Range Of Non-motor Symptoms Research Articles

Sex differences in Parkinson’s disease-related non motor symptoms: a focus on sleep problems

Parkinson’s disease (PD) symptomatology differs between females and males, yet the contribution of sex on sleep problems needs further analysis. Here, we aimed to investigate sex-specific patterns in the relationship between sleep problems, assessed using the Parkinson’s disease sleep scale (PDSS-2), non motor symptoms (NMS), measured by the NMS scale (NMSS), and health-related quality of life (HR-QoL), evaluated by the Parkinson’s disease questionnaire (PDQ-39), in a large cohort of PD patients. One-hundred-fifty-four PD patients were included in the study. Female PD patients (n = 62) exhibited a higher prevalence of sleep problems than males (n = 92), with nocturnal motor-related sleep issues being the most frequent. Sleep disturbances differently correlated with a range of NMS between the two sexes. In females, sleep problems mostly correlated with pain; on the other hand, sleep disturbances were linked to a frailer phenotype characterized by global dysautonomia, perception disturbances, and impaired cognitive function in males. Whether female PD patients experienced a lower HR-QoL than males, sleep disturbances were associated with a worse HR-QoL in both sexes. In conclusion, sleep problems in PD differently burden the two sexes, suggesting possible different etiopathogenesis, diagnostic investigations, and possibly tailored approaches.

Acupuncture Improves Sleep Disorders and Depression among Patients with Parkinson's Disease: A Meta-Analysis.

Parkinson's disease (PD) is associated with a range of non-motor symptoms that lack effective treatments. Acupuncture is a popular alternative therapy for PD patients that has been shown to improve motor symptoms. However, the efficacy of acupuncture in treating non-motor symptoms has remained controversial. The goal of our study was to systematically assess the existing evidence for acupuncture's efficacy in treating PD non-motor symptoms of sleep disorders, depression, anxiety, and fatigue. We conducted a meta-analysis of clinical trials by searching Pubmed, Embase, CINAHL, and Web of Science as electronic databases to evaluate acupuncture treatment for PD non-motor symptoms. Thirteen clinical trials met our inclusion criteria, and their methodological quality was assessed using the modified Jadad scale, indicating a moderate overall quality. Our results showed that acupuncture improved PD-related sleep disorders and depression but had no effect on anxiety and fatigue. Our meta-analysis suggests that acupuncture can be used as a complementary treatment for sleep disturbances and depression in PD patients and may exhibit a dual therapeutic effect on motor and non-motor symptoms. However, further well-designed clinical trials with larger sample sizes are needed to confirm these findings. Overall, our study highlights the potential of acupuncture as a viable complementary therapy for the treatment of PD non-motor symptoms of sleep disorders and depression, which can improve the quality of life of PD patients.

Effect of the Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulator Dipraglurant on Motor and Non-Motor Symptoms of Parkinson's Disease.

Parkinson's disease (PD) patients suffer not only from the primary motor symptoms of the disease but also from a range of non-motor symptoms (NMS) that cause disability and low quality of life. Excessive glutamate activity in the basal ganglia resulting from degeneration of the nigrostriatal dopamine pathway has been implicated in the motor symptoms, NMS and dyskinesias in PD patients. In this study, we investigated the effects of a selective mGlu5 negative allosteric modulator (NAM), dipraglurant, in a rodent motor symptoms model of PD, but also in models of anxiety, depression and obsessive-compulsive disorder, all of which are among the most prevalent NMS symptoms. Dipraglurant is rapidly absorbed after oral administration, readily crosses the blood-brain barrier, and exhibits a high correlation between plasma concentration and efficacy in behavioral models. In vivo, dipraglurant dose-dependently reduced haloperidol-induced catalepsy, increased punished licks in the Vogel conflict-drinking model, decreased immobility time in the forced swim test, decreased the number of buried marbles in the marble-burying test, but had no effect on rotarod performance or locomotor activity. These findings suggest that dipraglurant may have benefits to address some of the highly problematic comorbid non-motor symptoms of PD, in addition to its antidyskinetic effect demonstrated in PD-LID patients.

Insights into the roles of bacterial infection and antibiotics in Parkinson's disease.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, which is accompanied with the classical motor symptoms and a range of non-motor symptoms. Bacterial infection affects the neuroinflammation associated with the pathology of PD and various antibiotics have also been confirmed to play an important role not only in bacterial infection, but also in the PD progression. This mini-review summarized the role of common bacterial infection in PD and introduced several antibiotics that had anti-PD effects.

Parkinson's disease and Covid-19: Is there an impact of ethnicity and the need for palliative care.

Under the traditional models of care for People with Parkinson's Disease (PD, PwP), many of their needs remain unmet and a substantial burden of motor and non-motor symptoms they experience may not be tackled sufficiently. An introduction of palliative care (PC) interventions early in the course of PD offers profound benefits: it may improve quality of life of patients, their families and caregivers through the prevention and relief of medical symptoms, while, at the same time, emphasizing their emotional needs and spiritual wellbeing, establishing goals of care, and engaging in the advance care planning (ACP).The ongoing Coronavirus Disease 2019 (Covid-19) pandemic poses an unprecedented set of challenges for PwP and has in many ways (both directly and indirectly) magnified their suffering, thus rapidly raising the demand for PC interventions. Covid-19, as well as the repercussions of prolonged mobility restrictions and limited health-care access might exacerbate the severity of PD motor symptoms and interact negatively with a range of non-motor symptoms, with a detrimental effect on quality of life. Greater motor disability, higher amount of levodopa-induced motor fluctuations with an increased daily off-time, fatigue, anxiety, depression, sleep disturbances, pain and worsening of cognitive complaints might dominate the clinical presentation in PwP during the Covid-19 pandemic, alongside raising psychological and spiritual concerns and anticipatory grief.Here, we aim to provide a foundation for pragmatic and clinically orientated PC approach to improve quality of life and relieve suffering of PwP in the context of the current, ongoing Covid-19 pandemic.

Age-Stratified Risk of Dementia in Parkinson's Disease: A Nationwide, Population-Based, Retrospective Cohort Study in Taiwan.

Introduction: Parkinson's disease (PD) manifests with dominant motor symptoms and a wide range of non-motor symptoms (NMS). Dementia is one of the most disabling and exhausting NMS throughout the clinical course. We conducted a population-based, age-stratified, retrospective cohort study to investigate the incidence rate and risk of dementia of patients with newly diagnosed PD, and linked to the clinicopathological PD subtypes.Methods: Patients with newly diagnosed PD (PD group, n = 760) and control subjects (non-PD group, n = 3,034) were selected from the Taiwan's National Health Insurance Research Database from January 2001 to December 2005. The dementia incidence rate and dementia-free survival rate were calculated.Results: The overall dementia incidence rate was 17.5 and 5.7 per 1,000 person-years in PD and non-PD groups, respectively. The PD group had a significantly higher overall risk of dementia than controls (p < 0.001). The younger PD patients had a lower dementia incidence rate than the older PD patients, but a higher dementia risk compared to the same age of controls (<60 years, adjusted HR 6.55, 95% CI 1.56–27.48, p = 0.010). The dementia-free survival rate was significantly lower in the PD group compared to the non-PD group during follow-up (p < 0.001).Conclusion: In our study, the older age of onset in PD patients resulted in a higher incidence rate of dementia. In the young age of PD patients, the incidence rate of dementia was lower than the older PD patients, but the dementia risk was higher than controls of the same age. These findings possibly implied that there were different pathogenesis and pathologies causing dementia in younger and older PD patients.

Impulse control disorders in Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterised by typical motor symptoms and a range of non-motor symptoms, among which impulse control disorders, defined by an inability to resist temptations, impulses or urges, despite them being potentially harmful to the patient or caregivers, are gaining an increasing research interest. The most common compulsive activities include pathological gambling, hyper-sexuality, compulsive buying, and binge eating. The prevalence of impulse control disorders varies greatly depending on the country where the study was conducted, probably due to cultural and socioeconomic factors or the research methods used. Non-ergotamine dopamine agonists, and to a lesser extent highdose L-dopa and other antiparkinsonian drugs, are considered to be major risk factors for the development of impulse control disorders. Young age of patients, male gender, and early age of disease onset also increase the risk of developing this type of disorder. A probable cause of impulse control disorders is a state of dopaminergic overstimulation within the mesolimbic pathway and frontal-striatal circuit. The management of impulse control disorders is particularly challenging in view of the possible worsening of motor symptoms. The primary strategy remains dose reduction, discontinuation or switching from a dopamine agonist to another drug. If this type of intervention has failed, it is advisable to add atypical antipsychotics or antiepileptic drugs. Because of the low detection rate of impulse control disorders and their potentially devastating impact on patients’ personal and family lives, every clinician managing patients with Parkinson’s disease should be particularly vigilant for the presence of such disorders.

Немоторные проявления болезни Паркинсона

Currently, Parkinson's disease is an equally motor and non-motor disease with a wide range of non-motor symptoms. The article describes the non-motor symptoms of Parkinson's disease, assesses the severity and significance of these symptoms, as well as the possible influence on each other in terms of neurotransmitter dysfunction. A comparative characteristic of the results obtained with the data of international studies is carried out

Frontoparietal network resilience is associated with protection against cognitive decline in Parkinson\u2019s disease

Though Parkinson’s disease is primarily defined as a movement disorder, it is also characterized by a range of non-motor symptoms, including cognitive decline. The onset and progression of cognitive decline in individuals with Parkinson’s disease is variable, and the neurobiological mechanisms that contribute to, or protect against, cognitive decline in Parkinson’s disease are poorly understood. Using resting-state functional magnetic resonance imaging data collected from individuals with Parkinson’s disease with and without cognitive decline, we examined the relationship between topological brain-network resilience and cognition in Parkinson’s disease. By leveraging network attack analyses, we demonstrate that relative to individuals with Parkinson’s disease experiencing cognitive decline, the frontoparietal network in cognitively stable individuals with Parkinson’s disease is significantly more resilient to network perturbation. Our findings suggest that the topological robustness of the frontoparietal network is associated with the absence of cognitive decline in individuals with Parkinson’s disease.

Abnormally reduced frontal cortex activity during Trail-Making-Test in prodromal parkinson's disease–a fNIRS study

Parkinson's Disease (PD) is a neurodegenerative disorder leading to typical motor as well as a range of non-motor symptoms, including cognitive decline mainly characterized by executive deficits. The latter are known to appear years before the typical motor signs, thus representing the prodromal phase of PD. However, appropriate methods for measuring executive dysfunction in this context are not well established yet. Traditionally, executive performance is associated with frontal structures. Here, we investigated prodromal, early PD patients and healthy controls regarding their executive functioning on the behavioral and neural level, measured by the Trail-Making-Test (TMT) combined with functional near-infrared spectroscopy. We observed significantly reduced neural activity in the right dorsolateral prefrontal cortex within PD patients compared to controls completing the TMT-A and -B in contrast to the TMT-C, but no differences on a behavioral level. These promising results need to be confirmed and checked for reliability in future studies to extend the spectrum of markers applied in prodromal PD.

Non-Motor Symptoms of Amyotrophic Lateral Sclerosis: A Multi-Faceted Disorder.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor pathways. A growing body of evidence from recent years suggests that ALS results in a wide range of non-motor symptoms as well, which can have a significant impact on patients' quality of life. These symptoms could also, in turn, provide useful information as biomarkers for disease progression, and can shed insight on ALS mechanisms. Here we aim to review a wide range of non-motor symptoms of ALS, with emphasis on their importance to research and clinical treatment of patients.

Prioritising target non-pharmacological interventions for research in Parkinson\u2019s disease: achieving consensus from key stakeholders

BackgroundIn 2014 Parkinson’s UK conducted a research prioritisation exercise with stakeholders highlighting important clinical research questions. The exercise highlighted the need for effective interventions to be developed and tested to tackle a range of non-motor symptoms including: sleep quality, stress and anxiety, mild cognitive impairment, dementia and urinary problems. The present work set out to build on this exercise by prioritising types of non-pharmacological interventions to be tested to treat the identified non-motor symptoms.MethodsA Patient and Public Involvement exercise was used to reach consensus on intervention priorities for the treatment of non-motor symptoms. A Delphi structure was used to support the feedback collected. A first-round prioritisation survey was conducted followed by a panel discussion. Nineteen panellists completed the first-round survey (9 people with Parkinson’s and 10 professionals working in Parkinson’s) and 16 participated in the panel discussion (8 people with Parkinson’s and 8 professionals working in Parkinson’s). A second-round prioritization survey was conducted after the panel discussion with 13 people with Parkinson’s.ResultsPhysical activity, third wave cognitive therapies and cognitive training were rated as priority interventions for the treatment of a range of non-motor symptoms. There was broad agreement on intervention priorities between health care professionals and people with Parkinson’s. A consensus was reached that research should focus on therapies which could be used to treat several different non-motor symptoms. In the context of increasing digitisation, the need for human interaction as an intervention component was highlighted.ConclusionBringing together Parkinson’s professionals and people with Parkinson’s resulted in a final treatment priority list which should be both feasible to carry out in routine clinical practice and acceptable to both professionals and people with Parkinson’s. The workshop further specified research priorities in Parkinson’s disease based on the current evidence base, stakeholder preferences, and feasibility. Research should focus on developing and testing non-pharmacological treatments which could be effective across a range of symptoms but specifically focusing on tailored physical activity interventions, cognitive therapies and cognitive training.

Clinical Perspectives of Parkinson's Disease for Ophthalmologists, Otorhinolaryngologists, Cardiologists, Dentists, Gastroenterologists, Urologists, Physiatrists, and Psychiatrists.

Parkinson's disease (PD) is a multisystemic disorder characterized by various non-motor symptoms (NMS) in addition to motor dysfunction. NMS include sleep, ocular, olfactory, throat, cardiovascular, gastrointestinal, genitourinary, or musculoskeletal disorders. A range of NMS, particularly hyposmia, sleep disturbances, constipation, and depression, can even appear prior to the motor symptoms of PD. Because NMS can affect multiple organs and result in major disabilities, the recognition and multidisciplinary and collaborative management of NMS by physicians is essential for patients with PD. Therefore, the aim of this review article is to provide an overview of the organs that are affected by NMS in PD together with a brief review of pathophysiology and treatment options.

NON-MOTOR SYMPTOMS AND QUALITY OF LIFE IN PATIENTS WITH ESSENTIAL TREMOR, PARKINSONS DISEASE AND THE COMBINATION OF ESSENTIAL TREMOR AND PARKINSONS DISEASE

Aim of the study: to assess non-motor symptoms and quality of life in patients with essential tremor (ET), different stages of Parkinson’s Disease (PD) and combination of ET and PD (ET-PD). Materials and methods of the research: We examined 82 patients with ET, 20 patients with ET-PD, 283 patients with PD, and 72 neurologically healthy volunteers. The neuropsychological status, intensity of motor symptoms, the grade of vegetative dysfunction and dyssomnia, and quality of life of patients were assessed. Results: Patients with ET showed wide range of nonmotor symptoms. The severity of cognitive impairment in group of patients with ET corresponded with the same severity of patients with early stages of PD. It is interesting that patients with ET showed more severe depression than patients with early stages of PD. The maximum severity of anxiety-depressive disorders was observed in patients with the combination of ET-PD. Conclusion: In spite of the fact that it is usual to consider the ET as a monosymptomatic benign disease, we have found significant non-motor disorders in this group of patients and a significant violation of the quality of life. The results of the study also give evidence that patients with ET-PD represent a special group of patients, characterized by special, both motor and non-motor symptoms. The data we obtained made it possible to form a deeper understanding of the generality of the clinical manifestations of ET, PD and ET-PD, which will make it possible to improve the quality of management of patients with these nosologies in clinical practice.

Sleep disturbances in patients with Parkinson’s disease: It’s time to wake up!

Patients with Parkinson’s disease (PD) develop a range of non-motor symptoms (NMS). Sleep disturbance is one of the common NMS of PD and the onset of sleep disorders often precede the onset of motor symptoms of PD. Motor symptoms of PD often receive the main clinical focus and the sleep disturbances often go unnoticed in clinical practice. Given that the prevalence of PD is higher in the elderly population, primary care physicians, geriatricians, and gerontologists are usually the first point of contact for a majority of patients with PD. Because of this, it is important that they have a clear understanding about the diagnosis and management of the sleep disturbances in PD. This review provides an overview of the full spectrum of sleep disturbances in PD that includes insomnia, excessive daytime sleepiness, rapid eye movement sleep behavior disorder, restless leg syndrome, periodic limb movements, and obstructive sleep apnea. Although these sleep disorders may be primarily associated with PD, it is crucial to delineate the other treatable causes of sleep disturbances such as side effects of medications and physical symptoms not related to PD. This review highlights the major sleep disorders observed in patients with PD and succinctly discusses their management aspects. In addition, we have briefly described the effect of deep brain stimulation on the natural course of several sleep disorders in PD in this article.

Nonmotor Effects of Conventional and Transdermal Dopaminergic Therapies in Parkinson's Disease.

Nonmotor symptoms (NMS) are an integral component of Parkinson's disease (PD). Because the burden and range of NMS are key determinants of quality of life for patients and caregivers, their management is a crucial issue in clinical practice. Although a range of NMS have a dopaminergic pathophysiological basis, this fact is underrecognized, and thus, they are often regarded as dopamine unresponsive symptoms. However, substantial evidence indicates that many NMS respond to oral and transdermal dopaminergic therapies. In contrast, certain NMS are exacerbated or even precipitated by dopaminergic drugs and these unwanted effects may be seriously dangerous. Therefore, a dopaminergic strategy for NMS should be based on a consideration of the benefits vs the risks in individual patients with PD.

The Nonmotor Features of Parkinson's Disease.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) were recognized by the great James Parkinson himself who mentioned symptoms such as sleep dysfunction, delirium, dementia, and dysautonomia, in his seminal 1817 essay, "An Essay on the Shaking Palsy" (Parkinson, 1817). In spite of the key impact of PD NMS on quality of life, there was little holistic research and awareness till the validation and use of comprehensive tools such as the NMS questionnaire, scale, and the revised version of the unified PD rating scale. Research studies using these tools highlighted the key impact of the burden of NMS on quality of life of PD patients and the need for NMS to be routinely assessed in clinic. We now define PD as a motor and nonmotor disorder, and the natural history includes a long prodromal phase of PD dominated by a range of NMS. The prodromal phase is the subject of much research particularly in relation to neuroprotection and identifying subjects at risk. Use of NMS tools has also validated burden grading of NMS with cutoff values, which can be used as outcome measure in clinical trials. Finally, the complex multineurotransmitter dysfunction that is seen in PD has been shown to manifest clinically as nonmotor subtypes. Recognition of such subtypes is likely to lead to the emergence of personalized and precision medicine in PD.

Multimodal Imaging Signatures of Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers. We present a statistical framework for analyzing neuroimaging data from multiple modalities to determine features that reliably distinguish PD patients from healthy control (HC) subjects. Our approach builds on elastic net, performing regularization and variable selection, while introducing additional criteria centering on parsimony and reproducibility. We apply our method to data from 42 subjects (28 PD patients and 14 HC). Our approach demonstrates extremely high accuracy, assessed via cross-validation, and isolates brain regions that are implicated in the neurodegenerative PD process.

Neurorehabilitation in Parkinson's disease

Parkinson's disease (PD) is a chronic neurodegenerative disease which is characterized by the cardinal symptoms akinesia, rigidity, rest tremor and postural instability. Besides PD features also a wide range of non-motor symptoms. Physical activity is recommended for all stages of PD and may hypothetically even have a positive influence on the course of the disease. Rehabilitative treatments become increasingly important in the advanced stage of the disease and include mainly physiotherapy, occupational therapy and speech therapy. Neurorehabilitation is arguably most important for the treatment of axial symptoms such as freezing, hypophonia, dysphagia, postural instability and postural disturbances that respond poorly to drug therapy. This article provides an overview of current developments in the field of neurorehabilitation in PD.

The range and nature of non-motor symptoms in drug-naive Parkinson's disease patients: a state-of-the-art systematic review.

Non-motor symptoms (NMS) are a key component of Parkinson’s disease (PD). A range of NMS, most notably impaired sense of smell, sleep dysfunction, and dysautonomia are present from the ‘pre-motor’ phase to the final palliative stage. Theories as to the pathogenesis of PD such as those proposed by Braak and others also support the occurrence of NMS in PD years before motor symptoms start. However, research addressing the range and nature of NMS in PD has been confounded by the fact that many NMS arise as part of drug-related side effects. Thus, drug-naive PD (DNPD) patients provide an ideal population to study the differences in the presentation of NMS. The aim of this paper is therefore to systematically review all the available studies of NMS in DNPD patients. We believe this is the first review of its kind. The current review confirms the increasing research being conducted into NMS in DNPD patients as well as the necessity for further investigation into less-studied NMS, such as pain. Moreover, the data confirms non-motor heterogeneity among PD patients, and, therefore, further research into the concept of non-motor subtyping is encouraged. The review suggests that the clinical assessment of NMS should be integral to any assessment of PD in clinical and research settings.