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

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

    http://journals.plos.org/plosone/art...l.pone.0161271

    Abstract

    Background

    To evaluate the association between the premotor symptoms and the prognosis of PD.

    Methods

    A total of 1213 patients who were diagnosed of PD from January 2001 to December 2008 were selected from the Taiwan’s National Health Insurance Research Database. Patients were traced back to determine the presence of premotor symptoms, including rapid eye movement sleep behavior disorder (RBD), depression, and constipation. Cox’s regression analysis was used to detect the risks between the occurrence of premotor symptoms and the outcome (including death, psychosis, accidental injury, dementia and aspiration pneumonia). In addition, the association between premotor symptoms and levodopa equivalent dosage (LED) was examined.

    Results

    Higher occurrence of death, dementia and aspiration pneumonia were identified in PD patients with premotor symptoms than without premotor symptoms (HR 1·69, 95% CI 1·34–2·14, p <0·001 for death; HR 1·63, 95% CI 1·20–2·22, p = 0·002 for dementia; HR 2·45, 95% CI 1·42–4·21, p = 0·001 for aspiration pneumonia). In a comorbidities-stratified analysis, PD patients with premotor symptoms showed significantly high risks of mortality and morbidity (dementia and aspiration pneumonia), especially in the absence of comorbidities. Independent predictors of mortality in PD were found to be higher age, male sex, constipation, RBD, RBD with constipation and depression, and diabetes. Furthermore, no significant differences of LED and subsequent accidental injury were noted between PD patient with or without premotor symptoms.

    Conclusion

    Premotor symptoms seem to be not merely risk factors, but also prognostic factors of PD.


    Looking beyond the brain in Parkinson’s disease: is the answer skin deep?
    http://blogs.biomedcentral.com/bmcse...ource=Teradata

    Parkinson’s disease pathology is not limited to the brain, but disrupts the function of multiple organ systems. An article recently published in BMC Neurology provides new insights into the pathological changes that occur in the skin during Parkinson’s disease, and may shed light on potential targets for a diagnostic biomarker
    Update 05/04/2017



    The underlying mechanism of prodromal PD: insights from the parasympathetic nervous system and the olfactory system

    https://translationalneurodegenerati...ource=Teradata

    Abstract

    Neurodegeneration of Parkinson’s disease (PD) starts in an insidious manner, 30–50% of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis. Prodromal stage of the disease, during which the disease pathology has started but is insufficient to result in clinical manifestations, offers a valuable window for disease-modifying therapies. The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons. In this review, we consider the two potential portals, the vagus nerve and the olfactory bulb, through which abnormal alpha-synuclein can access the brain. We review the clinical, pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD, including both the clustering and subtyping of symptoms and signs. Finally, we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.
    According to recent Movement Disorder Society criteria, early PD can be divided into three stages: preclinical PD (neurodegeneration has started yet without evident symptoms and signs); prodromal PD (symptoms and signs are present, but are still insufficient to define PD) and clinical PD (diagnosis of PD based on classical symptoms). The criteria are based upon probability and likelihood since it is not possible to identify prodromal PD with 100% certainty; probable prodromal PD is defined as a high likelihood (greater than 80%) and possible prodromal PD as a likelihood between 30 and 80% [4, 5]. The cardinal features of prodromal PD are non-motor and include constipation, hyposmia/anosmia, depression, REM sleep behavior disorder, orthostatic hypotension, and loss of heart rate variability [6]. Notably, many of the symptoms that emerge earlier in the disease course can be attributed to dysfunction in the peripheral nervous system or the peripheral part of the central nervous system, such as the vagus nerve (e.g. constipation), the sympathetic nervous system (e.g. orthostatic hypotension), or the olfactory bulb (hyposmia).
    Update 13/04/2017



    Probing Possible Reasons For Smell Loss


    http://neurosciencenews.com/alzheimers-olfaction-6637/

    Studies have shown that loss of the sense of smell can be among the first warning signs of diseases such as Alzheimer’s and Parkinson’s. Now a researcher at the Perelman School of Medicine at the University of Pennsylvania wants to shift the search for clues about this process back even further, to find out if there is a common factor responsible for the loss of smell that may also serve as an early warning signal for a number of neurodegenerative diseases. In a review published online in Lancet Neurology, Richard L. Doty, PhD, a professor of Otorhinolaryngology and director of the Smell and Taste Center, cites evidence that the common link could be damage to neurotransmitter and neuromodulator receptors in the forebrain – the front part of the brain.

    “We need to retrace the steps of the development of these diseases,” Doty said. “We know loss of smell is an early sign of their onset, so finding common factors associated with the smell loss could provide clues as to the pre-existing processes that initiate the first stages of a number of neurodegenerative diseases. An understanding of such processes could provide novel approaches to their treatment, including ways to slow down or stop their development before irreversible damage has occurred.”

    Currently, it’s is generally believed that the smell loss of various neurodegenerative diseases is caused by disease-specific pathology. In other words, different diseases can bring about the same loss of smell for different reasons. Doty’s review – the first of its kind – looked at many neurodegenerative diseases with varying degrees of smell loss and sought to find a common link that may explain such losses. He considered physiological factors as well as environmental factors like air pollution, viruses, and exposure to pesticides.

    “Ultimately, as each possibility was evaluated, there were cases where these factors didn’t show up, which ruled them out as potential universal biomarkers.”

    Doty did find compelling evidence for a neurological solution: Damage to the neurotransmitter and neuromodulator receptors in the forebrain – most notably, a system employing the neurochemical acetylcholine. Neurotransmitters are the chemicals that send signals throughout the brain. Neuromodulators influence the activity of neurons in the brain. The receptors receive the signals, and if they are damaged, it hurts the brain’s ability to process smells normally.

    “The good news is we can assess damage to some of the systems by evaluating their function in living humans using radioactive neurochemicals and brain imaging processes such as positron emission tomography (PET),” Doty said. “Unfortunately, few data are currently available, and the historical data of damage to neurotransmitter/neuromodulator systems, including cell counts from autopsy studies, are limited to just a few diseases. Moreover, quantitative data on a patient’s olfactory status is rarely available, especially prior to disease diagnosis.”

    Doty said the lack of early data is a problem across the board in the search for factors that may explain smell loss.
    Update 10/05/2017


    Ocular Tremor in Parkinson’s Disease: Discussion, Debate, and Controversy

    http://journal.frontiersin.org/artic...017.00134/full

    The identification of ocular tremor in a small cohort of patients with Parkinson’s disease (PD) had lay somewhat dormant until the recent report of a pervasive ocular tremor as a universal finding in a large PD cohort that was, however, generally absent from a cohort of age-matched healthy subjects. The reported tremor had frequency characteristics similar to those of PD limb tremor, but the amplitude and frequency of the tremor did not correlate with clinical tremor ratings. Much controversy ensued as to the origin of such a tremor, and specifically as to whether a pervasive ocular tremor was a fundamental feature of PD, or rather a compensatory eye oscillation secondary to a transmitted head tremor, and thus a measure of a normal vestibulo-ocular reflex. In this mini review, we summarize some of the evidence for and against the case for a pervasive ocular tremor in PD and suggest future experiments that may help resolve these conflicting opinions.



    Visual System Changes That May Signal Parkinson’s Disease

    http://neurosciencenews.com/parkinso...-changes-7061/

    Changes in the visual systems of newly diagnosed Parkinson’s disease patients may provide important biomarkers for the early detection and monitoring of the disease, according to a new study published online in the journal Radiology.

    “Just as the eye is a window into the body, the visual system is a window into brain disorders,” said lead researcher Alessandro Arrigo, M.D., a resident in ophthalmology at the University Vita-Salute San Raffaele of Milan, Italy.

    Parkinson’s disease is a neurodegenerative condition caused by neuronal loss in several brain structures. Parkinson’s disease is characterized by tremors, rigidity or stiffness throughout the body, and impaired balance and coordination.

    “Although Parkinson’s disease is primarily considered a motor disorder, several studies have shown non-motor symptoms are common across all stages of the disease,” Dr. Arrigo said. “However, these symptoms are often undiagnosed because patients are unaware of the link to the disease and, as a result, they may be under-treated.”

    Non-motor symptoms experienced by patients with Parkinson’s disease include visual alterations such as an inability to perceive colors, a change in visual acuity, and a decrease in blinking which can lead to dry eye.

    “These non-motor Parkinson’s symptoms may precede the appearance of motor signs by more than a decade,” Dr. Arrigo said.
    Update 12/07/2017




    Cortical and Striatal Reward Processing in Parkinson’s Disease Psychosis

    http://journal.frontiersin.org/artic...017.00156/full

    Psychotic symptoms frequently occur in Parkinson’s disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms, along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
    Update 24/04/2017



    Associations between cognitive impairment and motor dysfunction in Parkinson's disease

    http://onlinelibrary.wiley.com/doi/1.../brb3.719/full

    Abstract

    Introduction

    Numerous studies have been carried out to explore the potential association between neurologic deficits and variable clinical manifestations of Parkinson's disease (PD). The aim of our study was to investigate the association between cognitive performance and motor dysfunction in Chinese patients with PD.
    Methods

    Data from 96 patients with PD were obtained from the Parkinson's disease patient cohort database of Huashan Hospital. All participants underwent a comprehensive neuropsychological evaluation to assess cognitive status, that included scoring on the Mini-mental state examination (MMSE), followed by more detailed cognitive assessment on five main cognitive domains (verbal memory, nonverbal memory, visuospatial function, language and attention/executive function). Correlations between cognitive and motor scores were investigated after controlling for age, disease duration, education, and gender.
    Results

    We report a significant correlation between subdomains of cognitive impairment and motor dysfunction using analyses of the multiple linear regression. Notably, executive function and attention was significantly associated with bradykinesia and rigidity, while visuospatial function was associated with bradykinesia and tremor.
    Conclusions

    The association between motor dysfunction and cognitive decline in PD might highlight deficits represented by a shared neurochemical pathway.
    Update 16/05/2017




    No relevant association of kinematic gait parameters with Health-related Quality of Life in Parkinson’s disease

    http://journals.plos.org/plosone/art...l.pone.0176816

    Abstract

    Background

    Health-related Quality of Life (HrQoL) is probably the most important outcome parameter for the evaluation and management of chronic diseases. As this parameter is subjective and prone to bias, there is an urgent need to identify objective surrogate markers. Gait velocity has been shown to be associated with HrQoL in numerous chronic diseases, such as Parkinson’s disease (PD). With the development and wide availability of simple-to-use wearable sensors and sophisticated gait algorithms, kinematic gait parameters may soon be implemented in clinical routine management. However, the association of such kinematic gait parameters with HrQoL in PD has not been assessed to date.

    Methods

    Kinematic gait parameters from a 20-meter walk from 43 PD patients were extracted using a validated wearable sensor system. They were compared with the Visual Analogue Scale of the Euro-Qol-5D (EQ-5D VAS) by performing a multiple regression analysis, with the International Classification of Functioning, Disability and Health (ICF) model as a framework.

    Results

    Use of assistive gait equipment, but no kinematic gait parameter, was significantly associated with HrQoL.

    Conclusion

    The widely accepted concept of a positive association between gait velocity and HrQoL may, at least in PD, be driven by relatively independent parameters, such as assistive gait equipment.
    Update 26/05/2017




    Pain in Parkinson’s Disease

    https://noijam.com/2017/06/23/pain-i...nsons-disease/

    Update 24/06/2017




    Forward flexion of trunk in Parkinson's disease patients is affected by subjective vertical position

    https://www.somasimple.com/forums/sh...ad.php?t=23891

    Abstract

    Purpose

    No method has been established to evaluate the dissociation between subjective and objective vertical positions with respect to the self-awareness of postural deformity in patients with Parkinson’s disease (PD). The purpose of this study was to demonstrate, from the relationship between an assessment of the dissociation of subjective and objective vertical positions of PD patients and an assessment based on established PD clinical evaluation scales, that the dissociation regarding vertical position is a factor in the severity of the forward flexion of trunk (FFT).

    Methods

    Subjects were 39 PD patients and 15 age-matched healthy individuals (control group). Posture was evaluated with measurement of FFT angle during static standing and the subjective vertical position (SV) of the patient. For evaluation of motor function, the Modified Hoehn & Yahr scale, Unified Parkinson’s Disease Rating Scale (UPDRS), 3-m Timed Up and Go Test (TUG), and Functional Reach Test (FRT) were used.

    Results

    In PD patients, FFT angle in the 3rd tertile of patients was 13.8±9.7°, significantly greater than those in the control group and the 1st and 2nd tertiles of PD patients (control group vs 3rd tertile, p = 0.008; 1st tertile vs 3rd tertile, p<0.001; 2nd vs 3rd tertile, p = 0.008). In multiple regression analysis for factors in the FFT angle, significant factors were SV, disease duration, and the standard deviation of each SV angle measurement.

    Conclusion

    The dissociation between SV and objective vertical position affects the FFT of PD patients, suggesting an involvement of non-basal ganglia pathologies.
    Update 11/07/2017
    Last edited by Jo Bowyer; 12-07-2017, 06:12 AM.

  • Jo Bowyer
    replied
    Neuronal Parkinson inclusions are different than expected

    https://www.sciencedaily.com/release...0626124941.htm

    An international team of researchers challenges the conventional understanding of the cause of Parkinson's disease. The researchers have shown that the inclusions in the brain's neurons, characteristic of Parkinson's disease, are comprised of a membranous medley rather than protein fibrils.

    Leave a comment:


  • Jo Bowyer
    replied
    Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease

    https://www.cell.com/neuron/fulltext...T+Newsletters=


    The Braak hypothesis posits that α-syn pathology can spread in a stereotyped fashion from the gastrointestinal tract via the vagus nerve to the ventral midbrain, where it selectively kills dopamine (DA) neurons of the substantia nigra pars compacta (SNc).

    Leave a comment:


  • Jo Bowyer
    replied
    The burden of care and the understanding of disease in Parkinson’s disease

    https://journals.plos.org/plosone/ar...l.pone.0217581

    Parkinson's disease (PD) is a neurodegenerative disease causing the loss of dopaminergic neurons in the substantia nigra, which chronically progresses [1]. Early PD patients undergoing medical treatment do not have significant difficulty in daily living, but patients with advanced PD experience difficulties in basic daily living activities due to various motor and non-motor symptoms, and the disability in daily living continually increases with progression of the disease [1,2]. Specific motor symptoms of PD, including bradykinesia, tremor, rigidity, and gait disturbance, are readily apparent to patients and caregivers, but their interests in and recognition of non-motor symptoms, including gastrointestinal symptoms, cognitive/emotional disorder, autonomic disturbance, and pain are lower [3]. In particular, the non-motor symptoms of PD have been identified as factors that increase burden of care and lower the quality of life more than the motor symptoms [4,5]. This finding has also been confirmed by a report showing that the non-motor symptoms may be the key factors that reduce the quality of life, even in early stages of the disease [6]. Therefore, proper understanding and recognition of the disease by PD patients and caregivers may be improved by providing more knowledge about the disease itself, and lack of understanding of the disease may have a negative effect on the care of PD patients [7,8].

    Leave a comment:


  • Jo Bowyer
    replied
    Impulse control disorders in Parkinson’s disease: A systematic review on the psychometric properties of the existing measures

    https://journals.plos.org/plosone/ar...l.pone.0217700

    A significant percentage of patients suffering from Parkinson’s Disease (PD) experience Impulse Control Disorders (ICDs), contributing to reduced quality of life. As they can be managed by reducing the dopamine dosage, the detection of their presence is crucial for PD treatment plan. Nevertheless, they tend to be under-recognized in clinical practice, since routine screening is not common–despite existing instruments that may support clinicians. This work presents a systematic review on the psychometric properties of instruments measuring ICDs in PD, to test whether clinicians dispose of valid tools that may help them in clinical assessment.

    Leave a comment:


  • Jo Bowyer
    replied
    Voluntary and spontaneous facial mimicry toward other’s emotional expression in patients with Parkinson’s disease

    https://journals.plos.org/plosone/ar...l.pone.0214957

    Leave a comment:


  • Jo Bowyer
    replied
    Virtual reality offers benefits for Parkinson's disease patients

    Training in virtual environment helps patients improve balance and avoid obstacles while walking

    https://www.sciencedaily.com/release...0409162815.htm

    Leave a comment:


  • Jo Bowyer
    replied
    Exercise can improve non-motor symptoms of Parkinson's disease

    https://www.sciencedaily.com/release...0304105418.htm

    Leave a comment:


  • Jo Bowyer
    replied
    New treatment offers potentially promising results for the possibility of slowing, stopping, or even reversing Parkinson's disease

    https://www.sciencedaily.com/release...0227081531.htm

    A pioneering clinical trials program that delivered an experimental treatment directly to the brain offers hope that it may be possible to restore the cells damaged in Parkinson's disease. The study investigated whether boosting the levels of a naturally-occurring growth factor, Glial Cell Line Derived Neurotrophic Factor (GDNF), can regenerate dying dopamine brain cells in patients with Parkinson's and reverse their condition, something no existing treatment can do. Potentially promising results of the third arm of the trials, an open-label extension study, are reported in the Journal of Parkinson's Disease.

    Leave a comment:


  • Jo Bowyer
    replied
    Altered brain activity patterns of Parkinson's captured in mice

    https://www.sciencedaily.com/release...0219132911.htm

    Parkinson's disrupts the basal ganglia, a set of nuclei that relays information from the wrinkled cortex to brain areas important for movement control. A nucleus known as the striatum acts as the primary input hub for the entire structure. Marked by a steep decline in the chemical messenger dopamine and cells that make it, Parkinson's robs the basal ganglia of the tools it needs to function properly and pushes the striatum into pathological hyperactivity.

    "When you take dopamine away, the cells reorganize, and that reorganization leads to most of the symptoms of Parkinson's," said Prof. Gordon Arbuthnott, senior author of the study and principal investigator of the OIST Brain Mechanism for Behaviour Unit. The research, published online on January 30, 2019 by the European Journal of Neuroscience, suggests that the striatal neurons' normal pattern of activity warps when the cells are starved of dopamine. The pattern becomes dominated by one particular subset of cells, often firing in sync.

    Leave a comment:


  • Jo Bowyer
    replied
    Can We Repair the Brain? Using Stem Cells to Treat Parkinson’s

    https://neurosciencenews.com/parkins...m-cells-10750/

    The most common PD treatment today is based on enhancing the activity of the nigro-striatal pathway in the brain with dopamine-modulating therapies, thereby increasing striatal dopamine levels and improving motor impairment associated with the disease. However, this treatment has significant long-term limitations and side effects. Stem cell technologies show promise for treating PD and may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come.

    Leave a comment:


  • Jo Bowyer
    replied
    The involvement of the gut in Parkinson's disease: hype or hope?

    https://www.sciencedaily.com/release...0207115006.htm

    Leave a comment:


  • Jo Bowyer
    replied
    Phase-Dependent Suppression of Beta Oscillations in Parkinson's Disease Patients

    http://www.jneurosci.org/content/39/6/1119.full

    Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (∼20 Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's disease patients.
    Obviously early days, but an interesting approach.

    Leave a comment:


  • Jo Bowyer
    replied
    The search for environmental causes of Parkinson's disease moves forward

    https://www.sciencedaily.com/release...0131125957.htm

    Leave a comment:


  • Jo Bowyer
    replied
    The Emerging Evidence of the Parkinson Pandemic

    https://content.iospress.com/article...ease/jpd181474



    For most of history, Parkinson disease was a rare disorder. In 1855, forty years after Dr. James Parkinson first described the condition, approximately 22 people of 15 million in England and Wales died of the condition [2]. In 2014, roughly 5,000 to 10,000 individuals of 65 million in the United Kingdom suffered the same fate [3]. In less than two centuries, a rare disorder became common.

    According to the Global Burden of Disease study, neurological disorders are currently the leading source of disability around the world, and the fastest growing of these disorders (in age-standardized rates of prevalence, disability, and deaths) is Parkinson disease [4].
    Though non-infectious, the Parkinson pandemic exhibits many of the characteristics of a pandemic [13]. Pandemics extend over large geographic areas, and Parkinson disease is increasing in every major region of the world [9]. Pandemics also tend to migrate, and the burden of Parkinson disease, while increasing everywhere, appears to be shifting in response to changes in aging and industrialization. Indeed, one study concluded that the burden, driven by demographic changes, would shift from the West to the East, especially China [14]. Like other pandemics, the Parkinson pandemic is experiencing exponential growth, and no one is immune to the condition.

    More generally, the Parkinson pandemic is similar to the pandemic of non-communicable diseases as articulated by Allen [15]. He argues that many chronic conditions (e.g., diabetes) that are now leading sources of death and disability in the world “are actually communicable conditions, and although the vectors of disease are nontraditional, the pandemic label is apt” [15]. Social, political, and economic trends are fueling the rise of many non-communicable conditions, and the “various ‘vectors of disease’ include ultraprocessed food and drink, alcohol, tobacco products, and wider social and environmental changes that limit physical activity” [15].


    The pandemic’s causes


    The Parkinson pandemic is fueled by aging populations, increasing longevity, declining smoking rates, and the by-products of industrialization. The incidence of Parkinson disease increases with age and rises sharply at around age 65 [16]. The world’s population is aging, as the number and proportion of individuals over 65 is rapidly increasing (Fig. 1). The combined result of these two factors is an unprecedented rise in the number of people with Parkinson disease.

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