Simple Screening Tool Predicts Parkinson’s Patients At Risk of Dementia

MedicalResearch.com Interview with:

Benjamin Dawson, B.Sc.  MD Candidate 2020

Benjamin Dawson

Benjamin Dawson, B.Sc.
MD Candidate 2020

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications – it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia.

While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder (‘acting out’ the dreams at night).

When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia. Continue reading

Parkinson’s: Transcranial Stimulation of Motor and Cognitive Regions Reduced Gait Freezing

MedicalResearch.com Interview with:

Prof. Jeffrey Hausdorff PhD Director of the Center for the Study of Movement, Cognition and Mobility Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience Tel Aviv Medical Center

Prof. Hausforff

Prof. Jeffrey Hausdorff PhD
Director of the Center for the Study of Movement, Cognition and Mobility
Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience
Tel Aviv Medical Center

MedicalResearch.com: What is the background for this study?

 Response: Many people with Parkinson’s disease suffer from a disturbing symptom referred to as “freezing of gait”. When freezing occurs, the person’s feet inexplicably become stuck to the floor and he or she is unable to move forward, despite efforts to walk. Initially, the problem can last just a few seconds and occur very infrequently. As the problem progresses, however, freezing can last many seconds, occurring frequently throughout the day. This can lead to a very frustrating situation that may also be dangerous. People with freezing of gait have an increased risk of falls and reduced health-related quality of life.

The behavioral manifestation of freezing of gait is a problem with walking, i.e., it is a “motor” symptom. However, there is also evidence that deficits in specific aspects of cognitive function (i.e., executive function) may also contribute to freezing of gait. The goals of the present work were to use non-invasive brain stimulation to better understand if these cognitive deficits are indeed in the causal chain and if non-invasive brain stimulation that simultaneously targets both motor and cognitive brain areas that are believed to involved with freezing have a better impact on freezing and related symptoms than stimulation that targets only motor brain areas or sham stimulation.

Continue reading

Genetics Underlies Differences in Parkinson’s Disease Progression

MedicalResearch.com Interview with:

Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003

Dr. Saunders-Pullman

Rachel Saunders-Pullman, MD, MPH
Associate Professor of Neurology
Icahn School of Medicine at Mount Sinai
Chief, Movement Disorders, Mount Sinai Beth Israel
Co-Director Clinical/Translational Research and Research Mentoring
Movement Disorders, Department of Neurology,
Mount Sinai Beth Israel
New York, NY 10003

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features.

To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score.

We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08).

Continue reading

Study Finds Modest Survival Increase in Parkinson’s Patients Who Receive Deep Brain Stimulation

MedicalResearch.com Interview with:
Dr. Frances M. Weaver PhD
Hines VA Hospital
Center of Innovation for Complex Chronic Healthcare
Hines, IL 60141

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Research has shown that deep brain stimulation (DBS) for Parkinson’s disease (PD) improves motor function and this improvement is sustained. There is also improvement in quality of life after DBS. However, it is not known whether DBS also effects survival. A few studies that have examined survival have had mixed results.

In the current study we compared survival for a large cohort of persons with Parkinson’s disease who underwent DBS to a match group of persons with PD who were managed medically.

We found a modest improvement in survival for persons with Parkinson’s disease who underwent DBS compared to individuals who did not.

Continue reading

Tapeworm Drug May Be Repurposed To Fight Parkinson’s Disease

MedicalResearch.com Interview with:

Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University

Dr. Mehellou

Dr. Youcef Mehellou PhD
Lecturer in Medicinal Chemistry
Cardiff School of Pharmacy and Pharmaceutical Sciences
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Over the last decade or two, there has been many reports linking genetic mutations to the pathogenesis of Parkinson’s disease (PD). Among the proteins that have been found to be mutated in PD is a protein called PINK1. Indeed, PINK1 mutations that disturb its function in cells were found to be causal of PD in humans. Subsequent studies showed that PINK1 is a major player in maintaining healthy neurons. This is because it is one of the components involved in controlling the quality of the mitochondria, an organelle within the cell, and it does this by triggering the disposal of unhealthy mitochondria. Overall, studies into PINK1 indicated that the activation of PINK1 as a plausible strategy for maintaining health neurons and hence slowing down the development and progress of Parkinson’s disease.

Continue reading

Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London

MedicalResearch.com: What is the background for this study?

Response: Exenatide is a synthetic version of a naturally occurring protein – exendin-4 – that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.

Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.

Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.

As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.

Continue reading

Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

Continue reading

Vagotomy May Point To Gut Origin of Parkinson’s Disease

MedicalResearch.com Interview with:

Karin Wirdefeldt, MD, PhD</strong> Associate professor Karolinska Institutet Stockholm, Sweden

Dr. Wirdefeldt

Karin Wirdefeldt, MD, PhD
Associate professor
Karolinska Institutet
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has been hypothesized that Parkinson’s disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson’s disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected).

Continue reading

Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers

MedicalResearch.com Interview with:

Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland

Dr. Yong Cheng

Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland

MedicalResearch.com: What is the background for this study?

Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.

Continue reading

Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia

MedicalResearch.com Interview with:

Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC.

Dr. Charbel Moussa

Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson’s Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.

Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer’s Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).

Continue reading