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Premotor Symptoms as Predictors of Outcome in Parkinsons Disease: A Case-Control Study

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  • #16
    Scratch-and-Sniff Test Could Predict Parkinson’s Earlier Than Previously Thought

    http://neurosciencenews.com/scratch-...rkinsons-7433/

    Jo Bowyer
    Chartered Physiotherapist Registered Osteopath.
    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

    Comment


    • #17
      Interrupting Parkinson’s Disease


      http://neurosciencenews.com/parkinso...oxidants-7448/

      Northwestern Medicine scientists have identified a toxic cascade that leads to neuronal degeneration in patients with Parkinson’s disease (PD) and figured out how to interrupt it, reports a study to be published September 7 in the journal Science.

      Intervening with an antioxidant early in the disease process may break the degenerative cycle and improve neuron function in PD, the study showed.

      The scientists also discovered that mouse models of PD didn’t have the same abnormalities they found in human PD neurons, revealing the importance of studying human neurons to develop new therapies.

      Dr. Dimitri Krainc, the Aaron Montgomery Ward Professor and chair of neurology at Northwestern University Feinberg School of Medicine, is the study senior author. Lena Burbulla, a postdoctoral fellow in Krainc’s laboratory, is first author.

      The research was started about six years ago in Krainc’s lab at Massachusetts General Hospital and Harvard Medical School and was completed in the last four years at Feinberg.

      PD is the second most common neurodegenerative disorder, primarily caused by the death of dopamine-containing neurons in the substantia nigra, a region of the brain involved in motor control. While people naturally lose dopamine neurons as they age, patients with PD lose a much larger number of these neurons and the remaining cells are no longer able to compensate.

      Understanding how and why these neurons die is an important step in identifying treatments, Krainc said. While previous research indicated that the cellular mechanism behind the cell death involved the mitochondria and lysosomes, how these two pathways converge in dopamine neurons to cause cell death remained unknown up until now.

      Using human neurons from Parkinson’s patients, Krainc and colleagues identified a toxic cascade of mitochondrial and lysosomal dysfunction initiated by an accumulation of oxidized dopamine and a protein called alpha-synuclein. Specifically, the current study demonstrated that an accumulation of oxidized dopamine depressed the activity of lysosomal glucocerebrosidase (GCase), an enzyme implicated in PD. That depression in turn weakened overall lysosomal function and contributed to degeneration of neurons.

      The accretion of oxidized dopamine didn’t just interfere with lysosomes, however. Krainc and his colleagues discovered that the dopamine also damaged the neurons’ mitochondria by increasing mitochondrial oxidant stress. These dysfunctional mitochondria led to increased oxidized dopamine levels, creating a vicious cycle.

      “The mitochondrial and lysosomal pathways are two critical pathways in disease development,” said Krainc, who also is the director of the Center for Rare Neurological Diseases and a professor of neurological surgery and of physiology. “Combined with the alpha-synuclein accumulation, this study links the major pathological features of PD.”

      Once they had catalogued this toxic cascade, Krainc and his colleagues began looking for ways to interrupt it.
      Jo Bowyer
      Chartered Physiotherapist Registered Osteopath.
      "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

      Comment


      • #18
        The variability of the steps preceding obstacle avoidance (approach phase) is dependent on the height of the obstacle in people with Parkinson's disease

        http://journals.plos.org/plosone/art...l.pone.0184134

        Abstract


        Gait variability may serve as a sensitive and clinically relevant parameter to quantify adjustments in walking and the changes with aging and neurological disease. Variability of steps preceding obstacle avoidance (approach phase) are important for efficiency in the task, especially in people with Parkinson's disease (PD). However, variability of gait during the approach phase to obstacle avoidance in people with PD has been rarely reported, particularly when ambulating obstacles of different heights. The aim of the present study was to investigate the effects of obstacle height on step-to-step variability (step-to-step variability provides information on the variation between the "equivalent steps" for all trials, and walking variability (indicates the within-step variability of each, providing information about the modulations between the steps performed. of spatial-temporal parameters during the approach phase to obstacle avoidance in people with PD and neurologically healthy older people. Twenty-eight older people; 15 with PD and 13 neurologically healthy individuals (control group), participated in the study. Participants were instructed to walk at their preferred speed until the end of the pathway and to avoid the obstacle when it was present. Each subject performed 10 trials of the following tasks: unobstructed walking, low obstacle avoidance (3cm length, height equal ankle’s height, 60 cm wide), intermediate obstacle (3cm length, low plus high obstacle height divided by 2, 60 cm wide) avoidance and high obstacle avoidance (3cm length, knee’s height, 60 cm wide). The obstacle was positioned 4m from to the start position. The step-to-step and walking variability of the spatial-temporal parameters (acquiring with GAITRite®) of the four steps before obstacle avoidance were analyzed. MANOVAs were used to compare the data. PD group showed the characteristic gait deficits associated with PD. The obstacle increased the spatial-temporal variability (step–to-step and walking variability) during the approach phase to the obstacle. Specifically, both groups increased i) the step-to- step variability of the step length during low obstacle avoidance when compared to the other conditions; ii) the variability during low obstacle avoidance in the last step before obstacle (n-1) compared to higher obstacle avoidance; iii) variability during higher obstacle avoidance in further steps (n-3 and n-4). In conclusion, the presence of the obstacle during walking increased the variability of spatial-temporal parameters in older people with PD and the control group during the steps preceding obstacle avoidance. In addition motor planning (and motor adaptations) was initiated much earlier in the approach phase for the higher obstacle conditions compared to the low obstacle condition.
        Jo Bowyer
        Chartered Physiotherapist Registered Osteopath.
        "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

        Comment


        • #19
          Brain Rewiring in Parkinson’s Disease May Contribute to Abnormal Movement

          http://neurosciencenews.com/parkinso...nt-brain-7503/

          The study suggests the loss of dopamine may cause the brain to rewire in a maladaptive manner, contributing to impaired movement in Parkinson’s disease. These findings also suggest that there are fundamental problems with scientists’ traditional model of Parkinson’s disease, said senior author Mark Bevan, PhD, professor of Physiology at Northwestern University Feinberg School of Medicine.

          The prevailing consensus was that excessive patterning of the subthalamic nucleus (STN), a component of the basal ganglia, by the cerebral cortex was linked to the symptomatic expression of Parkinson’s disease, including muscle rigidity and slowness of movement, according to Bevan.

          “When one saw a burst of activity in the cortex that was consistently followed by an abnormal burst of activity in the STN, scientists assumed that the direct connection between the two was responsible,” Bevan said.

          Thus, Bevan and his colleagues, including lead author Hong-Yuan Chu, PhD, a post-doctoral fellow in the Bevan Lab, expected to see transmission in the cortex-to-STN pathway increase as dopamine levels dropped. Instead, they found the opposite: the strength of the pathway decreased massively.

          “Like most scientists who come across something unexpected, we thought we’d done something wrong,” Bevan said. “So, we used multiple, complementary approaches but everything pointed to the same conclusion.”

          Further investigation suggested abnormal activity in a more indirect pathway from the cortex to the STN, involving the globus pallidus, was responsible. Abnormal activity in the indirect pathway leaves the STN vulnerable to excessive excitation, triggering compensatory plasticity that ultimately proved to be harmful, according to the study.
          Jo Bowyer
          Chartered Physiotherapist Registered Osteopath.
          "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

          Comment


          • #20
            Key to Loss of Smell in Parkinson’s Discovered

            http://neurosciencenews.com/parkinsons-smell-loss-7528/

            Jo Bowyer
            Chartered Physiotherapist Registered Osteopath.
            "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

            Comment


            • #21
              Fatigue in early Parkinson's disease: the Norwegian ParkWest study


              http://onlinelibrary.wiley.com/doi/1...ene.13161/full

              Abstract

              Background and purpose


              Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis.

              Methods


              The study design was a prospective, controlled population-based longitudinal cohort study, comprising 181 de novo, drug-naïve patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year.

              Results


              Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment.

              Conclusion


              Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD-associated fatigue.
              Jo Bowyer
              Chartered Physiotherapist Registered Osteopath.
              "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

              Comment


              • #22
                Modeling Brain Connections to Understand Parkinson’s Disease

                http://neurosciencenews.com/parkinso...nections-7601/

                A computational study models the strength of basal ganglia connections between healthy and Parkinsonian brains.
                Jo Bowyer
                Chartered Physiotherapist Registered Osteopath.
                "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                Comment


                • #23
                  Brain disconnections may contribute to Parkinson's hallucinations

                  https://www.sciencedaily.com/release...0927093338.htm
                  Jo Bowyer
                  Chartered Physiotherapist Registered Osteopath.
                  "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                  Comment


                  • #24
                    ‘Cats-And-Dogs’ Test to Predict Dementia Among Parkinson’s Patients

                    http://neurosciencenews.com/parkinso...-cat-dog-7767/

                    Lead researcher Dr Rimona Weil (UCL Institute of Neurology) says that dementia is a serious concern among people with Parkinson’s, as the disease can often develop into dementia, but early warning markers are currently lacking.

                    The research team developed their idea for the test after noticing that many people with Parkinson’s say they have trouble reading CAPTCHA images, an online security check using distorted text to tell humans and computers apart.

                    They derived a test tasking participants to identify whether a distorted image depicts a cat or a dog. In their study of 20 people with Parkinson’s and 11 controls, those who struggled with the task also did poorly on more in-depth tests of overall cognitive performance, and had higher scores on a risk measure, previously developed by one of the UCL researchers, that uses cross-sectional data.
                    parkinsons-cat-dog-test-neuroscincenws.jpg?w=750.jpg
                    Jo Bowyer
                    Chartered Physiotherapist Registered Osteopath.
                    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                    Comment


                    • #25
                      Herbicide's link to Parkinson's disease

                      https://www.sciencedaily.com/release...1023140734.htm



                      The use of paraquat, which causes cell death via oxidative stress, is restricted in the United States and banned in the European Union, but the chemical is still used widely throughout Asia and the developing world, according to Chandel, also a professor of Cell and Molecular Biology. Ingestion of paraquat can lead to lung fibrosis or even death, but a 2011 study linked occupational use to an increased risk for Parkinson's disease, renewing interest in its impact on humans.

                      A major cause of Parkinson's is the loss of function in dopamine neurons in a small brain region called the substantia nigra pars compacta, according to previous research. Those neurons are known to be highly vulnerable to oxidative stress, leading scientists to hypothesize paraquat was linked to Parkinson's disease through this oxidative stress.

                      "Paraquat generates a lot of oxidants. Naturally those dopaminergic neurons will be the most susceptible to damage," Chandel said.

                      However, the mechanism by which paraquat created oxidants was unknown -- until now.

                      Chandel and his collaborators conducted a CRISPR-Cas9 positive-selection screen, creating thousands of cells, each with one individual gene turned off.

                      "We thought it was a metabolic protein that paraquat was activating to generate oxidants," Chandel said. "So we localized our work to the 3,000 genes that encode for metabolic proteins, rather than the 18,000 to 20,000 genes human cells have in total."

                      They exposed that subset of cells to paraquat -- the majority of cells died, but not all of them. Certain cells with knocked-out genes were resistant to paraquat, suggesting those genes may be responsible for the toxicity.
                      Jo Bowyer
                      Chartered Physiotherapist Registered Osteopath.
                      "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                      Comment


                      • #26
                        Detecting Parkinson’s disease from sustained phonation and speech signals


                        http://journals.plos.org/plosone/art...l.pone.0185613

                        Abstract


                        This study investigates signals from sustained phonation and text-dependent speech modalities for Parkinson’s disease screening. Phonation corresponds to the vowel /a/ voicing task and speech to the pronunciation of a short sentence in Lithuanian language. Signals were recorded through two channels simultaneously, namely, acoustic cardioid (AC) and smart phone (SP) microphones. Additional modalities were obtained by splitting speech recording into voiced and unvoiced parts. Information in each modality is summarized by 18 well-known audio feature sets. Random forest (RF) is used as a machine learning algorithm, both for individual feature sets and for decision-level fusion. Detection performance is measured by the out-of-bag equal error rate (EER) and the cost of log-likelihood-ratio. Essentia audio feature set was the best using the AC speech modality and YAAFE audio feature set was the best using the SP unvoiced modality, achieving EER of 20.30% and 25.57%, respectively. Fusion of all feature sets and modalities resulted in EER of 19.27% for the AC and 23.00% for the SP channel. Non-linear projection of a RF-based proximity matrix into the 2D space enriched medical decision support by visualization.
                        Jo Bowyer
                        Chartered Physiotherapist Registered Osteopath.
                        "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                        Comment


                        • #27
                          Dance your PhD contest 2017_ Exercise in Parkinson disease_Josefa Domingos

                          https://www.youtube.com/watch?v=gkeYR8H1Zqw
                          Last edited by Jo Bowyer; 03-11-2017, 05:53 AM.
                          Jo Bowyer
                          Chartered Physiotherapist Registered Osteopath.
                          "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                          Comment


                          • #28
                            Good Cells Gone Bad

                            http://neurosciencenews.com/pink-sno-parkinsons-7998/

                            A new study from The Scripps Research Institute (TSRI) is the first to show precisely how a process in nerve cells called the S-nitrosylation (SNO) reaction–which can be caused by aging, pesticides and pollution–may contribute to Parkinson’s disease.
                            Jo Bowyer
                            Chartered Physiotherapist Registered Osteopath.
                            "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                            Comment


                            • #29
                              High-accuracy detection of early Parkinson's Disease using multiple characteristics of finger movement while typing


                              http://journals.plos.org/plosone/art...l.pone.0188226

                              Abstract


                              Parkinson’s Disease (PD) is a progressive neurodegenerative movement disease affecting over 6 million people worldwide. Loss of dopamine-producing neurons results in a range of both motor and non-motor symptoms, however there is currently no definitive test for PD by non-specialist clinicians, especially in the early disease stages where the symptoms may be subtle and poorly characterised. This results in a high misdiagnosis rate (up to 25% by non-specialists) and people can have the disease for many years before diagnosis. There is a need for a more accurate, objective means of early detection, ideally one which can be used by individuals in their home setting. In this investigation, keystroke timing information from 103 subjects (comprising 32 with mild PD severity and the remainder non-PD controls) was captured as they typed on a computer keyboard over an extended period and showed that PD affects various characteristics of hand and finger movement and that these can be detected. A novel methodology was used to classify the subjects’ disease status, by utilising a combination of many keystroke features which were analysed by an ensemble of machine learning classification models. When applied to two separate participant groups, this approach was able to successfully discriminate between early-PD subjects and controls with 96% sensitivity, 97% specificity and an AUC of 0.98. The technique does not require any specialised equipment or medical supervision, and does not rely on the experience and skill of the practitioner. Regarding more general application, it currently does not incorporate a second cardinal disease symptom, so may not differentiate PD from similar movement-related disorders.
                              Last edited by Jo Bowyer; 02-12-2017, 06:07 PM.
                              Jo Bowyer
                              Chartered Physiotherapist Registered Osteopath.
                              "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                              Comment


                              • #30
                                High Intensity Exercise Delays Parkinson’s Progression

                                http://neurosciencenews.com/high-int...rkinsons-8159/
                                Jo Bowyer
                                Chartered Physiotherapist Registered Osteopath.
                                "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                                Comment

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