scholarly journals Importance of the Brain Angiotensin System in Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
John W. Wright ◽  
Joseph W. Harding
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Oral Delivery ◽  
Sleep Disturbances ◽  
Treatment Strategies ◽  
Disease Process ◽  
Motor Dysfunction ◽  
Receptor System ◽  
Major Health Problem

Parkinson’s disease (PD) has become a major health problem affecting 1.5% of the world’s population over 65 years of age. As life expectancy has increased so has the occurrence of PD. The primary direct consequence of this disease is the loss of dopaminergic (DA) neurons in the substantia nigra and striatum. As the intensity of motor dysfunction increases, the symptomatic triad of bradykinesia, tremors-at-rest, and rigidity occur. Progressive neurodegeneration may also impact non-DA neurotransmitter systems including cholinergic, noradrenergic, and serotonergic, often leading to the development of depression, sleep disturbances, dementia, and autonomic nervous system failure. L-DOPA is the most efficacious oral delivery treatment for controlling motor symptoms; however, this approach is ineffective regarding nonmotor symptoms. New treatment strategies are needed designed to provide neuroprotection and encourage neurogenesis and synaptogenesis to slow or reverse this disease process. The hepatocyte growth factor (HGF)/c-Met receptor system is a member of the growth factor family and has been shown to protect against degeneration of DA neurons in animal models. Recently, small angiotensin-based blood-brain barrier penetrant mimetics have been developed that activate this HGF/c-Met system. These compounds may offer a new and novel approach to the treatment of Parkinson’s disease.

scholarly journals Impact of Impulse Control Disorders on Sleep-Wake Regulation in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Atbin Djamshidian ◽  
Werner Poewe ◽  
Birgit Högl
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impulse Control ◽  
Sleep Disturbances ◽  
Treatment Strategies ◽  
Compulsive Buying ◽  
Impulse Control Disorders ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Behavioural Addictions

Sleep disturbances are common in patients with Parkinson’s disease (PD) and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered.

scholarly journals New awakenings: current understanding of sleep dysfunction and its treatment in Parkinson’s disease

2019 ◽  
Vol 267 (1) ◽  
pp. 288-294 ◽  
Author(s):  
Lindsay H. M. Keir ◽  
David P. Breen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disorders ◽  
Sleep Disturbances ◽  
Disease Process ◽  
Underlying Disease ◽  
Prodromal Phase ◽  
Waste Products ◽  
New Treatment

AbstractThe non-motor features of Parkinson’s disease (PD) are increasingly being recognised. This review deals with the spectrum of sleep disorders associated with PD, which have a multifactorial aetiology and can significantly have an impact on the quality of life of patients and their carers. Some sleep disorders represent a prodromal phase of PD, with REM sleep behaviour disorder (RBD) being of particular interest in this regard, whereas others become more common as the disease advances. Understanding the pathophysiology of these sleep disturbances will hopefully lead to new treatment opportunities in the future. The recent discovery of the glymphatic system for removal of waste products from the brain has also raised the possibility that sleep disruption may cause or accelerate the underlying disease process.

scholarly journals Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Francesca Magrinelli ◽  
Alessandro Picelli ◽  
Pierluigi Tocco ◽  
Angela Federico ◽  
Laura Roncari ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Signs And Symptoms ◽  
Motor Fluctuations ◽  
Motor Dysfunction ◽  
Nonmotor Symptoms ◽  
Motor Problems ◽  
Gait Disturbances ◽  
Symptoms And Signs

Cardinal motor features of Parkinson’s disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Parkinson’s Disease Motor Symptom Progression Slowed with Multisensory Dance Learning over 3-Years: A Preliminary Longitudinal Investigation

2021 ◽  
Vol 11 (7) ◽  
pp. 895
Author(s):  
Karolina A. Bearss ◽  
Joseph F. X. DeSouza
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Daily Living ◽  
Rating Scale ◽  
Motor Impairment ◽  
Motor Dysfunction ◽  
Motor Symptom ◽  
Significant Group ◽  
Rate Of Decline ◽  
Symptom Progression

Parkinson’s disease (PD) is a neurodegenerative disease that has a fast progression of motor dysfunction within the first 5 years of diagnosis, showing an annual motor rate of decline of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between 5.2 and 8.9 points. We aimed to determine both motor and non-motor PD symptom progression while participating in dance classes once per week over a period of three years. Longitudinal data was assessed for a total of 32 people with PD using MDS-UPDRS scores. Daily motor rate of decline was zero (slope = 0.000146) in PD-Dancers, indicating no motor impairment, whereas the PD-Reference group showed the expected motor decline across three years (p < 0.01). Similarly, non-motor aspects of daily living, motor experiences of daily living, and motor complications showed no significant decline. A significant group (PD-Dancers and PD-Reference) by days interaction showed that PD who train once per week have less motor impairment (M = 18.75) than PD-References who do not train (M = 24.61) over time (p < 0.05). Training is effective at slowing both motor and non-motor PD symptoms over three years as shown in decreased scores of the MDS-UPDRS.

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

2021 ◽  
pp. 1-11
Author(s):  
Valentina Leta ◽  
Daniele Urso ◽  
Lucia Batzu ◽  
Daniel Weintraub ◽  
Nataliya Titova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
De Novo ◽  
Motor Dysfunction ◽  
Group Differences ◽  
Motor Symptoms ◽  
Kaplan Meier ◽  
Patients At Risk ◽  
Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p <  0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p <  0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

scholarly journals Prognostic predictors relevant to end-of-life palliative care in Parkinson’s disease and related disorders: a systematic review

2021 ◽  
pp. jnnp-2020-323939
Author(s):  
Umer Akbar ◽  
Robert Brett McQueen ◽  
Julienne Bemski ◽  
Julie Carter ◽  
Elizabeth R Goy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Palliative Care ◽  
Parkinson's Disease ◽  
End Of Life ◽  
Cause Of Death ◽  
Quantitative Research ◽  
Motor Dysfunction ◽  
Clinical Markers ◽  
Hospice Referral ◽  
Survey Responses

Parkinson’s disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970–2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson’s Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.

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