New Scanner Worn as Helmet Allows Brain Imaging in Parkinson’s Patients

MARCH 27, 2018      BY PATRICIA INACIO, PHD 

A new brain scanner that can be worn as a helmet could potentially revolutionize the world of human brain imaging, allowing patients with Parkinson’s disease to undergo brain scanning — a task previous traditional scanners failed.

Brain cells use electrical impulses to communicate and, in doing so, form small magnetic fields that can be detected outside the head. Human brain function can be imaged by capturing these magnetic fields through a technique called magnetoencephalography (MEG).

With current scanners, patients have to remain perfectly still while being scanned, as even a tiny movement could render the images unusable. This means it is very difficult to scan people who find it hard to remain still, such as patients with movement disorders.

Researchers at the Sir Peter Mansfield Imaging Centre, University of Nottingham UK have tackled this issue by developing a new MEG system that’s worn as a helmet, allowing subjects to move around freely and naturally during scanning.

The new scanner is more sensitive than current systems, giving a detailed, millisecond-by-millisecond picture of the brain while subjects perform different tasks, such as speaking or moving.

It was recently described in the study, “Moving magnetoencephalography towards real-world applications with a wearable system,” published in the journal Nature.

“This new technology raises exciting new opportunities for a new generation of functional brain imaging. Being able to scan individuals whilst they move around offers new possibilities, for example to measure brain function during real world tasks, or genuine social interactions. This has significant potential for impact on our understanding of not only healthy brain function but also on a range of neurological, neurodegenerative and mental health conditions,” Matt Brookes, PhD, the study’s co-lead author, said in a press release.

Traditional scanners are extremely heavy, weighing about half a ton, because their sensors require extremely low temperatures (-269 degrees Celsius, equivalent to -452 degrees Fahrenheit), which means the machine must contain built-in cooling technology.

The new scanner has scaled-down technology that takes advantage of “quantum” sensors incorporated in a 3-D printed prototype helmet. The new sensors are extremely lightweight and can work at room temperature, allowing them to be placed directly onto the patient’s head. This positioning also means the sensors are closer to the brain, increasing the amount of signal they can pick up.

To allow patients to move their heads during scanning, researchers had to adjust the helmet’s electromagnetic potential and build special electromagnetic coils.

After designing a successful prototype, researchers are now developing new types of helmets to fit babies and children, as well as adults. They predict this new type of scanner will increase the sensitivity of brain imaging fourfold in adults, and up to 15 or 20 times in children.

“This has the potential to revolutionize the brain imaging field, and transform the scientific and clinical questions that can be addressed with human brain imaging. Our scanner can be worn on the head like a helmet, meaning people can undertake tasks whilst moving freely. Importantly, we will now be able to study brain function in many people who, up until now, have been extremely difficult to scan — including young children and patients with movement disorders. This will help us better understand healthy brain development in children, as well as the management of neurological and mental health disorders,” said Gareth Barnes, PhD, a professor and the leader of the project at Wellcome Centre for Human Neuroimaging at University College London.

https://parkinsonsnewstoday.com/2018/03/27/new-wearable-scanner-allows-brain-imaging-parkinsons-patients/

Increased risk of overactive bladder in patients with idiopathic Parkinson's disease: Insight from a nationwide population-based cohort study.

 March 25, 2018

Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder characterized by typical motor impairment. However, lower urinary tract symptoms, including urinary urgency or frequency, which are non-motor phenomena, occur frequently among patients with IPD. In this study, we assess the risk of overactive bladder (OAB) in patients with IPD.

The National Health Insurance Research Database of Taiwan was used to identify patients with IPD (IPD cohort) and four-fold controls (non-IPD cohort) from 2000 to 2010. The non-IPD cohort was matched according to age, sex, and baseline comorbidities, including benign prostate hyperplasia, stress incontinence, diabetes, and cerebrovascular diseases. The occurrence of OAB was monitored until the end of 2011. Hazard ratios of OAB were estimated using Cox proportional hazards regression models.

In total, 4,571 and 18,255 patients were included in IPD and non-IPD cohorts, respectively. Results showed a significantly higher overall incidence rate of OAB in the IPD cohort compared with the non-IPD cohort (14.5 vs. 6.37 per 10,000 person-years), with a 2.3-fold increased risk of OAB (95% confidence interval [CI] = 1.51-3.51) after controlling for benign prostate hyperplasia and stress incontinence. The mean follow-up period for the IPD cohort was 5.0 years. This cohort study showed that the cumulative incidence of OAB was 0.65% at the fifth year and 1.54% at the tenth year after IPD diagnosis; this risk was highest in the age group 65-74 years.

This study reveals that IPD is independently associated with an increased risk of OAB in patients with IPD. The probability of OAB was 1.54% over a 10-year period after IPD diagnosis; the risk of OAB is considered to be age-dependent and most substantial in patients aged 65-74 years.

PloS one. 2018 Mar 02*** epublish ***

Fu-Yu Lin, Yi-Chien Yang, Cheng-Li Lin, Lukas Jyuhn-Hsiarn Lee

Department of Neurology, China Medical University Hospital, China Medical University School of Medicine, Taichung, Taiwan., College of Medicine, China Medical University, Taichung, Taiwan., National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/29499067

https://www.urotoday.com/recent-abstracts/pelvic-health-reconstruction/overactive-bladder/103082-increased-risk-of-overactive-bladder-in-patients-with-idiopathic-parkinson-s-disease-insight-from-a-nationwide-population-based-cohort-study.html

FoxFeed Blog: Snow Doesn't Stop Advocates from Making an Impact in Washington

Posted by  Allyse Falce, March 26, 2018

Last week, 300 Parkinson's disease (PD) advocates from nearly all 50 states convened in Washington, D.C. for the 2018 Parkinson's Policy Forum. This annual event brings people with PD and their loved ones to our nation's capital for two days of education and training followed by a day of advocacy action and engagement. Despite a snowstorm that closed Congress' doors and shut down the streets of Washington, advocates made sure the Parkinson's community was heard on Capitol Hill.

This year's Forum was co-sponsored by the Parkinson's Foundation and The Michael J. Fox Foundation (MJFF). Nine other PD organizations also contributed time and resources to help make the event possible.

"When Parkinson's groups come together to advocate for change, we amplify our message and have a greater chance of influencing public policy," says John Lehr, CEO of the Parkinson's Foundation. "This collaborative approach is key, and we look forward to working together in this way long after the Forum is over."

The event began with two days of educational panels where advocates learned about recent research advances and current policy issues affecting people with Parkinson's, their families and care partners. Attendees also received training on how to build relationships with lawmakers and be an effective advocate. Six sessions were streamed live on Facebook and have already garnered nearly 59,000 total views.

Senator Cory Booker, whose late father lived with Parkinson's, delivered a keynote speech on the morning of Tuesday, March 20. "I tell each and everyone one of you, what you do matters," he said, underscoring the importance of advocacy. (View the senator's full remarks.)

On the final day of the event, advocates were scheduled to head to Capitol Hill for congressional meetings but the government shut down due to a snowstorm. Attendees, determined to make their voices heard, rallied and spent the day calling and emailing each of their senators and representatives to ask for increased Parkinson's research funding in Fiscal Year (FY) 2019. (Congress just passed the FY 2018 spending deal, including a $3 billion boost for the National Institutes of Health, and is now negotiating funding for FY 2019). Advocates also recorded short videos on this topic and posted them to their legislators' social media feeds. (Search for the hashtag #act4PD on Twitter to see our community in action!)

"I couldn't see my members of Congress in Washington, but that's not going to stop me. I know there are many other ways to speak up for the issues that are important to me. I'm already working on setting up meetings with my legislators when they come back to my home state of New Mexico," said advocate Karen St. Clair. "Advocacy is an activity we must engage in all year round, and I'm going to continue to use what I learned at the Forum to educate my elected officials on what matters to people with PD and their families."

At the same time Forum attendees were advocating from their hotel, thousands of people across the country joined these efforts by participating in Parkinson's Advocacy Day. PD community members sent an impressive 14,000 emails to their lawmakers on this day of action, emphasizing the importance of robust federal research funding. These emails reached all 100 U.S. senators and nearly all 435 members of the House of Representatives. 

"While the government was closed, some congressional phone lines were open. The staffers who answered our calls told us that they were hearing from many people with PD," says Ted Thompson, JD, senior vice president of public policy at MJFF. "Our voices are getting through, and Congress is taking note of our needs and priorities. We couldn't be on Capitol Hill in person, but there's no doubt in my mind that we made an impact in Washington."

https://www.michaeljfox.org/foundation/news-detail.php?snow-doesn-stop-advocates-from-making-an-impact-in-washington

Franklin County Auditor details health battle with Parkinson's disease

by Stacia Naquin 

Monday, March 26th 2018

COLUMBUS, Ohio — No mission too difficult. No sacrifice too great. Duty first.

That’s the motto of the Army’s 1st Infantry Division and it stays with Franklin County Auditor Clarence Mingo, who served with the 1st ID.

It’s a motto he calls on now, as he faces a different kind of battle. But it’s one you may not see, as Mingo offers a smile and handshake for everyone he meets, especially at the Chalmers P. Wylie VA Ambulatory Care Center. For Mingo, this is where his walk with health challenges began in 1993, after returning from the Persian Gulf.

“I was among those veterans who came back with a range if un-diagnosable symptoms – all of them neurological,” said Clarence Mingo, Franklin County Auditor. “Over time, those symptoms sort of morphed into what most people call Parkinson’s Disease or Parkinson-ism.”

According to the Mayo Clinic, Parkinson’s Disease is a progressive disorder of the nervous system that affects movement and develops gradually, changing even the simplest tasks.

“Every day, it’s hard to get up,” said Mingo. “It’s hard to get dressed. It’s hard to groom myself and do all the things that a normal person would do in good order and with deliberate speed. But what I learned in the army … that can-do mentality that idea that it may take me a little longer, but I’ll work harder and we’ll get through it. I still live with that.”

Officially diagnosed in 2013, Parkinson’s may have changed his life. But it hasn’t slowed him down.

“I want to walk with Parkinson’s,” said Mingo. “I want to walk with it… not merely live with it, but walk with it and in a positive and healthy way.”

There is no cure for Parkinson’s Disease, but many symptoms can be managed with medication and other treatments. Auditor Mingo calls himself a “frequent flyer” at the VA over the last 5 years, receiving primary care, physical therapy, and occupational therapy.

He continues to stay busy with family and his many responsibilities as the Franklin County Auditor – working with the community on property values, taxes, and licenses for pets.

Each day offers him a new opportunity to share the message about the impact of Parkinson’s Disease. It’s an impact that goes far beyond the physical symptoms.

“A lot of times we look at the weaknesses in our lives and we think those weaknesses are reasons why we can’t and other people will tell you that too,” said Mingo. “But I’ve learned because of this disease that weaknesses can very much be strengths.”

Auditor Mingo says Parkinson’s Disease has given him a chronic purpose – to engage, be active and contribute.

So, even when the days get tough, he calls on those familiar words from the Army’s 1st Infantry Division.

“No mission too difficult. No sacrifice too great. Duty first,” said Mingo, reciting the motto of the 1st ID.

And he continues his walk with Parkinson’s Disease.

“There’s life with Parkinson’s Disease,” said Mingo. “Like everyone else… highs and lows. Still life and, for me, one I’m very thankful to have.”

April marks Parkinson’s Disease Awareness Month.

Video:

http://abc6onyourside.com/news/local/franklin-county-auditor-details-health-battle-with-parkinsons-disease

http://abc6onyourside.com/news/local/franklin-county-auditor-details-health-battle-with-parkinsons-disease

Mutation Can Trigger Parkinson’s Outside the Brain, Study Finds

MARCH 26, 2018   BY JOSE MARQUES LOPES, PHD 

The most common gene mutation in Parkinson’s triggers disease outside the brain by changing the body’s immune response to common infections, a study in mice reports.

The research, “Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo,” was published in the journal Brain.

Parkinson’s patients typically lose dopamine nerve cells in a brain area called substantia nigra, resulting in protein clumps known as Lewy bodies and an increase in brain inflammatory cells. In fact, increasing evidence shows that nerve cell inflammation is key to the development of the disease.

“We know that brain cells called microglia cause the inflammation that ultimately destroys the area of the brain responsible for movement in Parkinson’s,” Dr. Richard J. Smeyne, the study’s senior author, said in a press release. “But it wasn’t clear how a common inherited mutation was involved in that process, and whether the mutation altered microglia.”

Only 10 percent of Parkinson’s cases have a genetic cause. Among these, LRRK2 gene cause the most cases. Mutated LRRK2 is found in 15 to 20 percent of Parkinson’s patients who are Ashkenazi Jews patients and in 40 percent of patients who are North African Arab Berbers.

But the precise link between LRRK2 and Parkinson’s remains poorly understood.

“We know that gene mutation is not enough to cause the disease,” said Dr. Elena Kozina, the study’s first author. “We know that twins who both carry the mutation won’t both necessarily develop Parkinson’s.” Another “initiating event,” or hit, is needed, she said.

Smeyne’s team had already observed that a certain strain of influenza virus predisposed mice to develop disease characteristics that mimic Parkinson’s. This prompted them to wonder if a second hit could come from an infection.

The scientists suspected that LRRK2 mutations could be causing effects outside the brain. To test that idea, they used lipopolysaccharide (LPS) — the major component of the outer shell of gram-negative bacteria — to trigger an immune reaction in the mice.

Neither LPS nor the immune cells it activates are able to cross the blood-brain barrier. This gave the team the perfect tool to test whether inflammation on the periphery affects the brain.

They gave LPS to mice with high levels of the two most common LRRK2 gene mutations. LPS triggered a three to five-fold increase in inflammatory regulators, called cytokines, in these mice, compared with control mice and mice with normal LRRK2.

The cytokines were produced by immune T- and B-cells, two types of white blood cells.

Mice with high levels of cytokines also showed enhanced LRRK2 gene expression in certain immune cells and in activated cells of the brain. This led to nerve cell loss in the substantia nigra, a brain area that plays a critical role in movement.

Nerve cell inflammation in these mice may have been triggered by the ability of circulating cytokines to cross the blood-brain barrier and enter the brain, the team said. This could have created an environment that led to the destruction of the substantia nigra and therefore, movement impairment.

”Overall, this study suggests that peripheral immune signaling plays an unexpected — but important — role in the regulation of neurodegeneration in LRRK2-associated Parkinson’s disease, and provides new targets for interfering with the onset and progression of the disease,” the researchers wrote.

Smeyne cautioned that further research is needed to confirm this link and test it in humans. However, “these findings give us a new way to think about how these mutations could cause Parkinson’s,” he said.

“Although we can’t treat people with immunosuppressants their whole lives to prevent the disease, if this mechanism is confirmed, it’s possible that other interventions could be effective at reducing the chance of developing the disease,” Smeyne added.

https://parkinsonsnewstoday.com/2018/03/26/parkinsons-mutation-may-trigger-the-disease-outside-the-brain/

What Deep Brain Stimulation Can and Can’t Do

MARCH 26, 2018   BY "SHERRI WOODBRIDGE"

We sometimes don’t get all of our facts straight when it comes to pursuing what we want. As Parkinson’s patients, we only want one thing: a cure. Since we know that a cure is being researched but we don’t know when it will come about, we are grateful for anything that comes along in the meantime.

While that “anything” may not cure us, we’re glad for any way that it helps to make the day-to-day reality of living with Parkinson’s disease easier and more comfortable. This includes things like Sinemet (carbidopa levodopa), a medication that serves as a type of replacement for the missing dopamine in our brains. Or Lexapro (escitalopram), one of those wonder drugs that helps keep us on an even keel, knowing that depression can play a large, often hidden role in Parkinson’s disease, more than most realize.

And then there’s deep brain stimulation (DBS). The National Institute of Neurological Disorders and Stroke describes the treatment as follows:

DBS “is a surgical procedure used to treat a variety of disabling neurological symptoms—most commonly the debilitating symptoms of Parkinson’s disease (PD), such as tremor, rigidity, stiffness, slowed movement, and walking problems. At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications.”

It “uses a surgically implanted, battery-operated medical device called a neurostimulator—similar to a heart pacemaker and approximately the size of a stopwatch—to deliver electrical stimulation to targeted areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and PD symptoms.”

DBS has proven to do more than someone with Parkinson’s disease could have hoped for. But sometimes we forget the facts and hope for so much more. We may forget that DBS isn’t a cure as we come away from the surgery. We’re feeling great after our stimulator has been activated. The tremors have ceased or at least eased. We are getting by with lower amounts of medication. We may not be as stiff or rigid. We can move with less struggle and walk with more confidence.

However, perhaps we seem to be feeling slightly more depressed. Perhaps we’re having trouble finding our “words,” and when we do find them, we struggle to get them out. If only one side of our brain was “stimulated,” perhaps we’re now noticing how the disease seems to have progressed to the other side. But perhaps that side just wasn’t as noticeable prior to the surgery because we were distracted while trying to control the more pronounced side.

There may be more controllable symptoms. There may be less. DBS is not a fix-all. You will still have Parkinson’s when you wake up after surgery, but now it may be an even more “invisible” disease. DBS can control the symptoms. It can give you back so much of what you’ve missed. It seemingly works miracles but it isn’t a cure. Exercise is still vital. Proper medication for the symptoms that DBS doesn’t control (such as depression) need to be monitored regularly.

If you are thinking about having deep brain stimulation, talk to others who have been through it. Read about it. Talk to your doctor and ask every question you can think of. Talk to some more people. If you feel it’s right for you and your doctor supports and recommends the procedure, get the prep work done. If all is a go, then set a date.

However, remember that DBS isn’t a replacement for treatment — it is an extension of well-managed treatment that can enhance your life. If your treatment is not well-managed — medications don’t work well, ons and offs are hit-and-miss, dosages haven’t been updated in a while, etc. — then you probably need to get on track there first.

DBS isn’t a cure, no. But it can make you feel and move a whole lot better. However, you need to remember that what works for one person may not work for another. Parkinson’s disease presents itself differently in each individual, and so each person will respond to treatments differently.

***

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/2018/03/26/parkinsons-disease-helped-dbs-not-cure/

Tracking Parkinson's symptoms with phone app could improve treatment

By Allen Cone  |  March 26, 2018 

Researchers say the use of HopkinsPD and mPower by patients with Parkinson's disease could help improve their own treatment and the way doctors overall handle patients with the disease.

Researchers monitored 129 individuals with Parkinson's disease who remotely completed a series of tasks on a smartphone application to track the disease's severity over time. Photo courtesy of University of Rochester Medical Center

Smartphone software and technology can accurately track the severity of the symptoms of Parkinson's disease, leading to better drugs and treatment, according to a study.

Because Parkinson's symptoms fluctuate widely on a daily basis, it makes it difficult to track the progression of the disease and adjust treatment, researchers said.

Data collected by the app, called HopkinsPD on Android and mPower on iPhone, allowed physicians to get an ongoing look at the patient's condition instead of their visits once every several months.

"This study demonstrates that we can create both an objective measure of the progression of Parkinson's and one that provides a richer picture of the daily lived experience of the disease," co-author Dr. Ray Dorsey, a neurologist at the University of Rochester Medical Center, said in a press release.

HopkinsPD, which is available for smartphones that run the Android operating system, was originally developed by Dr. Max Little, an associate professor of Mathematics at Aston University in Britain. The iPhone version of the app, mPower, was later developed and released in 2015 by Little, Dorsey, and Sage Bionetworks.

For the study, published Monday in the Journal of American Medical Association's Neurology, researchers monitored 129 individuals who remotely completed a series of tasks on HopkinsPD.

The tasks measured voice, finger tapping, gait, balance and reaction time. In all, the researchers analyzed 6,148 smartphone activity assessments from the participants.

The smartphone data was analyzed using a machine-learning algorithm to generate a mobile Parkinson disease score on scale of 1-100 with the highest number the greatest severity.

The researchers also conducted in-person visits with 58 individuals with Parkinson's disease and controls in the clinic at URMC. They were asked to complete tasks on the app and were also seen by a neurologist and scored using a standard clinical evaluation tool for the disease.

The measurements collected by the app corresponded with what was observed by the physicians in the clinic.

After clinical trials, researchers hope the app could provide physicians and patients with a new way to monitor the disease.

"The ability to remotely monitor patients on a much more frequent basis, more accurately track the symptoms and progression of the disease, and monitor the impact of exercise, sleep, and medications and their side effects holds the potential to transform how we treat Parkinson's disease," said Dr. Christopher Tarolli, a neurologist at URMC and co-author of the study.

https://www.upi.com/Health_News/2018/03/26/Tracking-Parkinsons-symptoms-with-phone-app-could-improve-treatment/6671522083274/?utm_source=sec&utm_campaign=sl&utm_medium=2

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Supporting Parkinson's patients

March 25, 2018  BY STEPHANIE BRZEZINSK

TRAVERSE CITY — Traverse City, Michigan resident Hettie Molvang said she has facilitated Parkinson’s Network North meetings for about 15 years with the goal of providing information and getting people talking to each other.

“The support group is an opportunity to talk to other Parkinsonians in a safe place,” she said. “Parkinson’s is a chronic, multi-system neurodegenerative condition. Everything begins to slow down. Parkinson’s has a tendency to steal everything you’ve got.”

The nonprofit started in 1984 with one meeting time, but Molvang said high attendance led them to add a second session to their monthly schedule several years ago.

“It has grown considerably because Parkinson’s is doubling the world over,” she said. “It is now considered an epidemic.”

Molvang said about 1 million people have Parkinson’s disease in the United States, making the disease second to Alzheimer’s. That number is expected to double within a couple decades because of injuries and environmental factors, she said.

Molvang said the biggest problem is that people are often diagnosed 10-20 years after they show the first signs of Parkinson’s disease, such as loss of smell and slower movements.

“You are not aware you have it until you have a motor symptom,” she said. “No two Parkinsonians are alike. This makes it very difficult to treat.”

Often, Molvang said, Parkinson’s disease is thought of as a condition affecting older people, but today’s research shows this is not true.

“We’re finding that people with Parkinson’s are younger now,” she said, naming Michael J. Fox as an example. Fox was 29 years old when he was diagnosed.

Though there is no cure for Parkinson’s disease, Molvang said regular exercise is one of the best ways to lessen symptoms.

Occupational therapist Karen Getz agreed. Getz currently teaches the “Moving Forward” class at the Betsie Hosick Health and Fitness Center in Frankfort. The center added this class to the schedule of cardio and balance events in early February.

“There’s definitely a need in our community for support with people with Parkinson’s,” she said. “They want direction. The class puts control back in their hands with research-based exercise.”

Getz said she leads participants through “large, amplified movements” that repeat so Parkinson’s patients can regain a normal level of function. Counting, singing and socializing also help improve the voice.

The sessions make everyone tired, Getz said, but they are worth it. She added that anyone is welcome.

“We encourage people to be strong,” she said. “It’s not just for people with Parkinson’s. We want to make it all-inclusive.”

The “Moving Forward” class meets at 11 a.m. every Thursday at the Betsie Hosick Health and Fitness Center. Call 231-352-9661 for more details.

Parkinson’s Network North’s daytime group meets at 10 a.m. on the fourth Wednesday of each month at the Traverse City Senior Center. The evening meeting starts at 6 p.m. on the first Tuesday of the month at Munson Community Health Center.

Support groups are also available in Frankfort and Suttons Bay. Caregivers and patients are invited to attend, discuss resources and learn from speakers.

People can call 231-947-7389 if interested in volunteering or learning more about Parkinson’s Network North.

http://www.record-eagle.com/news/local_news/supporting-parkinson-s-patients/article_a5a85402-1690-5489-a303-e5b2e7022ae5.html

Tracking LRRK2-Parkinson’s Progression for Better Trial Design

March 23, 2018

Parkinson’s disease comes in many flavors, posing a challenge for researchers who design clinical trials in their search for treatments. Knowing how the disease progresses naturally may better their chance of success. A longitudinal study from the LRRK2 Ashkenazi Jewish Consortium provides just such data. Researchers led by Rachel Saunders-Pullman, Mount Sinai Beth Israel Medical Center in New York, compared how PD progressed in patients who carry the G2019S LRRK2 mutation and people with sporadic disease. Confirming previous studies, they found that motor symptoms advanced more slowly in mutation carriers. The results appear in the March 1 JAMA Neurology.

• The study maps progression in people with and without the G2019S LRRK2 mutation.
• Motor symptoms worsen more slowly in G2019S-PD.
• The data may help clinicians better design clinical trials.

The size of the new data set and the length of follow-up supersede similar studies. “It is a substantive and important study, one of the biggest involving LRRK2 patients,” noted Mark Cookson at the National Institutes of Health, Bethesda, Maryland. Carole Ho of Denali Therapeutics in South San Francisco was encouraged by the quality of the study. “We are using the new data to design trials to test LRRK2 inhibitors,” she told Alzforum. “Knowing the natural course of disease is very important.”

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial PD, but their penetrance and prevalence varies greatly between populations. Also, while some LRRK2 variants slow down disease progression, others speed it up (Oosterveld et al., 2015). Because LRRK2-PD shares symptoms and pathology with the sporadic form, researchers believe that drugs targeting the kinase may help most PD patients. Moreover, because the kinase is overactive in disease, it is a tractable target for drug development. Pfizer, Merck, Glaxo-SmithKline, and Genentech have created an array of LRRK2 inhibitors. As they have begun testing them in clinical trials, the need to understand how PD progresses in LRRK2-PD patients has become urgent.

PD Trajectories. Motor symptoms develop more slowly in G2019S-LRRK2 (orange) than in idiopathic PD (blue). [Courtesy of Saunders-Pullman et al., JAMA Neurology, © (2018) American Medical Association. All rights reserved.]

Longitudinal studies of PD caused by G2019S, the most common LRRK2-activating mutation, are sparse, small, or cross-sectional (Healy et al., 2008; Alcalay et al., 2013; Yahalom et al., 2014). The Parkinson’s Progression Markers Initiative (Oct 2013 news) tracks data from LRRK2-PD patients, but until recently, was limited to a single follow-up visit at one year.

To chart progression specifically in G2019S LRRK2 PD, Saunders-Pullman analyzed data from 144 patients with the mutation and 401 with sporadic PD. The patients were recruited from the LRRK2 Ashkenazi Jewish Consortium. In this population, the G2019S mutation causes up to 15 percent of PD cases, compared to 1 to 2 percent worldwide, said Saunders-Pullman. Participants had undergone up to six extensive evaluations over six years. Using the Unified Parkinson’s Disease Rating Scale III, clinicians scored them on motor skills such as talking, finger tapping, walking, and standing up. The scale also measured tremor, rigidity, and slowness. Participants took the Montreal Cognitive Assessment, which tests memory, attention, concentration, language, and awareness of time and place. All examinations were done when patients were in the “on” state, meaning when they had maximum benefit from their PD medication.

After adjusting for sex, age, disease duration, and PD medication dosing at baseline, G2019S LRRK2 mutation carriers declined some 30 percent slower on the UPDRS than did those with sporadic PD (image above). The milder motor course is consistent with other studies.

Cognitive impairment followed a similar trend, though the difference was not statistically significant. “The cognitive phenotype is so variable that it’s not surprising it didn’t reach significance,” said Cookson. Nonetheless, Saunders-Pullman believes the trend reflects a real difference, and added that full neuropsychological assessments in a subgroup of patients should help resolve the issue.

Why the difference in progression? There is no easy answer, said Cookson, noting that PD pathology is very variable. “Sometimes you see different pathology even in the same family with the same mutation,” he said. Indeed, Lewy body pathology, a hallmark of idiopathic PD, surfaces in only some patients with the G2019S mutation (Kalia et al., 2015). It is still unclear whether the milder G2019S disease course is due to a subgroup of patients with more benign pathology bringing down the average, or if most mutation carriers have less aggressive pathology, noted the authors.

Matthew Farrer, University of British Columbia, Vancouver, Canada, welcomed the new findings, but said that future studies would benefit from longer follow-up. He noted that results for 62 of the patients were limited to a single time point, and only seven patients had five or more years of follow-up. Adding more patients with more data points should refine the progression model and help scientists address the question of how a person’s age of onset correlates with disease severity across different forms of PD (Trinh et al., 2014). 

Will the new data improve the design of LRRK2 inhibitor trials? Ho said it is helping to calculate the number of patients needed for a Phase 1b study.

“I think it’s a very exciting time in the PD world,” said Saunders-Pullman. “The hope is that with more homogenous cohorts, we’ll find signals more easily.”—Marina Chicurel

REFERENCES

Alzpedia Citations

1. Leucine-rich repeat kinase 2 (LRRK2)

https://www.alzforum.org/news/research-news/tracking-lrrk2-parkinsons-progression-better-trial-design

Handling dementia: A caregiver's guide

March 24, 2018

Around six million Americans have Alzheimer's disease, and that number is expected to reach 15 million by 2060. In 2017, 47 million more had preclinical AD; they suffer neurodegeneration and/or amyloidosis, the beginnings of those amyloid tangles that are thought to (sometimes) characterize AD. And around six million in the U.S. and Canada have a non-AD dementia that affects behavior and may cause apathy, disinhibition, personality changes and loss of executive function—that is, the ability to plan ahead and get organized—like Parkinson's disease or primary progressive aphasia syndromes (affecting speech) or a form of dementia that can happen as a result of vascular disease, high blood pressure, stroke, diabetes or idiopathic normal pressure hydrocephalus (iNPH).

But dementia affects far more people than that. Loved ones, caregivers, friends and family all are affected. One study in JAMA found that caregivers 66 and older were at a 63 percent increased relative risk of dying than non-caregivers. And AgingCare.com says that fully 30 percent of caregivers die before the person for whom they are caring.

The strain, anger, guilt, remorse and stress are devastating and make it harder on both the patient and the caregiver. That's why a new Florida Atlantic University College of Nursing study is so groundbreaking. The researchers designed and tested a program to facilitate communication between people suffering from dementia and their caregivers. The results of their 10-week study have been promising for both.

The study was a home-based intervention called CARE, or Caring About Relationships and Emotions. Fifteen older couples agreed to meet with a facilitator, alone and together, once a week to discuss and develop their communication strategies, both verbal and nonverbal.

The researchers took this approach because of the frustration caregivers often feel when they mistakenly engage their loved one in a way that raises tension on both sides. For example, a caregiver may choose to go over a family photo album and ask the afflicted spouse if he or she remembers the family vacation in Wyoming in 2005. When the person with dementia cannot remember, both parties end up feeling terrible. Clearly, that's not an effective communication strategy. The researchers call it a "disabling conversation." They want caregivers to understand that you can't jar a person's memory when much of it has faded away. A different approach is what this intervention study is all about.

Step by step, the researchers took the caregiver through various ways to promote interaction without increasing tension and unhappiness. And they showed how to help a dementia patient become engaged in sociable conversation.

Interestingly, care receivers with moderate dementia improved more than caregivers. Care receivers increased their verbal and nonverbal social communication, were more interested and engaged, maintained eye contact, responded to questions, stayed on topic, and even joked with and teased their partners. And that, in turn, decreased caregiver stress.

How Can You Take Advantage of These Techniques?

The Alzheimer's Association (www.alz.org) has local chapters across the country that are aware of this study and of these communication techniques—and they offer online help in the form of programs and classes, plus a 24/7 helpline: 1-800-272-3900. They can put you in touch with a medical professional who can first properly diagnose the condition (remember, not all dementia is Alzheimer's), and then help you move forward from there.

Getting the right diagnosis is a crucial first step. For example, dementia caused by iNPH may be completely reversed with the proper treatment. It's estimated that more than 700,000 Americans have iNPH, but less than 20 percent receive an appropriate diagnosis (the person's gait is a tip-off, and a good doctor will know that). It's often misdiagnosed as Alzheimer's or Parkinson's disease.

There's a lot to know about how to handle AD and other dementias, so if you or a loved one is affected, the sooner you have answers the better off everyone will be.

(c) 2018 Michael Roizen, M.D. and Mehmet Oz, M.D.

http://www.texarkanagazette.com/news/features/story/2018/mar/24/handling-dementia-caregivers-guide/718956/