of vitamin E) on the progression of disability and found that tocopherol did not delay the onset of disability associated with Parkinson’s.

Safety

High doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation.

Results from a large SELECT trial show that vitamin E supplements (400 IU/day) may harm adult men in the general population by increasing their risk of prostate cancer. Followup studies are assessing whether the cancer risk was associated with baseline blood levels of vitamin E and selenium prior to supplementation as well as whether changes in one or more genes might increase a man’s risk of developing prostate cancer while taking vitamin E.

For more information from the NCCIH on complementary and integrative health, click here.

The researchers, from the University of Alabama at Birmingham, has shown that the most common genetic cause of Parkinson’s disease — a mutant LRRK2 kinase enzyme — contributes to the formation of inclusions in neurons, resembling one of the hallmark pathologies seen in Parkinson’s disease. These inclusions are made up of aggregated alpha synuclein protein, which — the research also shows — can be prevented from forming by using two LRRK2 kinase inhibitor drugs now being developed for clinical use.

The interaction between mutant LRRK2 kinase and alpha-synuclein “may uncover new mechanisms and targets for neuroprotection,” the researchers write in a recent Journal of Neuroscience paper. “These results demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of Parkinson’s disease-associated pathology.”

The potential clinical applications for novel neuroprotection strategies in LRRK2-linked Parkinson’s need to be tested in other preclinical models of Parkinson’s disease, say the researchers, led by corresponding author Laura A. Volpicelli-Daley, Ph.D., and senior author Andrew B. West, Ph.D., Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology.

“These data give us hope for the clinical potential of LRRK2 kinase inhibitors as effective therapies for Parkinson’s disease,” Volpicelli-Daley said. “The LRRK2 kinase inhibitors may inhibit the spread of pathologic alpha-synuclein, not only in patients with LRRK2 mutations, but in all Parkinson’s disease patients. Future studies to validate the safety and efficacy of the LRRK2 inhibitors will be necessary before testing the inhibitors in human clinical trials.”

Besides Parkinson’s disease, alpha-synuclein also plays a central role in development of dementia with Lewy bodies and multiple system atrophy, and it is associated with Alzheimer’s disease and other neurodegenerative disorders.

Using a new method for manipulating neurons in a mouse model of Parkinson’s, a Columbia University Medical Center (CUMC) research team found that dyskinesia arises when striatonigral neurons become less responsive to the inhibitory neurotransmitter GABA. This suggests that it may be possible to modify the activity of these neurons to prevent or delay this disabling side effect.

The paper was published in the journal Neuron.

Parkinson’s, a progressive neurodegenerative disorder, results from the death of cells in various parts of the brain, especially in a region called the substantia nigra. It is in the substantia nigra that a neurotransmitter called dopamine is formed, and when dopamine is lacking, neurons fire abnormally, impairing one’s ability to control movement.

“While Parkinson’s is not curable, it is treatable with L-DOPA, which is converted into dopamine in the brain,” said study leader David L. Sulzer, PhD, a professor of neurobiology in the Departments of Neurology, Psychiatry, and Pharmacology at CUMC and a research scientist at the New York State Psychiatric Institute. “However, while taking L-DOPA helps patients move normally, in many individuals it eventually triggers uncontrolled excessive movements.” Parkinson’s is estimated to affect about one million people in the U.S. and up to 10 million worldwide.

According to a news release from Columbia, most studies into the cause of dyskinesia in Parkinson’s have focused on the dopamine receptors that remain in the brain, which over time become over-reactive to L-DOPA therapy. However, the CUMC team decided to look at how neurons of the basal ganglia regulate movement in the absence of dopamine.

“Dopamine neurons modulate the basal ganglia,” explained lead author Anders Borgkvist, PhD, a postdoctoral fellow in Dr. Sulzer’s laboratory. “And because that circuit is still running in patients with Parkinson’s, it’s long been suspected that other parts of the circuit behave abnormally in this disease.”

The CUMC team employed a novel form of optogenetics, a technique that uses light to control neurons that have been genetically sensitized to light, and found that after long-term dopamine loss, striatonigral neurons lose their ability to respond to the neurotransmitter GABA (gamma-aminobutyric acid). This effect was not found with short-term dopamine loss.

“Our findings suggest that GABA and GABA receptors are still present in the striatonigral neurons,” said Dr. Borgkvist. “So then the question becomes, why they aren’t functional? I think that we, or another lab, will eventually find the answer. In any case, the implication is that this defect is correctable, and that would mean that we could prevent or at least delay dyskinesia, so that patients could continue to use L-DOPA.”

A release from McGill explains that the study looked at whether a social and physical activity linked to music, such as tango, could have possible therapeutic value for PD patients who characteristically suffer from motor dysfunctions—tremor, rigidity, gait dysfunction—as well as from non-motor symptoms, such as depression, fatigue and cognitive degeneration. Forty men and women with idiopathic Parkinson’s disease participated in the study, which involved studio classes with two professional dance teachers. Patients were from the Movement Disorders Clinics of the McGill University Health Centre.

The release quotes says Dr. Silvia Rios Romenets, lead researcher in the study with a special interest in Parkinson’s disease and dance therapy, as saying, “There’s accumulating evidence that habitual physical activity is associated with a lower risk of developing PD, which suggests a potential slowing of PD progression. In the study, we found the tango was helpful in significantly improving balance and functional mobility, and seemed to encourage patients to appreciate their general course of therapy. We also found modest benefits in terms of patients’ cognitive functions and in reducing fatigue. No significant changes were detected in overall motor functions.” Dr. Rios Romenets is a clinical research fellow at the Movement Disorders Clinics at The Neuro and Montreal General Hospital.

Argentine tango may be particularly helpful for improving balance and functional mobility in patients with PD. Tango requires specific steps that involve rhythmically walking forward and backward. This may be particularly helpful for walking difficulties especially for freezing of gait and to prevent backward falls. In addition, tango requires working memory, control of attention, and multitasking to incorporate newly learned and previously learned dance elements, to stay in rhythm with the music, and maneuver around others on the dance floor.

Many PD patients find traditional exercise programs unappealing. Over half of PD patients fail to get their recommended daily dose of physical activity. There is however, a connection between music and the dopamine systems in the brain – which are pivotal for establishing and maintaining behavior. So, combining music with exercise in dance such as the tango, can increase accessibility, enjoyability, and motivation, as well as improving mood and stimulating cognition. Also, the social interaction and social support involved in tango have positive results on mood and compliance.

A release from the American Academy of Neurology quotes study author Ildefonso Rodriguez-Leyva, MD, at Central Hospital at the University of San Luis Potosi in San Luis Potosi, Mexico as saying, “Until now, pathological confirmation was not possible without a brain biopsy, so these diseases often go unrecognized until after the disease has progressed. We hypothesized that since skin has the same origin as brain tissue while in the embryo that they might also show the same abnormal proteins. This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.”

The release explains that for the study, researchers took skin biopsies from 20 people with Alzheimer’s disease, 16 with Parkinson’s disease, and 17 with dementia caused by other conditions and compared them to 12 healthy people in the same age group. They tested these skin samples to see if specific types of altered proteins were found–ones that indicate a person has Alzheimer’s or Parkinson’s.

As compared to healthy patients and ones with dementia caused by other conditions, those with both Alzheimer’s and Parkinson’s had seven times higher levels of the tau protein. People with Parkinson’s also had an eight times higher level of alpha-synuclein protein than the healthy control group.

Alzheimer’s disease is ranked as the sixth leading cause of death in the United States, and 5.4 million Americans are currently diagnosed with Alzheimer’s disease. Parkinson’s disease affects one million Americans, with at least 60,000 new cases reported annually each year.

“More research is needed to confirm these results, but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases. This also means tissue will be much more readily available for scientists to study,” said Rodriguez-Leyva. “This procedure could be used to study not only Alzheimer’s and Parkinson’s, but also other neurodegenerative diseases.”