'Walk and think' test could be key to concussion care

June 28, 2018

Successfully performing that simple test of cognition could help decide whether a concussed athlete is safe to return to play, new research shows.

If the athlete can't simultaneously walk and think in this way, they may not be fully recovered from a concussion and could be at risk for another injury if they resume playing sports, the researchers found.

"If we can determine that athletes have recovered this ability after concussion, they may be less likely to get re-injured," explained study lead author David Howell. He's an athletic trainer and lead researcher for the Sports Medicine Center at Children's Hospital Colorado, in Aurora.

As his team explained, young athletes who've had a concussion are typically given the green light to return to sports if they pass tests that assess balance, vision, movement, and the ability to think and reason.

But some experts believe those tests might not detect continuing problems that could still increase the risk of another injury.

The new study included 41 male and female high school and college athletes who suffered a concussion while playing basketball, football, hockey or soccer, but eventually returned to play.

The athletes were given what's known as a "dual-task gait test," which measures the ability to walk and think at the same time. In the test, a person would be asked to walk normally while completing a mental task spelling a word backwards, reciting the months of the year in reverse order, or subtracting by 7's beginning at 99.

Dual-task gait tests have long been used to monitor patients with progressive brain diseases such as Parkinson's and Alzheimer's.

The athletes in the new study were tested in this way three weeks after their concussion and again when they were given the OK to return to play.

The study seemed to show that scores on the dual-task test did reflect potential cognitive damage. Within a year of returning to play, 15 of the athletes suffered another injury, Howell's team noted—four had another concussion and others had knee dislocations, or hip or ankle sprains. Between their first and second dual-task gait tests, the injured athletes' scores fell, but there was no change among the non-injured athletes.

The study was presented Thursday at the National Athletic Trainers' Association (NATA) meeting, in New Orleans. Because the findings haven't yet been published in a peer-reviewed journal, they should be considered preliminary.

Still, the findings suggest that "walk and think" tests might be an important addition to the protocol for determining when an athlete can return to play after a concussion, the researchers said.

"Athletic trainers are concerned about the safety of athletes and, along with coaches and parents, want to be sure these students are fully healthy before they return to play," Howell said in a NATA news release. 

"Our study is the first to test the theory that subsequent injury risk is related to motor function and/or attentional deficits, which can be measured using dual-task tests," he added.

"This early research sheds light on the complexities of the recovering brain and suggests that dual-task gait may be a paradigm worth looking at to reduce the risk of injury before clearing an athlete to return to play," Howell said. "The next step is to translate this research into something athletic trainers can easily use to assess athletes."

Two experts in concussion care agreed that the findings could help keep injured athletes safe.

The study findings "suggest that the currently used criteria used to determine 'return to play' may be inadequate," said Dr. Raj Narayan, chair of neurosurgery at Long Island Jewish Medical Center in New Hyde Park, N.Y.

Rosemarie Basile, a neuropsychologist at Staten Island University Hospital in New York City, agreed.

"Even once an athlete has been deemed recovered [from concussion] and cleared to return to sports, subtle symptoms can remain that may pose a risk for future injury," said Basile, who directs psychological services at the hospital.

The "walk and think" test "serves as a kind of brain 'stress test," Basile explained. And while the study population was small, she said the findings "highlight the need for continued research on more sensitive methods for predicting who may be at risk for further concussion."

More information: The American Academy of Family Physicians has more on concussion. 

https://medicalxpress.com/news/2018-06-key-concussion.html

Study provides promise in search for simple, early test for Alzheimer's disease

 June 28, 2018, Indiana University

MicroRNA 142, in green, shown in neurons in the brain. The molecule may represent a potential biomarker to diagnosis or predict dementia. Credit: Hui-Chen Lu, Indiana University

Researchers at Indiana University have found early evidence that tiny snippets of genetic material called microRNA may help with early detection of conditions such as Alzheimer's disease.

The study, published June 18 in Scientific Reports, found that changes in microRNA are detectable in mice long before they start to show symptoms from neurodegeneration. These microRNA changes may represent an early warning sign, or "biomarker," for the condition.

"Identifying biomarkers early in a disease is important for diagnosing the condition, and following its progression and response to treatment," said Hui-Chen Lu, a professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences, who led the study. "You need something that can predict your future."

There is currently no treatment to stop or reverse the effects of neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS or Huntington's. It's also estimated that Alzheimer's disease alone, which is the most common of these disorders, will affect 14 million Americans and cost taxpayers $1.1 trillion by 2050.

Unlike regular "messenger RNA," which direct cells to produce specific proteins, microRNA plays a regulatory role, increasing or decreasing the number of proteins that messenger RNAs encode. A single snippet of microRNA can impact the function of tens or hundreds of proteins in the body.

Due to their stability in urine and blood, there is growing interest in using microRNA as biomarkers for disease prediction and diagnosis. Lu's study is an early step to learn whether microRNA can be used to detect neurodegenerative disorders.

To explore this question, Lu and colleagues analyzed microRNA and messenger RNA in two groups: a healthy group and a group genetically modified to develop symptoms of dementia. The team found the highest level of "dysregulation"—or deviation from normal levels—in the microRNA of the dementia group before their physical symptoms developed.

"Higher levels of pre-symptomatic microRNA dysregulation are significant because it strongly suggests that it may have a role in changes in the brain in later stages," Lu said.

The team then compared the microRNA changes to the messenger RNA changes to identify biological pathways affected by microRNA dysregulation. Their analysis suggested that changes in microRNA affected pathways related to immunity in the dementia-prone model.

In response, the team then conducted additional tests to study a specific type of microRNA that was elevated in the dementia model. The microRNA—called microRNA 142—is known to play a major role in inflammation, a part of the immune response.

They found that introducing this microRNA into the brain triggered a significant neuroinflammation. The result is important since many other studies have shown that chronic inflammation contributes to many types of disease, including neurodegeneration, Lu said.

She added that the next step will be to learn whether microRNA 142 is easily detectable through a blood test, a key quality for a truly non-invasive biomarker.

More information: Salil Sharma et al, Presymptomatic change in microRNAs modulates Tau pathology, Scientific Reports (2018).  DOI: 10.1038/s41598-018-27527-6 

Journal reference: Scientific Reports

Provided by: Indiana University 

https://medicalxpress.com/news/2018-06-simple-early-alzheimer-disease.html

Biochemists follow clues toward Alzheimer's, cancer, longevity

 June 28, 2018, Rice University

In microscopic images of muscle tissue from normal fruit flies (left), fluorescent tags reveal uniform levels of the structural protein actin (blue) and almost no poly-UB, a protein aggregate that is broken apart and recycled by healthy cells. In muscle tissue from flies lacking HSP gene activity (right), actin levels are reduced and cells contain a toxic buildup of poly-UB. Credit: James McNew/Rice University

James McNew's and Michael Stern's biochemical hunt for the root cause of a rare, paralyzing genetic disorder is a 10-year quest that's taken an unexpected turn toward everyday killers such as Alzheimer's disease, cancer and aging.

The National Institutes of Health has awarded the Rice University scientists a five-year R01 grant to investigate a biochemical domino effect that begins with a critical regulatory protein called TOR and ends with cells dying of oxidative stress. TOR regulates cell growth and survival and only recently became a focus for Stern and McNew, professors of biochemistry and cell biology in Rice's Department of BioSciences and co-investigators on the $1.9 million grant from the NIH's National Institute of Neurological Disorders and Stroke.

"It's known that TOR controls starvation in virtually every animal, including humans," McNew said. "Decreased TOR activity has even been found to increase the life span of yeast, worms and fruit flies, and some studies have found that TOR-inhibiting drugs increase the life span of mice. Increased TOR activity is also involved in cancer and has been implicated in Alzheimer's, Parkinson's and other neurodegenerative diseases, including one called hereditary spastic paraplegia (HSP) that we have studied for many years."

HSP, a rare disorder that affects about 20,000 people in the U.S., is marked by numbness and weakness in the legs and feet due to progressive deterioration of the longest cells in the body—the neurons that connect the spine to the lower legs.

In 2016 Stern, McNew and colleagues used hundreds of experiments on dozens of mutant strains of fruit flies to show how an HSP gene produced defective synapses at the junctions between nerve and muscle cells. In follow-up work last year, McNew, Stern and postdoctoral researcher Shiyu Xu conducted more experiments to see exactly how these synapse defects caused neurons to malfunction and die.

"Shiyu wasn't able to find any evidence of neurodegeneration, but he did find evidence of muscle degeneration," Stern said. "That was a surprise, and we didn't know what to make of it at first. Even though nerve damage is a known cause of muscle atrophy, conventional wisdom is that the nerve cells die first."

Intrigued, the group conducted experiments to see what was happening at the molecular level. Tests suggested elevated TOR activity in the degenerating muscle cells. TOR is short for "target of rapamycin"; when TOR was discovered in the early 1990s, researchers only knew it was the target of a natural compound called rapamycin, an immunosuppressant that had been widely prescribed for decades to transplant recipients.

"We were convinced it was TOR after Shiyu showed he could slow down the muscle degeneration by giving the flies rapamycin," Stern said.

At a healthy synapse (top), neuron-muscle communication (thick green arrow) prevents TOR activation in muscle, permitting repair of cellular structures and muscle survival. Synapse defects (bottom) from HSP mutations and other neuronal disorders disrupt this communication (thin green arrow), which activates TOR protein in the muscle, allowing junk proteins to build up and cause muscle degeneration and ultimately death. Credit: James McNew/Rice University

TOR is an important master regulator of growth and nutrient-sensing. When fully activated, TOR promotes growth so aggressively that cells forgo daily chores such as repairing structural damage and recycling partially functional organelles. In times of extreme stress or starvation, TOR is fully deactivated so the cell can enter a survival mode and conserve scarce resources.

"TOR isn't an on-off switch as much as a knob for dialing growth up or down," McNew said. "It's not that high TOR is bad and low TOR is good. Each is needed under certain conditions, and TOR's function—which is essential in all higher-order life, from yeast to humans—is to modulate growth to match the conditions it's detecting."

Stern said, "What appears to be happening in the muscle cells that aren't receiving neuronal signals is that the knob gets switched onto high and stays there. TOR locks the cells into this aggressive, pro-growth mode and they stop cleaning up all of the reactive oxygen species, or free radicals, which gradually build up and cause such high levels of stress that the cell dies."

Stern said this hypothesis jibes with observations from numerous other studies that have found high TOR levels and high levels of oxidative stress in the brain cells of patients with Alzheimer's as well as the atrophied muscles of patients who are paralyzed or bedridden.

"In muscle atrophy studies in mice, where the motor neuron is cut, they've found that TOR is activated," he said. "This might be mechanistically similar to our case or to what's been seen in Alzheimer's because people have also found activation of the stress pathway that's induced by reactive oxygen species."

Stern said previous studies also have identified some of the molecular players involved in the degeneration domino effect—including two proteins known as the JNK kinase and the FOXO transcription factor—but he and McNew are the first to connect the dots between TOR and the stress-pathway proteins.

"We also see FOXO activation in our degeneration model, but we know—or at least we think we know—what is activating FOXO," Stern said. "We hypothesize that TOR causes a buildup of reactive oxygen species that in turn activates a molecule called JNK, which activates FOXO."

McNew said focusing on the damage from overactive TOR means that any clues he and Stern find could potentially apply to any disease or condition in which TOR activation is implicated.

"The things that cause TOR to get turned on in a neuron are probably very different than those that turn it on in a liver cell or a white blood cell," he said. "We're focused on the downstream part because once you get TOR turned on, we think it does a handful of things we understand and can directly test. And those are likely to be uniform across different cell types and different conditions. That means anything we find could inform not only HSP pathology but also cancer and neurodegenerative diseases like Alzheimer's and Parkinson's."

Provided by: Rice University

https://medicalxpress.com/news/2018-06-biochemists-clues-alzheimer-cancer-longevity.html

How the office org chart in your brain helps to organize your actions

June 28, 2018, Salk Institute

A long-term debate in behavioral neuroscience is whether behavior is organized in a hierarchy or as a chain. This diagram shows how a sequence of left (L) and right (R) actions performed by mice in the current study would be organized under each theory. Credit: Salk Institute

Driving to work, typing an email or playing a round of golf—people perform actions such as these throughout the day. But neuroscientists are still unsure how the brain orchestrates complex actions or switches to a new action—behaviors that are impaired in disorders such as Parkinson's disease or obsessive-compulsive disorder (OCD).

Now, Salk researchers have resolved a longstanding scientific debate about how behavior is organized in the brain. Led by Associate Professor Xin Jin, the team discovered that learned behavior is organized in a hierarchy with multiple levels of control, offering possible new therapeutic targets for disorders that involve an inability to control one's actions. The work, which appeared in the journal Cell on June 28, 2018, utilized mice trained to perform complex action sequences to make the discovery.

"For many decades, scientists have been debating how the brain organizes behavior," says Jin, the study's senior author. "Using optogenetics, a technique that uses light to manipulate brain cells' activity, we were able to change individual actions that the animals were planning to perform, revealing this precise level of neural control."

When you learn a new behavior—such as tying your shoelaces—a brain region called the striatum orchestrates the series of actions: bending down, grabbing the laces, and tying the knot. Scientists have long debated whether these types of steps are organized in a chain, with each step triggering the next (like falling dominoes) or whether there is a more hierarchical system at work, with multiple levels of control (like an office organization chart).

Over several weeks, Jin's team trained mice to carry out a series of lever presses. In a custom-built box with a lever to the left and a lever to the right, the mice learned that pressing the levers in the specific order of left-left-right-right yielded a treat. (The team named this series "the penguin dance" after a line dance sometimes performed at weddings or parties.)

While the mice performed the penguin dance sequence, a computer recorded the activity of two specific types of brain cells: D1 and D2 neurons, which make up the majority of cells in the striatum and have been implicated in learning and performing actions. The researchers used optogenetics to activate these neurons with laser light and diphtheria toxin to inactivate them, allowing the team to identify and isolate how D1 and D2 cells control behavior.

Interestingly, stimulating D1 neurons caused the mice to add one additional lever press to the sequence, while stimulating D2 neurons caused the mice to skip the next lever presses.

By manipulating D1 or D2 neurons at precise points during performance of the penguin dance, the researchers were able to piece together how the sequence was learned and organized by the brain. They also discovered unexpected mixtures of the neurons working in tandem to drive or suppress behavior.

"Neurons are like snowflakes," says UC San Diego graduate student and Salk researcher Claire Geddes, the paper's first author. "D1 and D2 neurons have certain similar patterns, but they don't all do exactly the same thing. There's a complexity to how they work together to control movement."

The researchers from left: Xin Jin and Claire Geddes. Credit: Salk Institute

The team found evidence for three levels of control in neuronal activity. The lowest level represented activity with each individual step in the action sequence, while the highest level represented activity only when starting or stopping the overall sequence. At an intermediate level, neurons were active only during the animals' switch from one action to another. It's akin to an employee's supervisor overseeing every task versus a senior executive who mostly monitors whether a project was begun or completed. In between are the organization's middle managers, operating amid the other two.

According to Jin, Geddes and coauthor Hao Li, the work reveals a subtle complexity to neuronal behavior in the striatum that may help explain why the learned actions we perform remain so flexible—our brain's supervisors, middle managers and senior executives can update our behaviors to respond to challenges in our ever-changing environment.

Adds Jin, "I'm particularly excited about this study because it solves a long-standing debate for a fundamental question in behavioral neuroscience. At the same time, by identifying how different cell types in the brain control our behavior, it provides new insight into potential treatments for different neurological diseases."

Journal reference: Cell 

Provided by: Salk Institute 

To see video:

https://medicalxpress.com/news/2018-06-office-org-brain-actions.html

Sounds of moving objects change perceptions of body size

June 27, 2018, University College London

Sound and object motion can be used to change perceptions about body size, according to a new study by an international team involving UCL researchers.

The study, published today in PLOS ONE, found that introducing a mismatch between the predicted and actual outcome of an action, such as dropping a ball, can make people feel taller.

When an object is dropped, the brain accurately predicts when it will hit the floor by considering the height from which it fell. Artificially lengthening the time it takes to hear the impact of the object on the ground leads people to update their perceived body height, making them feel taller.

How humans perceive their body size is highly flexible, even beyond the ages when we stop growing. Most previous studies into this used sensory feedback on or about one's body but this study shows that even objects around us are used to compute our body size.

The findings could have implications for studies already using sound for rehabilitation for people with poor proprioception—the sense of the position of parts of the body in relation to other parts—including for those who have Parkinson's Disease or have suffered a stroke.

"These results reveal the surprising importance that sound and movement have on body representation. We don't just feel and see our bodies, we also hear ourselves whenever we interact with solid objects," explained lead researcher Dr. Ana Tajadura-Jiménez (UCL Interaction Centre and Universidad Carlos III de Madrid).

"This could be a really promising avenue for treating clinical conditions where people suffer from chronic pain or other conditions linked to distorted mental body representations such as anorexia nervosa."

"As these mechanisms are understood, they inform the design of sound-based technology to support novel therapies for such conditions," added co-author Professor Nadia Berthouze (UCL Interaction Centre and UCL Psychology & Language Sciences).

For the study, blind-folded participants dropped a ball from head height. The actual sound of the ball dropping and hitting the floor was masked and a simulated sound was played at longer and shorter intervals using four simulations—actual height, or from half, two or three times this height.

Participants were then asked to take a step backwards to an already memorised point and visually estimate their body size. "Results show that as the perceived time it took the ball to hit the floor increased, so too did the participants' perception of their body height and leg length", explained co-author Prof Ophelia Deroy (LMU).

Co-author Dr. Norimichi Kitagawa (NTT) added: "This is not only valuable for clinical applications but could also inform the development of technologies for motion controlled games where players take on a larger character on screen."

More information: Audio-tactile cues from an object's fall change estimates of one's body height, PLOS ONE (2018). journals.plos.org/plosone/arti … journal.pone.0199354

Journal reference: PLoS ONE

Provided by: University College London

https://medicalxpress.com/news/2018-06-perceptions-body-size.html

My father received poor treatment for Parkinson's. Here's what I did

Neil Archibald     

Thu 28 Jun 2018

His care left me horrified – but it spurred me on in my medical career to make sure others didn’t face the same ordeal

For much of the time while my dad had Parkinson’s I was a neurology trainee.’ Photograph: Alamy Stock Photo

As tremors go, it wouldn’t have rated much on the Richter scale but, back in 1990, the shake in my father’s right hand had a seismic impact on him, and our family.

Dad was in his late 50s, a research chemist, and was hoping to retire in a few years. I was a nerdy 16-year-old Belfast schoolboy, with aspirations of medical school. I can still recall the day he came back from the hospital appointment that confirmed all our fears – it was Parkinson’s.

For the first few years, things seemed to be OK. Dad was taking medication that was working – he was able to get about, do what he wanted and his intellect and wit still shone through. It was only when I started working as a junior doctor that things got more difficult.

There was no eye contact with the doctor, no empathy and our concerns about my father's deterioration were brushed aside

Dad’s response to his treatment had become increasingly unpredictable. He would be stuck to the spot like a mannequin, waiting what felt like hours for his medication to kick in. Once it did, he was great again, but the tablets would wear off far more quickly. Our days became ruled by the clock – hoping he would make it through to his next dose without the last one completely wearing off. 

Hoping for an improvement, I accompanied him to one of his neurology appointments, trying hard not to be the annoying medical relative in the consultation. We couldn’t have been in there more than five minutes before we were out of the door again. There was no eye contact, no empathy and our concerns about his deterioration were brushed aside with, “Of course he’s progressed, it’s an incurable, progressive condition”. I was horrified and angry. This was not how it was supposed to be done.

Things went from bad to worse, but there was nowhere to turn for advice or support – the services just did not exist. Dad was frustrated and, at times, anxious. Then disaster struck when he slipped on the stairs and broke his hip. Pain, hospitalisation, a major operation, sepsis and strong painkillers all took their toll. The father I knew, the one who went into hospital that night, never really came out again.

Dad had developed Parkinson’s disease dementia. Hallucinations and confusion became the norm, with mum becoming carer and comforter, in addition to loving wife. My brother, sister and I all did shifts, sometimes overnight. There were glimpses of the old dad, even then – his love of sport, his love of being in the company of family – but these windows of lucidity grew shorter and, little by little, month by month, we lost him. 

As his condition became more complex, the hospital seemed to take less interest. The appointments remained infrequent, brief and unhelpful. There was no specialist Parkinson’s nurse to speak to, no support or advice for my mum. There was no physiotherapy and nobody seemed to know what to do about the hallucinations, the confusion, the anxiety, the falls. The help we did get was disjointed and every day felt like a huge battle.

For much of this time I was a neurology trainee. I completed a PhD on hallucinations in Parkinson’s and, in 2012, finally became a consultant neurologist, with a specialist interest in Parkinson’s. Dad got to see me reach that milestone, but only just. He died five years ago and, looking back, I can see just how much he, and his illness, has shaped me. I have his scientific brain, his odd sense of humour and, sadly, his nose, but I also have the legacy of his Parkinson’s. I’ve had the kind of education no son ever wants, but every neurologist needs. I’ve seen complex Parkinson’s first hand and I know the impact it has. I’ve seen how a service can let a patient and their family down and I’ve learned the hard way why things need to be done differently. 

I decided that my patients shouldn’t have to experience the same issues that we faced with my father, and I set up the Parkinson’s advanced symptoms unit (Pasu) in Teesside. We see people with this complex condition quickly, and support them with a passionate, highly skilled team of Parkinson’s specialists – nurses and doctors, but also mental health workers and therapists. It’s a service I’m incredibly proud of; one that is making a massive difference in our region. It’s also a service I know is almost entirely inspired by my father.

If you would like to contribute to our Blood, sweat and tears series about experiences in healthcare, read our guidelines and get in touch by emailing sarah.johnson@theguardian.com

https://www.theguardian.com/healthcare-network/2018/jun/28/father-received-poor-treatment-parkinsons-heres-what-did

FoxFeed Blog: Ask the PhD: Spring 2018 Funded Parkinson's Projects

Posted by Maggie McGuire Kuhl,     June 27, 2018

https://youtu.be/BvORTKmUdYc

The Michael J. Fox Foundation (MJFF) announces $7.7 million in new funding for 39 projects chosen through our biannual call for applications. I sat with MJFF Senior Vice President of Research Programs Mark Frasier, PhD, to explore some of these innovative studies. Highlights include retinal scanning for diagnosis, an asthma drug for Parkinson's, and tracking the cellular effects of pesticide exposure.

This is the first in our new video series "Ask the PhD," a complement to our popular "Ask the MD" series. While "Ask the MD" focuses on aspects of Parkinson's disease and care, this new series will offer the latest from the MJFF research portfolio and new findings that advance understanding, measurement and treatment of Parkinson's.

Read our press release on the 39 new funded projects from our spring 2018 funding round at: 

https://www.michaeljfox.org/foundation/publication-detail.html?id=662&category=7

https://www.michaeljfox.org/foundation/news-detail.php?ask-the-phd-spring-2018-funded-parkinson-projects

British Crew Rowing the Distance to Improve Understanding of Parkinson’s Disease

JUNE 27, 2018 BY CAROLINA HENRIQUES 

A four-man crew from Britain is hoping to increase understanding of Parkinson’s diseaseby rowing across the Indian Ocean in an attempt to break a world record.

Robin Buttery, Barry Hayes, James Plumley, and skipper Billy Taylor are planning to row for 1,920 hours non-stop, for 65 days straight, all the way from West Australia to Mauritius, with the goal of becoming the fastest four-man crew to row the Indian Ocean.

The effort is an attempt to raise awareness of the disease and raise funds to support research — all while serving as subjects of scientific research aimed at studying the relationship between physical exercise and Parkinson’s.

Buttery, 46, was diagnosed with young-onset Parkinson’s disease two years ago, just before his 44th birthday. He lives in Leicester with his wife, Nicola, and son Rory, and works as a technical instructor at De Montfort University in Leicester.

Determined to show that life does not end with a Parkinson’s diagnosis, he challenged three friends to join him in his attempt to break a world record and serve as an inspiration to the community. The crew members will row non-stop, taking shifts of two hours on, two hours off, for 12 weeks.

They will start their journey in Exmouth, Western Australia, and row 3,600 nautical miles in a 29-foot-long ocean rowing boat until they reach their destination in Port Louis, Mauritius.

Cameras on the boat will film the crew 24/7, gathering footage that will be processed by computers after the journey is complete. Researchers will then analyze the video to study the effects of exercise on Parkinson’s.

Although physicians often prescribe physical exercise for Parkinson’s patients and anecdotal evidence shows that common motor symptoms such as tremors, cramps, and gait issues are improved with exercise, very little is really known about how exactly physical activity affects Parkinson’s patients.

By studying Buttery and his crew mates, professors Helen Dawes, Fabio Cuzzolin, and Johnny Collett of Oxford Brookes University in the U.K. hope to answer questions such as whether endurance exercise is always better than other types of exercise and if endurance exercise affects Parkinson’s patients differently than non-patients.

They will compare the changes in Buttery’s movements with those of his crew mates to investigate how endurance exercise affects the motor skills of Parkinson’s disease patients. They can also enlarge the video to look at any changes in their heart and lung regulation.

By analyzing the progression of Buttery’s motor skills and other Parkinson’s symptoms while exercising, the researchers hope to learn more about how physical activity really affects this disease.

Other researchers will also use this venture as a case study. Oxford Brookes research fellow Shelly Coe, a qualified nutritionist, for example, will monitor how diet impacts the management of Buttery’s symptoms.

All of the information these researchers gather could potentially help with the development of new treatments for Parkinson’s disease.

In addition to serving as subjects of scientific observations and attempting to break a world record, the team is also raising funds for charity. They are hoping to raise a minimum of $350,000 to support the Restoration of Appearance and Function Trust, Clear Trust and the European Parkinson’s Disease Association.

Anyone can support the crew and their goal by buying a mile or by making a donation. Once they depart, a livestream of their journey will be available on their website at:   http://www.rowtheindianocean.com

https://parkinsonsnewstoday.com/2018/06/27/british-crew-plans-row-indian-ocean-increase-parkinsons-understanding/

Combating the Fear of Living with Parkinson's Disease

June 27, 2018   BY "SHERRI WOODBRIDGE"

There is an acrostic I have seen for “fear”:

False

Evidence

Appearing

Real

I am sure the author of that acrostic meant well, and while there is some validity to it, it is not completely accurate. Ask anyone who is dealing with any kind of illness. Speak to an elderly person who knows they only have days, maybe weeks left to live. A mother who is waiting to see if the test results of the baby she carries are accurate. The father who just lost his young wife and must now raise his three young children on his own. Or the single mother who has just lost her job.

These people’s fears don’t just appear real. They are real. Those who live with a chronic illness deal with fear daily. A chronic disease robs you of the joy in your journey, the delight in your day. It steals your contentment and calm, replaces wonder with worry. So what do you do when the worry ogre comes to call? When fear capsizes its ship in your harbor and leaves you to deal with the wreckage? How do you handle the kind of fear that does that?

In his book, “Fearless,” Max Lucado examines fears relating to finances, children, violence, and more. However, he doesn’t address the fears of living with a chronic illness. Yet, tackling the fear of unemployment, our children’s safety, violence, chronic illness, etc., are all dealt with in the same way.

Fear is a feeling or emotion about a perceived threat, either real or imagined. It’s the condition of being afraid. It is having a feeling of dread and hopelessness. It is assuming something terrible is going to come out of a given situation. Having Parkinson’s disease can make you feel like that: afraid, threatened, hopeless.

We fear losing our ability to talk coherently. To sing or dance. To write, read, paint, draw. We fear losing the ability to hold our children or grandchildren, to hug our spouse. We fear having to depend on others for help with everyday tasks. We fear there will be no cure. We fear we will be left to die with this cruel disease instead of the more abstract fear of being hit by an unmanned, runaway ice cream truck.

Fear implies a sense of anxiety and a loss of courage. With fear, there is an intense reluctance to face or meet a specific situation such as Parkinson’s disease. There is an aversion to fear, and rightly so.

One thing I don’t want to be in this battle against Parkinson’s disease is a coward, but it’s certainly easy to let the fears take control and to think about the “what ifs.” This is when I step back and ask myself where my faith lies.

A friend, Ardyce Glessing, shared the following in a Facebook group: “I too have fears of not being able to look after myself and be dependent on my family for everything. I am used to taking care of everyone else and I wish it could stay that way. Somedays I do pretty good and try to carry on and think positive, but at times I just break down and cry from, I guess, a fear of the unknown. Eventually, I get over it and carry on with the rest of my day. I can honestly say it’s always in the back of my mind though. My family is supportive, but I don’t like to continually complain about my problems so just usually say ‘I’m doing good”. Every day I pray for a cure or a medication that stops the progression of PD.”

A recurring theme in facing and combatting fears seems to be having a positive attitude. Although this may seem basic, it’s often hard to muster up courage when you’re facing your little monster every day. I like Ardyce’s fear-buster tip: “Have a good cry.”

There is a legitimate fear in not knowing what the future holds, but thankfully, I believe God holds the future. So, while we can have a good cry now and then, we can also remember God still remains in control, even though all around us it seems life is unraveling.

I think we all have fears, but we seldom talk about those fears. I find myself moving onto other things to distract myself from harmful thoughts that may never amount to anything.

And again, Ardyce is spot on: Sometimes we just need a good cry to wash those fears away.

***

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.

https://parkinsonsnewstoday.com/2018/06/27/parkinsons-disease-conquering-managing-fear/

Drug protects neurons in Parkinson's disease

June 27, 2018 by Will Doss, Northwestern University

Systemic treatment of animal models with israpidine, a calcium channel inhibitor, reduced mitochondrial stress that might cause Parkinson's disease, according to a Northwestern Medicine study published in the Journal of Clinical Investigation.

These findings bode well for the STEADY-PD III study, a nationwide clinical trial testing isradipine in patients at Northwestern and over 50 other sites across the United States, according to D. James Surmeier, Ph.D., chair and Nathan Smith Davis Professor of Physiology, and senior author of the study

"Obviously, humans are more complicated than mice, but we're hopeful the trial will be positive," Surmeier said.

Isradipine has recently emerged as a potential treatment for early-stage Parkinson's disease, according to Surmeier. While it was originally intended to treat high blood pressure to reduce the risk of heart attack or stroke, patients who took this drug to treat hypertension also had lower rates of Parkinson's disease—putting it on the map for neurologists and neuroscientists.

Scientists investigating this phenomenon hypothesized that the lower disease rates may have been caused by isradipine's neuroprotective effects on dopaminergic neurons, the death of which is a large contributor to Parkinson's disease symptoms.

Running Hot

Dopaminergic neurons are critical to mobilizing regions of the brain that allow rapid movement in response to events. As a consequence, those neurons are always on "high alert." To ensure that they have the energy necessary to play this sentinel role, dopaminergic neurons keep their mitochondrial power-plants running at nearly full capacity, Surmeier said.

"They tune up cellular respiration so that no matter what kind of demand or unexpected excitation comes their way, they can continue to do their job," Surmeier said.

While it's useful in fight-or-flight situations, running "hot" for so long can produce toxic compounds that eventually kill the neurons, as seen in Parkinson's disease.

"Humans, in general, are not confronted with this kind of demand anymore," Surmeier said. "In our distant past, we had unexpected dangers all around and we had to be ready to escape or attack if we were to survive—that's not the situation anymore, particularly if you're 50 years old."

In experiments, isradipine inhibits calcium channels that stimulate mitochondria. By inhibiting these channels, mitochondrial respiration slows and their production of damaging compounds drops.

However, it was unclear if giving israpidine to live mice through the circulatory system would achieve the same effect—particularly when administered over a long period of time and at doses that are tolerated by humans.

From Mice to Men

In the current study, the scientists treated adult mice with isradipine for over a week and then measured the calcium levels in dopaminergic neurons using two-photon laser scanning microscopy—one of the first studies to use quantitative imaging to measure calcium levels inside cells, according to Surmeier.

They found that calcium levels in dopaminergic neurons were lowered after treatment, demonstrating the calcium channels were being inhibited in live models. In addition, this showed a drug didn't lead to an up-regulation of calcium channels that would undermine the goal of treatment, Surmeier explained.

"Often when you perturb cells, they'll compensate—if you knock out a protein, another protein with a similar function is up-regulated to compensate," Surmeier said. "When the the gene for the channel that controls mitochondria was knocked out early in development of dopaminergic neurons, the neurons up-regulated the expression of another channel that filled in for the lost channel."

In addition, the study found the mitochondria of dopaminergic neurons treated with isradipine had lower oxidant stress than in untreated neurons.

Using a genetically encoded probe to measure mitochondrial turnover, they found that the high oxidant stress in dopaminergic neurons caused mitochondrial damage, forcing the neurons to replace these key organelles more frequently than in other healthy neurons. However, by lowering mitochondrial stress, isradipine diminished the damage to mitochondria and reduced turnover.

"We diminished the damage being done to mitochondria enough that dopaminergic neurons looked the same as neurons that are not lost in Parkinson's disease," Surmeier said.

Further, there were no serious side-effects and the animals' behavior was normal, indicating the therapy may work in human patients. However, that question won't be answered until the results of the STEADY-PD III trial are available in the spring of 2019.

Tanya Simuni, MD, chief of Movement Disorders in the Ken & Ruth Davee Department of Neurology and Arthur C. Nielsen, Jr., Research Professor of Parkinson's Disease and Movement Disorders, is the primary investigator of the multicenter study funded by the National Institute of Neurological Disorders and Stroke.

"These data provide additional strong pre-clinical rational for the ongoing phase III study of israpidine in human patients," Simuni said. "We are cautious as so many drugs have failed, but if successful, isradipine will be the first drug to demonstrate the ability to slow progression of Parkinson's disease."

However, it's unlikely any single Parkinson's disease therapy will be a magic bullet—instead, Surmeier views isradipine as part of a multi-faceted therapy, with components targeting different elements of the disease mechanism.

"If you can partially inhibit a few different links in the disease chain, the net effect is very large, but the side-effect profile is manageable," Surmeier said. "We're hopeful isradipine works, but it's likely an optimal therapy will be one that targets a few elements."

More information: Jaime N. Guzman et al. Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI95898

https://medicalxpress.com/news/2018-06-drug-neurons-parkinson-disease.html