New Imaging Technique May Aid Early-Stage Diagnosis of Parkinson’s, Study Says

brain imaging

A new imaging agent can efficiently reach the brain and bind toxic amyloid aggregates during early-stage Parkinson’s and Huntington’s disease, a study has found.

This opens a new approach to diagnose and evaluate the effectiveness of treatments for these neurodegenerative diseases.

The article, “ScFv-conjugated superparamagnetic iron oxide nanoparticles for MRI-based diagnosis in transgenic mouse models of Parkinson’s and Huntington’s diseases,” was published in Brain Research.

It is widely accepted that misfolded amyloidogenic proteins, alpha-synuclein, mutant Huntington protein, and amyloid-beta, are toxic species that play a role in the development of neurodegenerative diseases including Parkinson’s, Huntington’s, and Alzheimer’s diseases.

However, there are currently no conclusive diagnoses for the early stages of these neurodegenerative diseases.

Despite the differences in the makeup of amyloidogenic proteins and their associated diseases, these misfolded aggregates assembled from distinct amyloid proteins share general common structural features and mechanisms of toxicity. Therefore, antibodies targeting each specific misfolded amyloidogenic protein can be powerful tools for early diagnosis and treatment of several neurodegenerative diseases.

Over the past decade, molecular imaging — the visualization, characterization, and measurement of biological processes at the level of cells and molecules in humans and other living systems — has become a thriving field and offers potential tools for disease diagnosis.

Magnetic resonance imaging (MRI) techniques represent one of the best non-invasive molecular imaging methods and hold great promise for studying the brain.

The use of nanoparticles — tiny molecules — also is attracting increased attention due to their unique capacity to facilitate diagnostics and therapeutics. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) have attracted a great deal of attention for therapeutic delivery applications.

SPIONs consist of magnetic cores made of iron oxides coated with a biocompatible polymer that can be targeted to the required area through external magnets. The coating acts to shield the magnetic particle from the surrounding environment and also can be used to attach different types of molecules to increase their targeting capacity. These molecules then act as attachment points for the coupling of therapeutic molecules or antibodies to be delivered to the organ of interest.

SPIONs have been shown to penetrate the blood-brain barrier — a lining of cells that protect the brain from circulating molecules capable of damaging and disrupting neural function. When joined with an antibody that recognized amyloid-beta, SPIONs were successfully used to diagnose Alzheimer’s using MRI.

Although recent advances in molecular imaging techniques have improved the ability to diagnose other neurodegenerative diseases, Parkinson’s is still diagnosed mainly by a doctor’s observation based on motor symptoms including slowness of movement (i.e., bradykinesia), resting tremors, and muscular rigidity. For these reasons, researchers wanted to investigate whether SPIONs could be used to target amyloidogenic proteins in Parkinson’s disease and Huntington’s disease.

The team developed an amyloidogenic-targeted molecular MRI probe called W20-SPIONs. This imaging probe consists of an amyloidogenic-specific antibody known as W20 joined to SPIONs.

The researchers showed that these W20-SPIONs were stable, non-toxic, and specifically recognized alpha-synuclein oligomers in human cells and mice. Oligomers consist of a few units (or monomers) and are suggested to be the most toxic form of amyloid.

When applied to mouse models of Parkinson’s and Huntington’s, W20-SPIONs crossed the blood-brain barrier and specifically bound to the brain regions with amyloidogenic proteins, giving an MRI signal and distinguishing between mice with neurodegenerative disease from healthy controls.

These results indicate that W20-SPIONs have potential in early-stage diagnosis of Parkinson’s and Huntington’s disease and open a new strategy for assessing the effectiveness of new treatments for neurodegenerative diseases.

“In our study, W20-SPIONs showed sufficient signal sensitivity, good biostability, and no potential toxicity in vitro and in vivo, which also had the capacity of specially targeting oligomers in the brain,” researchers wrote.

“This evidence supports that W20-SPIONs were a successful oligomer-targeted MRI probe for early diagnostics of Parkinson’s and Huntington’s disease. Identification of reliable biomarkers of disease progression will play a key role in the diagnosis of neurodegenerative diseases, and also be important for the development and assessment of disease-modifying treatments,” they added.

Future studies will be required to show the safety and effectiveness of W20-SPIONs in the early-stage diagnosis of Parkinson’s disease and other neurodegenerative diseases in human patients.

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How to Use Computer Gaming as Therapy for Parkinson’s Disease

Computer Gaming

The brain is a plastic organ continually reshaping itself in response to the stimuli it receives and the way those stimuli are processed. The old adage “use it or lose it” applies even in the face of a challenging disease like Parkinson’s.

Computer gaming can help with brain training by exercising the brain to help moderate the effects of PD. For computer gaming to be efficacious as therapy, it must be implemented with careful attention to finding the right fit between the demands of the game and the therapeutic needs of the PD patient.

Recent research on video gaming and treatment for PD shows it can help with physical issues such as gait and balance.

The key to successfully using computer gaming is to find the right match of game for each person, as well as the appropriate difficulty level. The game must be challenging, but not so challenging that it becomes discouraging. It also must be rewarding and enjoyable. (There is that dopamine factor to consider.) Gaming has a “sweet spot,” like Goldilocks, in which you find just the right fit. I found this balance in the game “Shroud of the Avatar,” which I recommend for people with PD.

It took me a while to find the right video game — years, actually. “Shroud of the Avatar,” or “SotA,” is that game! It can be played at various levels. Not only can you find the sweet spot for your own style of playing, but also you can move that spot around depending on whether it is a good day or a bad day.

The game has a solid ethical foundation built on virtue and clean gameplay (no foul language). Playing SotA for 10 to 20 hours a week exercises the brain and the body — use it or lose it — while having a good time doing it.

SotA is just the right game for those with PD. It offers exercise for geographical memory, hand-eye coordination, speech, and problem-solving (scenario looping) at a variety of levels. It is a place where impulsivity can be applied with fewer consequences than in the real world. It is a place where the grouch can go when T.O.O.T.S. needs to be applied.

Have the urge to buy? Then earn virtual money and buy virtual things. Frustrated? Then enter the virtual world and work it out on some monsters. Have pain with your PD (a difficult problem for me)? Spend time in the virtual world of SotA to help manage the pain with less medication. Want a sense of accomplishment? Help build a community while also making yourself a strong avatar.

I have built a “sanctuary” for Parkinson’s folks inside SotA. It is a place where your avatar will find support and fellowship. Within this sanctuary is a place where you can find that sweet spot while contributing to building a support community. You can find this virtual sanctuary inside SotA in a town called Grumridge, just east of the city Aerie. You can see it on the map shown in the cover art of this column.

It may seem counterintuitive to say that fighting skeletons and building a virtual community is relaxing, but this has been my experience. Conversations I have had with others indicate that this experience is common. I often have clarity of mind while playing, and some of the ideas for these columns pop up in the middle of the game. That dopamine effect happens when successful within SotA, and the game offers many ways to experience success. You can’t get much better than having good, clean fun while slowing down the progression of PD!

One more note: I do use adaptive equipment to help me play the game. I have a large trackball on my dominant hand and a keypad with a thumb joystick on my other hand. You can see this illustrated in the cover art. It takes a little while to learn how to use this equipment, but the reward is a greater success rate inside the world of SotA (more dopamine!).

I also have a headset with a microphone. Plenty of opportunities exist to speak with others within the world of SotA, and the community of players is the best I have encountered in the gaming world. As far as I know, this is the first time a virtual support community within a game was developed for people with PD. Oh — and the game is free!

I look forward to seeing you there. My avatar name is Dr. Wiz. Let us build something special together.

PS: Thanks to the all the avatars (especially Ajumma Kim) and the game developers for their help building the Grumridge sanctuary.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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24-hour Levodopa-carbidopa Intestinal Gel Lessened Dyskinesia, Parkinson’s Study Finds

dyskinesia, levodopa-carbidopa intestinal gel

A 24-hour treatment with a levodopa-carbidopa intestinal gel (LCIG) lessened the duration and functional effect of dyskinesia — involuntary, jerky movements — in Parkinson’s patients, according to a small study.

The research, “24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease,” was published in npj Parkinson’s disease.

Continuous intra-jejunal (the middle part of the small intestine) infusion with a LCIG has been shown to efficiently treat Parkinson’s motor fluctuations. The gel normally is administered with a portable pump directly into the duodenum or upper jejunum by a permanent tube inserted surgically.

Currently, it is mainly used as a 16-hour per day continuous infusion, and is licensed for use in this way. However, additional benefits have been observed when used as a continuous 24-hour infusion in the treatment of severe nocturnal akinesia (losing the ability to move muscles voluntarily), daytime falls and freezing of gait (FOG), as well as poor sleep quality.

Clinical trials have shown that a 16-hour treatment with LCIG can effectively reduce levodopa-induced dyskinesia (LID), which typically occurs after long-term therapy, despite an increase in daily levodopa dose. Current treatments options for LID, such as deep brain stimulation and Gocovri (amantadine, by Adamas Pharmaceuticals) are not uniformly available or are not suitable for all patients.

Researchers from Movement Disorder Unit at Westmead Hospital, in Australia, have now described their clinical experience with a 24-hour LCIG infusion to treat dyskinesia in Parkinson’s patients.

Of 74 patients treated with LCIG for motor fluctuations, 12 (10 men) were treated with 24-hour daily infusion intended to control troublesome daytime dyskinesia and with sufficient data pre- and post- initiation of continuous treatment. Patients’ mean age at the start of 24-hour LCIG was 69 years and mean duration of Parkinson’s was 18 years. Two had a mutation in the PRKN gene, whose mutations are associated with the juvenile form of Parkinson disease.

Among these 12 patients, four took 24-hour LCIG infusion due to lack of response to 16-hour therapy; two due to troublesome dyskinesia and levodopa-unresponsive FOG; three due to levodopa-unresponsive FOG with non-troublesome dyskinesia; two more had troublesome dyskinesia and nocturnal akinesia; and one self-initiated 24-hour therapy. Two transitioned from oral levodopa, without an in-between 16-hour infusion.

Patients’ clinical characteristics, as well as dyskinesia severity and incidence, were analyzed before and after therapy using the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) – part 3, part 4 (motor complications) total scores and sub-scores 4.1 (time spent with dyskinesias) and 4.2 (functional impact of dyskinesias). All evaluations were performed at baseline and at six months after starting 16- and 24-hour LCIG.

Daytime dyskinesia was reduced in nine patients (75%) following 24-hour therapy, including seven who were first treated with 16-hour infusion and the two patients who transitioned from oral levodopa.

Of the three patients without decrease in dyskinesia, one could not tolerate 24-hour infusion due to worsening of hallucinations and agitation, and shifted back to 16-hour therapy after two months. After six months, the patient’s neurocognitive function returned to baseline. A second 24-hour therapy was initiated 11 months later, but again led to no benefit. The remaining two patients had no change in dyskinesia despite eased FOG and nocturnal akinesia.

Combining the results from all 12 patients, both the time spent with dyskinesia and its functional impact were reduced during 24-hour LCIG treatment. In contrast, the MDS-UPDRS part 3 “ON” scores — control of motor symptoms — did not change.

Five patients showed lessened dyskinesia despite an overall increase in the total daily levodopa dose. No patient had worsened dyskinesia after a median follow-up of 27.5 months.

A total of three patients had worsening of nocturnal hallucinations, which diminished after lowering the night-time LCIG continuous rate. One patient developed asymptomatic peripheral neuropathy (nerve damage) within six months of 24-hour therapy, which remained stable during 18 months of follow-up.

Ten patients experienced vitamin B6 deficiency requiring supplementation, while seven developed vitamin B12 deficiency during therapy (16- or 24-hour). Two patients had hyperhomocysteinaemia (excess blood level of homocysteine), a condition associated with cardiovascular problems and neuropathy.

Of note, no patient elected to return to 16-hour infusion due to difficulty managing the pump, or technical difficulties with the jejunal tube.

Overall, if future studies confirm these findings, “24-[hour] LCIG may offer a novel approach to the treatment of troublesome dyskinesias which persist despite an adequate trial of 16-[hour] therapy,” researchers wrote.

Although further research is necessary to assess the mechanisms involved, the researchers hypothesized that the benefits with 24-hour treatment in patients not responding to 16-hour infusion may be due to continuous levodopa delivery to the brain.

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Canadian Groups Launch Large-scale Initiative to Capture Data on Parkinson’s Patients Nationwide

Canadian Parkinson's survey

Parkinson Canada and Brain Canada have recently launched the Canadian Open Parkinson Network (C-OPN), the first platform to include data from people with Parkinson’s disease across the country and facilitate access to researchers studying the disease.

Supported by a $2 million grant, the C-OPN will include a national patient registry along with a database that has extended clinical information — data from diagnosis (including magnetic resonance imaging and positron emission tomography scans), patients’ motor and cognitive parameters, and records of sleep, behavioral, and neuropsychological analysis.

Additionally, the C-OPN will operate as a biobank, or a repository for patients’ biological material — blood samples and DNA — for researcher access.

“The Canadian Open Parkinson Network is a major initiative that will keep Canada at the leading edge of Parkinson’s disease research. By building a strong, interconnected and collaborative network of researchers, physicians and people living with Parkinson’s, we can work strategically to accelerate advancements in Parkinson’s research and treatment,” Oury Monchi, PhD, said in a press release.

Monchi will serve as the director and principal investigator of the C-OPN. He is also the clinical research director at the Hotchkiss Brain Institute, Cumming School of Medicine at the University of Calgary.

“Brain Canada is pleased to be a partner with Parkinson Canada on the Canadian Open Parkinson Network. This program follows the establishment of the Canadian Open Neuroscience Platform, a national effort we initiated to link data across the country, and standardize how we collect, store and analyze this data,” said Inez Jabalpurwala, president and CEO of Brain Canada.

“The Parkinson registry and database will create the first national platform to capture data from those living with Parkinson’s, and make the data accessible to a wider number of researchers. The goal is to accelerate our already excellent Parkinson’s research in Canada, resulting in better patient outcomes,” ‎ Jabalpurwala added.

The C-OPN hopes to build capacity and increase awareness among government, healthcare professionals, researchers, health charities and the general public.

“With more than 25 people diagnosed each day, we are reminded why establishing the Canadian Open Parkinson Network is critical now. It brings hope for a cure, and accelerated treatments over the next ten years and beyond, and it involves the very people whom researchers are trying to help,” said Joyce Gordon, CEO of Parkinson Canada.

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Plant Compound, Arbutin, Eases Some Symptoms in Parkinson’s Mouse Model, Study Shows

arbutin plant compound

Arbutin, a natural compound found in plants such as bearberry leaves and pear trees, was able to protect dopaminergic neurons and reduce behavioral deficits and oxidative stress in an animal model of Parkinson’s disease, a study reports.

The study, “Arbutin attenuates behavioral impairment and oxidative stress in an animal model of Parkinson’s disease,” was published in the Avicenna Journal of Phytomedicine.

Parkinson’s disease is characterized by the progressive deterioration and death of a specific subset of brain cells called dopaminergic neurons. The loss of these nerve cells causes the disease’s neurological symptoms such as tremors, muscle rigidity, slow movements, and postural instability.

However, the molecular mechanisms by which these dopaminergic neurons are selectively affected and degenerate over time remains unknown.

Increasing evidence shows that oxidative stress is an important factor that contributes to disease progression.

Oxidative stress is caused by an imbalance between the body’s production of potentially harmful reactive oxygen species and the ability of cells to detoxify them. These reactive oxygen species can damage crucial molecules in cells including DNA and proteins, hampering their function and ultimately their ability to survive.

Current treatment options for Parkinson’s are still limited, losing effectiveness over time and often associated with side effects including nausea, fatigue, fainting, and increased tremors. Therefore, new therapeutics are urgently needed.

In this study, researchers investigated the effectiveness of a new compound — arbutin — in the treatment of Parkinson’s disease. Arbutin is naturally found in various plants, such as bearberry leaves and pear trees.

The team used a mouse model that mimics the symptoms and molecular alterations of the human disease. Mice were injected with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP), known for inducing Parkinson’s symptoms similar to those observed in human patients.

Animals were divided into three groups — a control group injected with a saline (innocuous) solution; a second group treated with a saline solution for seven days, followed by MPTP, injected into the abdomen; and a third group receiving arbutin (50 mg/kg) injected into the abdomen, before receiving MPTP injections.

On the 14th day of the experiment, researchers evaluated behavioral deficits using a locomotion test, hanging wire test, and forepaw stride length. They also analyzed the animals’ blood and brain tissue.

Arbutin-treated animals improved their locomotor activity and increased their forepaw step distance over the controls. Treated animals were also able to hand upside down (hanging wire test) for longer periods of time than the controls.

Arbutin also reduced blood and brain levels of specific molecules associated with oxidative stress, such as nitric oxide, previously shown to promote the death of dopaminergic neurons. The expression of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress whose levels were reported to be higher in the brains of Parkinson’s patients, was also reduced, both in the brain and blood of arbutin-treated animals.

These findings suggest that “arbutin can effectively attenuate behavioral deficits and reduce oxidative and nitrosative stress in MPTP- induced PD [Parkinson’s] model,” the researchers wrote.

They are now interested in clarifying “the exact molecular mechanisms by which arbutin can protect dopaminergic neurons.”

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PF-06412562 Safe, Eases Motor Impairments in Parkinson’s Patients, Phase 1 Trial Finds

PF-06412562, Phase 1

A compound that targets two specific dopamine receptors in the brain is safe and can ease motor deficits in Parkinson’s patents, recent clinical data reveals.

The study, “Evaluation of D1/D5 Partial Agonist PF-06412562 in Parkinson’s Disease following Oral Administration,” was published in Neurodegenerative Diseases.

Pharmacological treatment of Parkinson’s patients mostly has used the dopamine precursor levodopa and agonists (activators) of dopamine D2 receptors.

Dopamine receptors can be divided into two classes (D1-like and D2-like) on the basis of their biochemical and physiological effects and are a target of action for different therapeutic compounds. Dopaminergic neurons can regulate movement via the activation of these receptors.

Long-term administration of levodopa, however, may lead to the development of motor complications, including dyskinesia (involuntary, jerky movements).

The potential benefit of selective D1 agonists is not as well-characterized. Although early studies have suggested little anti-parkinsonian potential in primates or humans, later research with different compounds indicated comparable effectiveness to levodopa in Parkinson’s patients with dyskinesia.

However, D1 agonists’ blood pressure-lowering (hypotensive) effects, low oral bioavailability (the proportion that reaches systemic circulation) and short half-life (the time required for the agonist’s amount in the body to be reduced by half) have limited their development.

Researchers now hypothesized whether selective D1 partial agonists, which are less effective than full agonists, may be an alternative or add-on treatment to manage Parkinson’s symptoms.

Researchers at Pfizer designed a double-blind, Phase 1 study (NCT02006290) that assessed PF-06412562 — a partial agonist of  the D1 receptor — for motor benefit in Parkinson’s patients. Safety, tolerability and pharmacokinetics (how the body affects a medicine) of PF-06412562 also were evaluated. Of note, this partial agonist also binds to D5, another dopamine receptor that is very similar to D1.

Selective partial D1/D5 stimulation was predicted to ease several motor symptoms, including dyskinesia.

The safety and effectiveness of a single, oral dose of PF-06412562 was tested at four U.S. sites in 19 Parkinson’s patients — 42% men, all white, mean age 63.8 years, and mean disease duration 6.7 years.

Maximum percent improvement in finger-tapping speed — assessed with the Kinesia technology — was the study’s primary goal. Because  this measure still requires validation, change from baseline in Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale – Part 3 (MDS-UPDRS-III) also was analyzed to assess change in motor symptoms.

Patients received Merck’s Sinemet (25 mg of carbidopa and 100 or 250 mg of levodopa), PF-06412562 in 5 mg tablets, or placebo in the morning following an overnight fast and no Parkinson’s medications after 8 p.m. the previous night.

Thirteen patients received a second 30 mg dose of PF06412562 (plus 20 mg four hours later), or placebo four hours after the first dose. Each patient served as his/her own control.

With this split-dosing scheme, researchers intended to increase the length of time patients spent at projected efficacious levels without going over the exposure limit.

The maximum dose of PF-06412562 was 30 mg, which was well-tolerated by healthy volunteers in a previous study and led to maximum plasma levels shown to induce motor benefits in primates.

Treatment with PF-06412562 did not improve finger-tapping speed (a measure of slowness of movement, or bradykinesia), which scientists attributed to inconsistencies in the task that led to large fluctuations of baseline values.

In contrast, patients receiving PF-06412562 showed statistically significant lessening of motor symptom severity as assessed via change from baseline in MDS-UPDRS-III score at 1.5-2.5 hours post-dose, compared to placebo. This clinically meaningful improvement gradually decreased over 12 hours.

Median peak concentration of PF06412562 and its by-product — PF-06663872 — in plasma was reached at approximately one hour post-treatment and 5.1 hours post-split doses, respectively. In turn, levodopa reached peak concentration at approximately 30 minutes after a single oral dose.

“The observed PK indicate that PF-06412562 is suitable for once-daily or twice-daily oral administration,” researchers wrote.

All adverse events (AEs, or side effects) were mild-to-moderate and did not lead to any treatment discontinuation or dose reduction. Five participants receiving PF-06412562 30 + 20 mg experienced seven treatment-emergent AEs. Nausea and fatigue were the most common.

“This study demonstrates the potential for further studies to explore the efficacy and safety of an orally available D1/D5 agonist in the improvement of motor deficits in patients with [Parkinson’s] in an acute-treatment setting,” researchers concluded.

Of note, three of the study’s authors are employees of Pfizer. Two others are former employees.

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Staying Active Versus Exercise

exercise in Parkinson's

Sherri Journeying Through

Whether you ask a group of people with Parkinson’s disease (PD) or your neurologist about the best thing you can do to keep PD at bay or slow down its symptoms, the most common response will likely be “exercise.” Some may say, “Stay active.” But do you realize that staying active and exercising are two different things?

Just about anyone can exercise — jumping jacks, touch your toes, jog around your living room, lift a couple of cans of green beans — but it takes sheer determination to stay active when you are battling a little monster like Parkinson’s disease.

Being active involves more than movement on your part. It includes a state of mind to persevere, to keep putting one foot in front of the other, and to not give up even when you feel like quitting. Being active involves a positive outlook.

It is easy to fall into a state of apathy or depression when fighting a chronic illness, but to try to pull yourself out of one can be downright hard. The gray cloud of despair can last days, weeks, months, even years. Staying active can help sidestep those dark times.

Sitting and watching television can sound relaxing, but when flopping on the couch is your go-to place when you’re feeling down, it may take an act of God to get you back up. Depression feeds depression. Apathy feeds depression. At times you will have to force yourself up off that couch and do something. But force you must. You must stay active. You must not allow yourself to succumb to dark days. Fight and fight hard. Get your friends to join you by coming alongside them. Show them you need them because they do want to be needed at this time in your life.

Exercise is essential for a Parkinson’s patient. Walking, boxing, bicycling, tai chi — these are all terrific forms of exercise as you strive to live healthily with PD. However, to determinedly exercise with PD, you have to “master” staying active. Keep your mind on an even and positive keel. You must tell yourself that you can do this thing; you can battle this little monster. You must say to yourself that as this disease strives to master you, you will fight tooth and nail to push forward and stay active.

Following are some techniques I use in my battle to master PD:

  • Keep your mind active. Do word puzzles, jigsaw puzzles, sudoku games, and more to keep your mind alert.
  • Don’t give in to fear. 
  • Make positive thinking a habit. Carry scripture verses or positive thinking quotes in your pants pocket and read them throughout the day.
  • Don’t give up and don’t give in: mentally, physically, relationally, emotionally, or spiritually.
  • Avoid temptations like empty couches and TV remote controls.
  • Fight the dark days. Don’t let them get the upper hand.
  • Don’t go it alone. Get connected via a support group.

I am in no way an expert in “staying active” but I do make a valiant effort to do so. I have found the above practices to be helpful in dealing with Parkinson’s and hope they are useful to you too.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Study Links Smoking, Reduced Parkinson’s Risk, But Comes with Caveat

Parkinson's and smoking

Smoking more cigarettes or for a longer time is associated with a decreased risk of developing Parkinson’s, according to a population-based study.

A reduced risk was also seen in people exposed to passive smoking compared with those who had never smoked.

However, the scientists cautioned that rather than encouraging people to smoke, the findings warrant further research into which compound in tobacco confers this effect.

The study, “Exploring causality of the association between smoking and Parkinson’s disease,” was published in the International Journal of Epidemiology.

The link between smoking and a reduced risk for Parkinson’s is supported by substantial evidence in men and women, and has included cigarette, pipe, and cigar smoking, as well as using smokeless tobacco. Also, children of smokers have shown a lower risk for developing the disease.

However, researchers have recommended considerable caution in interpreting this association as protective. They have been studying a potential effect of personality, in particular whether a low-risk-taking personality would be a confounder, especially if induced by dopamine shortage — a Parkinson’s hallmark — which may make it easier to quit smoking. In this regard, a link between passive smoking and protection from Parkinson’s — which is not susceptible to different personalities — could not be determined.

To better understand this correlation, researchers from Queen Mary University of London, Imperial College London and University of Campania Luigi Vanvitelli, in Italy, analyzed the link between Parkinson’s risk and smoking duration, amount and time since quitting smoking. They looked at a potential delaying effect, smoking patterns among current and former smokers, the association with passive smoking, and the consistency across clinical subtypes.

The study included 220,494 people participating in NeuroEPIC4PD, a prospective European population-based study in 13 centers from eight countries. A total of 715 cases of Parkinson’s (mean age at recruitment 61.4 years, age at onset 67.5) were analyzed.

Data on smoking habits were collected at recruitment, including whether participants were never, former or current smokers, their age when they started smoking and when they quit, and number of cigarettes per day at different ages.

The results showed that, compared with people who had never smoked, former smokers had a 20% lower risk and current smokers a halved risk for developing Parkinson’s during follow-up (12.8 years).

Smoking more cigarettes and for a longer period of time were also associated with a lower risk of developing the disease, as the risk in people smoking 12 or more cigarettes a day or for longer than 30 years was about 55% lower compared to those who had never smoked.

Smoking correlated with reduced disease risk in both mid-age and late-onset Parkinson’s, as well as in tremor-dominant and akinetic-rigid (slowed movement, muscle stiffness, postural instability, gait impairment) Parkinson’s. Also, the risk did not vary over the follow-up period, which argues against a delaying effect of smoking on Parkinson’s onset, the team observed.

Exposure to passive smoking at home or work was also linked to lower risk, as passive smokers were 30% less likely to develop the disease than non-exposed individuals.

“In conclusion, the present findings are consistent with a protective effect of smoking on the risk of [Parkinson’s],” scientists stated.

“Our discovery is incredibly important from a scientific point of view and should prompt basic science research aimed at identifying the agent responsible for this effect found in tobacco,” Valentina Gallo, MD, PhD. the study’s first author, said in a press release. “Hopefully this will give insight for preventive treatment options.”

“However, no one would ever be advised to use smoking as a preventive treatment for Parkinson’s based on this research, because of the disastrous effects we know smoking has on people’s general health,” Gallo added.

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Discovery of New Brain Region Could Have Implications for Neurodegenerative Disorders

new brain region

The recent discovery of a previously unknown region of the human brain could have significant implications for neurodegenerative disorders affecting motor skills, such as Parkinson’s disease and motor neuron diseases including amyotrophic lateral sclerosis and spinal muscular atrophy

Neuroscientist George Paxinos’ discovery of the endorestiform nucleus, which functions to control fine motor skills, is detailed in his new book, “Human Brainstem: Cytoarchitecture, Chemoarchitecture, Myeloarchitecture,” and published in Elsevier.

An increasingly detailed map of the brain and spinal cord has been essential to most major discoveries in neuroscience in the past century. In the book, Paxinos and colleagues from Neuroscience Research Australia (NeuRA) present the first detailed atlas of the human brainstem — the back section of the brain that is continuous with the spinal cord — in over twenty years.

“I am a brain cartographer and the maps I do are of the normal, the canonical brain, and other scientists can compare their pathological tissue if they study Alzheimer’s disease, Parkinson’s, epilepsy tissue obtained from post-mortems against the canonical brain,” Paxinos said.

The researchers took advantage of new imaging technology that allows for the brain to be studied in live, conscious individuals. Although the imaging resolution has room for improvement, researchers still had the advantage of imaging the brain in its natural location as opposed to removing it and processing it for imaging post-mortem, which distorts the results and, ultimately, identification of brain regions. This new, live imaging technology allowed researchers to identify structures and more accurately map them to specific areas in the brain.

When constructing a new map of the human brainstem, the team identified a region formerly unknown to science. They found that the endorestiform nucleus is in a part of the brain called the restiform body or inferior cerebellar peduncle, which connects the cerebellum — the back of the brain — to the underlying brainstem. The restiform body is known to regulate fine motor skills by integrating information about a person’s surroundings and movements.

Previously, the region was not identified as its own nucleus — a group of nerve cells located deep inside the brain and brainstem that have similar connections and functions. The researchers now say it is a different area from its surroundings.

An initial observation of the region was made years ago in patients who underwent a therapeutic anterolateral cordotomy — a surgical procedure that deactivates selected pain-conducting pathways in the spinal cord to alleviate pain.

This procedure is commonly performed on patients experiencing severe pain because of cancer or other  diseases. It was observed that some of the pathways that were severed in the spinal cord because of the procedure connected to this sub-region in the restiform body in the brainstem.

The brain region has not been found in several monkeys that are very closely related to humans, making it possibly exclusive to humans and possibly holding clues as to what makes us unique.

“One intriguing thing about this endorestiform nucleus is that it seems to be present only in the human; we have not been able to detect it in the rhesus monkey or the marmoset that we have studied,” Paxinos said. “I can only guess about its function but given the part of the brain where it’s found, the highway that connects the spinal cord to the cerebellum, it might be involved in fine motor control that humans are so good at. It would be hard to imagine a chimpanzee playing the guitar dexterously even if it liked to make music.”

Sample images and 3D animations of the brain can be seen here and Paxinos can be seen explaining his discovery here.

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Exercise That Motivates Parkinson’s Patients to Push Limits Can Offer Range of Benefits, Experts Say

exercise in Parkinson's

With a treatment not yet within reach that might slow the progression of Parkinson’s disease, much less offer a cure, many — doctors, patients, and researchers alike — are looking to exercise in hopes of fending off a worsening of symptoms.

Interest in exercise-based interventions has risen so much that “the number of publications on exercise studies has increased by a factor of 10 since 2000,” Tanya Simuni, MD, chief of Movement Disorders in the Department of Neurology at Northwestern University, said in a 2016 interview on the International Parkinson and Movement Disorder Society website.

Many consider it common sense that exercise can help to compensate for the motor symptoms that mark Parkinson’s — and research points to this possibility — yet scientists still have few clues as to how exactly it does so.

Work done through the Parkinson’s Outcome Project, an ongoing study involving more than 12,000 patients in five countries, suggests that patients should exercise at least 2.5 hours each week to slow decline and maintain a better quality of life. A similar study advised that patients should begin regular exercise at diagnosis.

Still, this research stops short of recommending a specific exercise regimen as a best strategy.

This has led several enterprises — both for-profit companies and nonprofit groups —  to offer classes ranging from dancing to Parkinson’s-only boxing, and products such as specialized at-home exercise equipment that promise to reduce, reverse, and delay symptoms.

While the literature on exercise in Parkinson’s is “extensive,” Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson’s Disease Association and a practicing neurologist, told Parkinson’s News Today, studies on its effects are typically small. Only recently have they begun to grow in size and in quality — but “translating [their findings] into practical recommendations” is a challenge.

Exercise and the brain

In Parkinson’s, neurons in a brain area called the substantia nigra that are responsible for producing a neurotransmitter called dopamine gradually die off, leading to motor symptoms such as tremor and bradykinesia (slow movement).

Levodopa — which works to increase dopamine levels in the brain but cannot rescue damaged neurons — is currently the front-line treatment for the disease.

Some evidence suggests that, like levodopa, exercise may exert some of its effects by increasing dopamine. A recent study of 17 Parkinson’s patients used positron emission tomography (PET) scans of the brain before and after stationary cycling. Results showed that habitual exercisers in this group — eight patients who exercised more than three hours a week — had higher dopamine levels in the dorsal striatum (the brain area that receives dopamine input from the substantia nigra to help control movement) after stationary cycling than the nine others who were sedentary.

The eight exercisers also performed better on functional tests assessing motor symptoms, including the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 — which measures items such as gait and time to stand — and in tests of non-motor symptoms such as apathy and depression.

Exercise might also go a step further than levodopa by increasing brain-derived-neurotrophic-factor (BDNF), which promotes the survival of neurons that make dopamine — the same neurons that degenerate in Parkinson’s patients.

An analysis of 12 studies of BDNF levels in Parkinson’s patients found lower levels of BDNF in patients’ serum than in healthy individuals (mean difference of 2.99 ng/mL).

Two of these studies showed that patients who completed exercise programs lasting four, eight, or 12 weeks increased both serum levels of BDNF and UPDRS motor scores.

A separate review of 32 studies related to exercise’s effects on BDNF suggested that aerobic exercise increased BDNF serum levels in healthy people. This was seen to be both an acute effect of a single exercise session and a result of consistent exercise. Strength training did not impact BDNF.

Another Phase 2 study (NCT01506479) divided 128 recently diagnosed patients into three groups that either continued not exercising, participated in 30 minutes of gentle treadmill walking four times a week, or were assigned to six months of high-intensity treadmill exercises for 30 minutes four times a week. Those who did the high-intensity workout maintained the same UPDRS motor score at the study’s end as they had at its start, while those in group that did not exercise saw their scores drop by three points, and those who exercised minimally had a two-point drop.

Rock Steady Boxing

Rock Steady Boxing, a nonprofit, non-combat boxing program designed exclusively for Parkinson’s patients, aims to help all — regardless of skill level — take advantage of the benefits of exercise, while building a supportive and understanding community of patients.

Parkinson’s News Today columnist Jean Mellano, an athlete who not only boxes with Rock Steady but also does physical therapy, yoga, weight training, and daily walking to help treat her Parkinson’s, said “the camaraderie is off the charts.”

Joyce Johnson, Rock Steady’s executive director echoed that sentiment, noting “the magic of Rock Steady is the camaraderie and the fact that all of our boxers are fighting back against same disease.”

Founded in 2006, Rock Steady Boxing has grown in popularity and now operates out of more than 700 locations worldwide.

“We’ve actually had neurologists write Rock Steady Boxing on their little prescription pad and sent them to a location,” Johnson said.

Rock Steady allows affiliates to operate for a small fee in boxing gyms, YMCAs, hospitals, and churches. Some programs are free to patients thanks to grants, but most require participants to pay fees similar to that of an average exercise program.

A typical 90-minute class begins with a warm-up, followed by varied exercises designed to mitigate Parkinson’s symptoms through balance and flexibility work, jumping rope, weightlifting, and, of course, boxing.

A case study, listed on the group’s website and published in the journal Physical Therapyof six Rock Steady boxers showed that after 24-36 classes over the course of 12 weeks, all six boxers improved in at least five out of 12 outcome measures, such as the Functional Reach Test, gait speed, cadence, stride length, step width, and other measures of UPDRS part 3, as well as the Parkinson Disease Quality of Life Scale, an assessment of non-motor symptoms. Patients in earlier disease stages did better at 12 weeks, but those with more advanced disease gained benefits with regular classes that ran for 24 and 36 weeks.

Stephanie Combs-Miller, PhD, the case series’ lead author and an associate professor at the Krannert School of Physical Therapy at the University of Indianapolis, published a slightly larger study in 2013 comparing Rock Steady Boxing with a community-based exercise program that included stretching, resistance, aerobic, and balance-based exercises in 31 patients.

Patients again took part in 24-36 sessions of either workout over the course of 12 weeks. The researchers expected that both programs would lead to improvements, but that the boxers’ improvements would be more dramatic than those of patients in the traditional exercise program.

However, Combs-Miller and her team concluded that “both groups demonstrated significant improvements with the balance, mobility, and quality of life,” supporting the idea that any group-based exercise can help Parkinson’s patients, provided they do it consistently.

Still, as Johnson put it: “How much more fun is that for a grandpa to tell his grandkids that he’s going to boxing instead of saying he’s going to therapy?” 

Theracycle and forced exercise

Rock Steady boxers are encouraged by coaches and peers to attempt moves and workout intensities that seem to push the limits of their abilities.

The Theracycle takes this idea a step further, using a motor that forces patients to pedal the stationary bike faster than they could on their own, theoretically maximizing workout effects.

Jay Alberts, PhD, a biomedical engineer at the Cleveland Clinic and an avid cyclist, went on a 200-mile trip in 2003 on a tandem bike with a friend, who also happened to be a Parkinson’s patient. The friend was forced to pedal at Alberts’ pace, which was about 30 revolutions per minute faster than she would have been able to pedal on her own.  According to Alberts, her tremors disappeared during the ride and for a period of time afterward. 

Alberts brought another patient on his tandem bike and noticed similarly striking results. 

But requiring a strong cyclist to take patients out on tandem bike rides regularly is not a practical treatment plan for 10 million patients worldwide.

The Theracycle, a motorized stationary bicycle based on the exercycle invented in 1932, gives patients a safe way to engage in forced exercise — exercise where, in this case, a motor helps them pedal at a speed they wouldn’t be able to reach on their own — at home without a tandem bike or partner.

Alberts conducted a small study in 2009 at the Cleveland Clinic, which appears on the Theracycle website and was published in the journal Neurorehabilitation and Neural Repair, comparing the effects of forced exercise and voluntary exercise (in which patients choose the intensity at which they exercise) on Parkinson’s symptoms.

Ten patients were randomly assigned to complete three one-hour sessions per week of either voluntary cycling or forced exercise using a motorized cycle. After eight weeks, both groups showed improved aerobic capacity, but only the forced exercise group showed improvements (an average of 35%) on the UPDRS part 3.

Mike Studer, president and co-owner of Northwest Rehabilitation Associates, has been using the Theracycle in his Oregon physical therapy clinic since the company reached out to him more than eight years ago, shortly after the Cleveland Clinic study was published. He said he “remained skeptical” of the new research at first, but that the Theracycle “meets and exceeds” expectations.

His clinic also offers the Rock Steady Boxing program, yoga, treadmills, underwater exercises, and more. Studer says “a repetition is not equal to every other repetition.” With the Theracycle, he can control the intensity of a patient’s workout, a crucial factor in its effectiveness.

The main drawback of the machine is its price. It’s not covered by Medicare, and Rich Blumenthal, chief operating officer of Theracycle, admits that the $3,700-$5,900 price tag (depending on the model) can make the equipment difficult to sell. But patients’ lives “are just better when they start using this,” he says.

Both regimens have one thing in common — pushing patients to do more than they may think they are capable of doing.

“There is nothing wrong with people’s bodies. What’s wrong is that neurologically they quit producing dopamine,” Johnson said.

Whether they are encouraged by coaches or by motors, patients often end up doing more than they ever thought they could.

We may never know which exercise regimen is the most effective for preventing Parkinson’s decline, or which is better for any given patients.

“It’s virtually impossible to imagine testing every single modality versus every other modality,” Gilbert said, but “the answer is it’s probably a little of everything.”

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