MedicalResearch.com Interview with:Blayne Welk, MD, MSc,FRCSC
Assistant Professor of Surgery
Western University
London, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prior research has demonstrated that gadolinium, which may be used during MRI scans to help visualise the body organs, can be deposited in the body, and remain there for years. The US FDA released a notice last year stating that further research was needed to evaluate the clinical implications of these brain deposits. One of the areas that gadolinium is deposited is the brain, specifically in two regions which control voluntary movement (the globus pallidus and dentate nucleus). Damage to these areas could cause symptoms of Parkinsonism. We used administrative data from Ontario, Canada to evaluate whether people who underwent MRI scans with gadolinium had a higher risk of developing Parkinsonism in the future. In this study, we did not demonstrate an increased risk of Parkinsonism in patients exposed to gadolinium.
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MedicalResearch.com Interview with:
Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, DenmarkMedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes.
Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells.
Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson's disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson's disease.
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MedicalResearch.com Interview with:
Helena Nyström MD, PhD Candidate
Department of Community Medicine and Rehabilitation
Umeå University
Umeå, Sweden
Medical Research: What is the background for this study?
Response: Parkinson’s disease (PD) has an insidious onset and the prodromal phase, preceding the onset of the characteristic PD symptoms, may last for decades. Most prodromal signs previously reported are of non-motor type, such as sleep and mood disorders. However, recent studies have reported balance problems and an increased risk of accidental injuries in the last 3-5 years before diagnosis of Parkinson’s disease , and in a previous study we found a lower muscle strength at military conscription in men who were diagnosed with Parkinson’s disease three decades later. In this study, we aimed to investigate if such subtle strength deficits may translate into an increased risk of fall-related injuries.
Medical Research: What are the main findings?
Response: The median study time was 20 years before the diagnosis of Parkinson’s disease , and during this time more individuals with PD (18%) than controls (11.5%) had at least one fall-related injury. The risk was most increased in the last few years before the diagnosis of Parkinson’s disease , but a difference between the groups appeared already a decade before the PD diagnosis. The risk of hip fracture was increased during the entire study time of 26 years before the diagnosis of Parkinson’s disease .
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More Interviews on Neurological Disorders on MedicalResearch.com
MedicalResearch.com Interview with:
Professor Carl E Clarke
Professor of Clinical Neurology and Honorary Consultant Neurologist Department of Neurology City Hospital
Sandwell and West Birmingham Hospitals NHS Trust
Birmingham UKMedical Research: What is the background for this study? Dr. Clarke: Parkinson's disease causes problems with activities of daily living that are only partially treated by medication and occasionally surgery. Physiotherapy and occupational therapy services like Ck Physio are traditionally used later in the disease, but it is unclear whether they are clinically and cost-effective in Parkinson's disease.
Medical Research: What are the main findings?Dr. Clarke: We performed a large pragmatic randomised trial to evaluate the clinical and cost-effectiveness of individualized physiotherapy and occupational therapy in Parkinson's disease. The PD REHAB trial was a multicenter, open label, parallel group, controlled efficacy trial. 762 patients with mild-moderate Parkinson’s disease were recruited from 38 sites across the United Kingdom. For patients with mild to moderate Parkinson disease, there were no clinically meaningful benefits in activities of daily living or quality of life associated with physiotherapy and occupational therapy.
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MedicalResearch.com Interview with:
Brian S. McKay, Ph.D
Associate Professor
Department of Ophthalmology and Vision Science
University of Arizona
Medical Research Building, Room 212
Tucson, AZ 85724Medical Research: What is the background for this study?
Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics.
Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA.
Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD.
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MedicalResearch.com Interview with:
Dr. Ilse S. Pienaar
Honorary Lecturer in Neuroscience at Imperial College London
(& Snr. Lecturer in Cellular Pathology, Northumbria University)
Centre for Neuroinflammation & Neurodegeneration
Division of Brain Sciences Faculty of Medicine
Imperial College London
Hammersmith Hospital Campus
London United Kingdom
Medical Research: What is the background for this study? What are the main findings?Dr. Pienaar: A highly heterogeneous brainstem structure, the pedunculopontine nucleus (PPN) has been deemed a promising target for the delivery of deep-brain stimulation (DBS), to alleviate aspects of Parkinson's disease (PD), especially gait and postural instability. However, optimal therapeutic targeting of the PPN has been hampered due to DBS being unable to discriminate between cell types being targeted. We optomised a novel technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADD) in a rat model of PD, by which to target only the PPN cholinergic neurons. A series of behavioral tests revealed that selective stimulation of the PPN cholinergics completely reverses gait problems and postural instability in the PD rats.
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MedicalResearch.com Interview with:
Ron Postuma, MD, MSc
Associate Professor
Department of Neurology
Montreal General Hospital
Montreal, Quebec
Medical Research: What is the background for this study? What are the main findings?Dr. Postuma: The background is that we often think about Parkinson’s Disease as a single disease. However, every clinician knows that there is a great deal of variability from patient to patient. If we can understand the main aspects that separate patients into groups, we can target therapy better.
The analysis used a semi-automated means to divide Parkinson’s patients into groups, using extensive information about motor and non-motor aspects of disease. We found that the non-motor symptoms, especially cognition, sleep disorders, and blood pressure changes were the most powerful predictors of which group a patient would be in. Based on these non-motor (and some motor aspects), the most accurate way to divide patients was into three groups - diffuse (many non-motor symptoms), pure motor, and intermediate (halfway between the other). We then followed patients over time. The diffuse group had, by far, the worse prognosis. This was not only for the non-motor aspects, but the motor as well. (more…)
MedicalResearch.com Interview with:
Dr. Lori P. Altmann
Department of Speech, Language, and Hearing Sciences
Center for Movement Disorders and Neurorestoration
University of Florida, Gainesville, Florida
Medical Research: What is the background for this study? What are the main findings?
Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor performance usually declines. These “dual task effects” are exaggerated in healthy older adults, and are even more pronounced in people with Parkinson disease (PD). Our study investigated dual task effects during cycling in healthy older adults and people with Parkinson disease. In contrast to most studies of this type which typically contrast dual task effects of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely difficult. One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the cognitive task.
Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped up, and the amount they sped up was directly related to the difficulty of cognitive tasks. In the easiest task, cycling speed increased by an average of about 25%, With some participants actually doubling their single task speed. There was no evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the cognitive tasks either remained the same or got slightly better. Interestingly, people with Parkinson disease still showed faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults.
We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional resources that can be used for both motor and cognitive processing. We believe the findings haven’t been documented before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on neurotransmitters. Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting arousal-based increases in attentional resources.
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MedicalResearch.com Interview with:
Line Kenborg, MSc, PhD
Survivorship Unit
Danish Cancer Society Research Center
Copenhagen
Medical Research: What is the background for this study? What are the main findings?
Response: The hypothesis that head injuries increase the risk for Parkinson disease has been examined in many studies during the past decades, but the findings have been highly inconsistent. We have previously examined the hypothesis in a study based on information on head injuries and Parkinson disease from the Danish National Hospital Registry. In this study, we found a positive association between a hospital contact for a head injury in middle or late adulthood and a diagnosis of Parkinson disease. The reported association, however, was almost entirely due to injuries that occurred during the months preceding the first hospital contact for Parkinson disease. Because we used information from registries, we lacked detailed diagnostic information to distinguish Parkinson disease from other types of parkinsonism, and we had no information on milder head injuries and head injuries in early life. So we wanted to study whether head injuries throughout life increased the risk for Parkinson disease in the largest interview-based case-control study to date including patients with a verified diagnosis of Parkinson disease. The main finding of our study is that we do not find any association between head injuries and Parkinson disease.
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MedicalResearch.com Interview with:
Filip Scheperjans MD
Department of Neurology
Helsinki University Central Hospital
Department of Neurological Sciences
University of Helsinki, Helsinki, Finland
Medical Research: What is the background for this study? What are the main findings?
Dr. Scheperjans: In Parkinson’s disease (PD), the first neurodegenerative changes are seen in the olfactory bulb and enteric nervous system. Correspondingly, most Parkinson’s disease patients suffer from hyposmia and gastrointestinal symptoms, frequently years before motor symptoms evolve. Therefore, it has been suggested that an environmental factor acting through the nose or gut, could be involved in Parkinson’s disease. Interestingly, those two habitats are where our body gets mostly exposed to environmental agents, including microbes. Previous attempts to identify microbes related to Parkinson’s disease pointed to Helicobacter pylori and small intestinal bacterial overgrowth, but in the end had been somewhat inconclusive. But there possibly was a signal. We saw next generation sequencing approaches as a new opportunity to revisit the microbe theory in PD. Studies of gut microbiome composition in neurodegenerative disease have not been published before, although alterations in gut microbiota have been demonstrated in many other diseases and gut microbiota are in close interaction with the central nervous system.
The fecal microbiome of Parkinson’s disease subjects clearly differed from that of matched controls and this difference was independent of the potential confounders that we assessed. The most significant finding was that the abundance of bacteria from the Prevotellaceae family was reduced by 78% in Parkinson’s disease patients. A low abundance of Prevotellaceae was 86% sensitive for PD, but rather unspecific. However, a combination of 4 bacterial families increased specificity for PD to 90%. So microbiome analysis performed quite well in distinguishing Parkinson’s disease patients from control subjects. Another interesting finding was that, within the Parkinson’s disease group, abundance of Enterobacteriaceae bacteria was related to the motor symptoms of patients. They were positively associated with the severity of postural instability and gait difficulty.
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MedicalResearch.com Interview with: Daniel Weintraub, M.D.
Associate Professor of Psychiatry and Neurology
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA 19104-2676
Parkinson's Disease Research, Education and Clinical Center (PADRECC)
Mental Illness Research, Education and Clinical Center (MIRECC)
Philadelphia Veterans Affairs Medical Center
Medical Research: What are the main findings of the study?Dr. Weintraub: That there is mixed evidence for the efficacy of naltrexone in the treatment of impulse control disorders in Parkinson’s disease, and the evidence is sufficient to support further study of this compound class for this indication. In addition, the study demonstrates that it is possible to conduct a clinical trial in this area.
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MedicalResearch Interview with:Richard Gray
Professor of Medical Statistics
Clinical Trial Service Unit
Richard Doll Building, Oxford
MedicalResearch: What are the main findings of the study?Prof. Gray: We found that, when we asked patients with Parkinson’s disease how their drugs affected their overall quality of life, the older drug levodopa was better than newer, more expensive drugs and that this benefit persisted for at least seven years from starting treatment.
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MedicalResearch.com Interview with: Priv. Doz. Dr. Carsten Buhmann
Department of Neurology
University Medical Center Hamburg-Eppendorf
Hamburg, Germany.
MedicalResearch.com: What are the main findings of the study?Answer: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no negative but rather a beneficial effect on driving in patients with Parkinsons´s disease (PD). Driving not only was superior in even more clinically affected PD patients with DBS compared with PD patients without DBS but also patients with DBS drove better with stimulation than with levodopa.
This might reflect favorable driving-relevant nonmotor effects due to STN-DBS.
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MedicalResearch.com: Interview with:Michelle M. Mielke, Ph.D.
Associate Professor
Department of Health Sciences Research
Division of Epidemiology
Mayo Clinic 200 First Street SW
Rochester, MN 55905
MedicalResearch.com: What are the main findings of the study?Dr. Mielke: Among Parkinson’s disease (PD) patients, plasma levels of ceramides and monohexylceramides were higher in patients with cognitive impairment or dementia compared to patients who were cognitively normal. Levels of these lipids were also higher in the combined group of PD patients compared to non-PD controls but the number of controls were small.
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MedicalResearch.com Interview with:Rodolfo Savica, MD, MSc
Department of Neurology, College of Medicine
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota
MedicalResearch.com: What are the main findings of this study?Dr. Savica:This study is the first in North America to explore the incidence of DLB and PDD in a population based sample. We found that the overall incidence of dementia with Lewy bodies (DLB), considered the second leading cause of neurodegenerative dementia after Alzheimer`s disease, is lower than that of Parkinson`s disease (PD), increases steeply with age, and is markedly higher in men than in women.
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MedicalResearch.com: Interview with Alice Chen-Plotkin, MD
Assistant Professor
Department of Neurology
University of Pennsylvania School of Medicine
MedicalResearch.com: What are the main findings of the study?Answer: Parkinson's disease (PD) is an incurable neurodegenerative disease. Many neurons die, but the neurons that make dopamine (dopaminergic neurons) are particularly vulnerable. We think that the disease actually starts well before the time when people show clinical symptoms. We were therefore interested in finding proteins from the blood that correlated with better or worse dopaminergic neuron integrity. Since it's hard to access the dopaminergic neurons directly, we looked at a tracer that labels the ends of the dopaminergic neurons in people who do not have Parkinson's disease but are at high risk for developing it, and we also looked at the age at onset of PD in people who are already symptomatic. Screening just under 100 different proteins from the blood, we found that higher plasma levels of apolipoprotein A1 (ApoA1) were correlated with better tracer uptake in the people who did not yet have PD, and with older ages at onset in the people who already had PD. These data suggest that plasma ApoA1 may be a marker for PD risk, with higher levels being relatively protective.
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MedicalResearch.com Interview with: Kalipada Pahan, Ph.D.
The Floyd A. Davis, M.D., Endowed Chair of Neurology
Professor
Departments of Neurological Sciences, Biochemistry and Pharmacology
Rush University Medical Center
1735 West Harrison St, Suite 320 Chicago, IL 60612
MedicalResearch.com: What are the main findings of the study?Dr. Pahan: While different toxins and a number of complex genetic approaches are used to model Parkinson’s disease in mice, this study delineates that simple castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice. This simple, but persistent, model may be helpful in discovering drugs against Parkinson’s disease. Furthermore, these results suggest that sudden drop of testosterone level could trigger Parkinson’s disease.
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MedicalResearch.com eInterview with Dr. Emanuele Cereda
Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo
Viale Golgi 19, 27100 Pavia, ItalyMedicalResearch.com: What are the main findings of the study?Dr. Cereda: A large analysis of more than 100 studies shows that exposure to pesticides, or bug and weed killers, and solvents is likely associated with a higher risk of developing Parkinson’s disease.
MedicalResearch.com: Were any of the findings unexpected?Dr. Cereda: In first instance I can say no as in every day clinical practice we frequently see patients reporting such exposure. Accordingly, it appears quite obvious to look at these exposures as risk factors. Unfortunately, from an epidemiologic point of view this is not enough! That's why we did this study. Amazing rather than surprising was the fact that commonly the sources of funding in the studies we retrieved and included in meta-analysis were health or health-related institutions, private foundations (mainly Parkinosn’s disease foundations), or government or para-government companies. No study acknowledged the involvement of any chemicals manufacturer!
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