Wide Range Of Non-motor Symptoms Research Articles

Mixed anxiety-depressive disorder in Parkinson's disease associated with worse resting state functional response to deep brain stimulation of subthalamic nucleus

BackgroundParkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). ObjectivesThe aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. MethodsResting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. ResultsWhile all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. ConclusionsSTN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

The Genetic Landscape of Sleep Disorders in Parkinson's Disease.

Parknson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD is characterized by a wide range of motor symptoms, however the clinical spectrum of PD covers a wide range of non-motor symptoms, as well. Sleep disorders are among the most common non-motor symptoms of PD, can occur at any stage of the disease and significantly affect quality of life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA) and circadian rhythm disturbances. One of the main challenges in PD research is identifying individuals during the prodromal phase of the disease. Combining genetic and prodromal data may aid the early identification of individuals susceptible to PD. This review highlights current data regarding the genetic component of sleep disorders in PD patients, focusing on genes that have currently been associated with this PD co-morbidity.

Associations of serum neuromarkers with clinical features of Parkinson's disease

To evaluate the clinical and laboratory correlation of biomarkers with anti- and pro-apoptotic activity with the severity of motor and non-motor symptoms depending on the progression rate of Parkinson's disease (PD). A wide range of non-motor symptoms (emotional-affective, cognitive, psychotic and behavioral disorders, fatigue, sleep disorders and autonomic disorders) was evaluated using validated scales and a number of serum neuromarkers responsible for neuroplasticity and neuronal survival processes (BDNF, PDGF, cathepsin D) in 71 patients with PD (mean age 65 (55; 70) years, disease duration 7 (4; 9) years, age of onset 57 (49; 62) years). The concentration of biomarkers (BDNF, PDGF and cathepsin D) was the lowest in the group of patients with a rapid PD progression rate (p<0.001, p=0.001 and p=0.031, respectively), the severity of motor and most non-motor symptoms was higher (p=0.023 and p=0.001, respectively) compared to middle and slow progression rate. There were correlations between BDNF concentration and the severity of depression (r=-0.63, p<0.001), apathy (r=-0.48, p<0.001), impulsive behavioral disorders (r=0.500, p<0.001), level of cognitive functions (r=0.54, p<0.001), motor symptoms (r=-0.43, p<0.001); between PDGF level and the severity of motor manifestations of PD (r=-0.30, p=0.011), depression (r=-0.70, p<0.001), apathy (r=-0.460, p<0.001), the degree of severity of behavioral disorders (r=0.742, p<0.001). No significant correlations were observed between the level of cathepsin D and the severity of clinical manifestations of PD, which indicates the connection of cathepsin D with the general pathogenesis of PD. The possibility of using serum proteins of the neurotrophin subfamily and the protein associated with autophagy, cathepsin D, as biomarkers that determine the prognosis of PD, is considered.

Emerging Role of Long Noncoding RNAs in Regulating Inflammasome-Mediated Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD) is one of the complex neurodegenerative disorders, primarily characterized by motor deficits, including bradykinesia, tremor, rigidity, and postural instability. The underlying pathophysiology involves the progressive loss of dopaminergic neurons within the substantia nigra pars compacta, leading to dopamine depletion in the basal ganglia circuitry. While motor symptoms are hallmark features of PD, emerging research highlights a wide range of non-motor symptoms, including cognitive impairments, mood disturbances, and autonomic dysfunctions. Inflammasome activation is pivotal in inducing neuroinflammation and promoting disease onset, progression, and severity of PD. Several studies have shown that long noncoding RNAs (lncRNAs) modulate inflammasomes in the pathogenesis of neurodegenerative diseases. Dysregulation of lncRNAs is linked to aberrant gene expression and cellular processes in neurodegeneration, causing the activation of inflammasomes that contribute to neuroinflammation and neurodegeneration. Inflammasomes are cytosolic proteins that form complexes upon activation, inducing inflammation and neuronal cell death. This review explores the significance of lncRNAs in regulating inflammasomes in PD, primarily focusing on specific lncRNAs such as nuclear paraspeckle assembly transcript 1 (NEATNEAT1), X-inactive specific transcript (XIST), growth arrest-specific 5 (GAS5), and HOX transcript antisense RNA (HOTAIR), which have been shown to activate or inhibit the NLRP3 inflammasome and induce the release of proinflammatory cytokines. Moreover, some lncRNAs mediate inflammasome activation through miRNA interactions. Understanding the roles of lncRNAs in inflammasome regulation provides new therapeutic targets for controlling neuroinflammation and reducing the progression of neurodegeneration. Identifying lncRNA-mediated regulatory pathways paves the way for novel therapies in the battle against these devastating neurodegenerative disorders.

Therapeutic Approaches to Non-Motor Symptoms of Parkinson's Disease: A Current Update on Preclinical Evidence.

Despite being classified as a movement disorder, Parkinson's disease (PD) is characterized by a wide range of non-motor symptoms that significantly affect the patients' quality of life. However, clear evidence-based therapy recommendations for non-motor symptoms of PD are uncommon. Animal models of PD have previously been shown to be useful for advancing the knowledge and treatment of motor symptoms. However, these models may provide insight into and assess therapies for non-motor symptoms in PD. This paper highlights non-motor symptoms in preclinical models of PD and the current position regarding preclinical therapeutic approaches for these non-motor symptoms. This information may be relevant for designing future preclinical investigations of therapies for nonmotor symptoms in PD.

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.

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

Decreased emotional creativity and its relationship with cognitive functions in Parkinson’s disease: A preliminary study

Patients with Parkinson’s disease (PD) suffer from a wide range of non-motor symptoms, including cognitive deficits and impairment of emotional processing. The present study aimed to explore in PD patients compared to healthy adults the relationship between cognitive performance and emotional creativity (EC), defined as a set of cognitive abilities and personality traits related to originality and appropriateness of emotional experience. PD patients (n = 22) and healthy controls (n = 40) underwent a complex neuropsychological assessment and were administrated with the self-reported Emotional Creativity Inventory (ECI) questionnaire. To explore the relationship between cognitive tests and the ECI, a regression analysis was conducted. PD patients and healthy controls differed significantly in the EC component Preparedness as well as in the neuropsychological test battery scores. PD patients showed lower scores in cognitive tests and a lower score in Preparedness compared to healthy adults. The output of the regression analysis showed that the extent to which the neuropsychological tests relate to the ECI components is low.

Rotigotine Transdermal Patch for Motor and Non-motor Parkinson's Disease: A Review of 12 Years' Clinical Experience.

Motor and non-motor symptoms (NMS) have a substantial effect on the health-related quality of life (QoL) of patients with Parkinson's disease (PD). Transdermal therapy has emerged as a time-tested practical treatment option, and the rotigotine patch has been used worldwide as an alternative to conventional oral treatment for PD. The efficacy of rotigotine on motor aspects of PD, as well as its safety and tolerability profile, are well-established, whereas its effects on a wide range of NMS have been described and studied but are not widely appreciated. In this review, we present our overall experience with rotigotine and its tolerability and make recommendations for its use in PD and restless legs syndrome, with a specific focus on NMS, underpinned by level 1–4 evidence. We believe that the effective use of the rotigotine transdermal patch can address motor symptoms and a wide range of NMS, improving health-related QoL for patients with PD. More specifically, the positive effects of rotigotine on non-motor fluctuations are also relevant. We also discuss the additional advantages of the transdermal application of rotigotine when oral therapy cannot be used, for instance in acute medical emergencies or nil-by-mouth or pre/post-surgical scenarios. We highlight evidence to support the use of rotigotine in selected cases (in addition to general use for motor benefit) in the context of personalised medicine.

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.

Association of -94 ATTG insertion/deletion NFkB1 and c.*126G>A NFkBIA genetic polymorphisms with oxidative and nitrosative stress biomarkers in Brazilian subjects with Parkinson’s Disease

Parkinson's disease (PD) is a complex neurodegenerative disorder, resulting dopaminergic neuronal cell death in the substantia nigra. The disease is characterized by major motor impairment, being bradykinesia, rest tremor, rigidity and loss of postural reflexes the most common, while autonomic dysfunctions, sleep disturbances and psychiatric disorders are some of the wide range of non-motor symptoms. Several processes have been identified to be associated with disease development, such as mitochondrial dysfunction, oxidative/nitrosative stress and neuroinflammation. NF-κB is an important transcription factor that regulates several inflammatory elements and pathways, and polymorphisms on NFKB1 and NFKBIA genes can potentially influence redox balance towards a pro-oxidative frame, modulating disease progression. Evaluation of these polymorphisms in the redox status of PD subjects could provide new insights on the pathogenesis of this disorder. The study aimed to test associations of -94 in./del ATTG NFKB1 (rs28362491) and c.*126G > A NFKBIA (rs696) polymorphisms with PD development, and to test the influence of both polymorphisms on oxidative/nitrosative stress (OS/NS) parameters. A total of 110 Brazilian individuals were enrolled, being 55 subjects recruited from University Hospital of Londrina as the PD group, and 55 subjects matched for age, sex and ethnicity composed the healthy control (HC) group. NFkB1 and NFkBIA polymorphisms were genotyped by PCR-RFLP. Lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), sulfhydryl groups (SH), total radical trapping antioxidant parameter (TRAP) and paraoxonase-1 activity (PON-1) were assessed. Despite no association of polymorphisms on disease development was observed, in PD subjects the NFKB1 del/del genotype was associated with higher levels of LOOH, while NFkBIA GA and AA genotypes were associated with higher NOx levels, suggesting that NFkB plays a role in PD susceptbility. In conclusion, the prospect of genetic polymorphisms of elements involved in inflammation and OS/NS might be a new approach to unravel PD etiology.

A Pragmatic Approach to the Perioperative Management of Parkinson's Disease.

Patients with Parkinson's disease (PD) may undergo several elective and emergency surgeries. Motor fluctuations, the presence of a wide range of non-motor symptoms (NMS), and the use of several medications, often not limited to dopaminergic agents, make the perioperative management of PD challenging. However, the literature on perioperative management of PD is sparse. In this descriptive review article, we comprehensively discuss the issues in the pre-, intra-, and postoperative phases which may negatively affect the PD patients and discuss the approach to their prevention and management. The major preoperative challenges include accurate medication reconciliation and administration of the dopaminergic medications during the nil per os (NPO) state. While the former can be addressed with staff education and PD-specific admission protocols, knowledge of non-oral formulations of dopaminergic agents (apomorphine, inhalational levodopa, and rotigotine transdermal patch) is the key to the management of the Parkinsonian symptoms in NPO state. Deep brain stimulation (DBS) devices should be turned off to avert potential electromagnetic interference with surgical appliances. Choosing the appropriate anesthesia and avoiding and managing respiratory issues and dysautonomia are the major intraoperative challenges. Timely reinitiation of dopaminergic medications, adequate management of pain, nausea, and vomiting, and prevention of postoperative infections and delirium are the postoperative challenges. Overall, a multidisciplinary approach is pivotal to prevent and manage the perioperative complications in PD. Administration of anti-Parkinson medications during NPO state, prevention of anesthesia-related complications, and timely rehabilitation remain the key to healthy surgical outcomes.

Animal Model for Lower Urinary Tract Dysfunction in Parkinson's Disease.

Although Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, various non-motor symptoms often precede these other symptoms. While motor symptoms are certainly burdensome, a wide range of non-motor symptoms have emerged as the key determinant of the quality of life in PD patients. The prevalence of lower urinary tract symptoms differs according to the study, with ranges between 27% and 63.9%. These can be influenced by the stage of disease, the presence of lower urinary tract-related comorbidities, and parallels with other manifestations of autonomic dysfunction. Animal models can provide a platform for investigating the mechanisms of PD-related dysfunction and for the assessment of novel treatment strategies. Animal research efforts have been primarily focused on PD motor signs and symptoms. However, the etiology of lower urinary tract dysfunction in PD has yet to be definitively clarified. Several animal PD models are available, each of which has a different effect on the autonomic nervous system. In this article, we review the various lower urinary tract dysfunction animal PD models. We additionally discuss techniques for determining the appropriate model for evaluating the development of lower urinary tract dysfunction treatments.

Frequency and Dynamics of Non-motor Symptoms Presentation in Hispanic Patients With Parkinson Disease.

The clinical phenotype of Parkinson's disease (PD) encompasses a wide range of non-motor symptoms (NMS) compromising the quality of life of affected patients. Currently, information about NMS in PD is scarce among Hispanic populations. Furthermore, few studies have reported the temporal pattern of NMS presentation. We conducted a cross-sectional study aimed to describe the frequency and time of NMS occurrence in Hispanic patients with PD using the self-completed NMS questionnaire (NMSQuest). Participants were interrogated about the time of each NMS presentation respect to the onset of motor symptoms. The frequency of NMS was described according to gender, age at disease onset, disease duration and Hoehn and Yahr (H&Y) stage. We enrolled 120 patients, 73.33% males and 26.66% females, with a mean age of 63.33 ± 8.60 years. All the participants presented at least 1 NMS. The median number of NMS per patient was 12. The most frequent NMS domains were miscellaneous, urinary tract, sleep/fatigue, and gastrointestinal tract symptoms, with no significant gender differences. The most frequent individual NMS were nocturia, urinary urgency, feeling sadness, and constipation. Any patient reported NMS before the onset of motor manifestations. The pattern of occurrence of NMS domains in our population was as follows: attention/memory, cardiovascular, gastrointestinal tract, perceptual problems/hallucinations, mood/cognition, urinary, miscellaneous, sleep/fatigue, and sexual function. Nausea/vomiting was the earliest symptom observed in all patients, whereas sexual dysfunction and changes in interest for sex were the last symptoms to occur. We found no differences in the total number and frequency of NMS between participants grouped according to their age at disease onset. Conversely, patients with a duration of disease >10 years reported a higher frequency of NMS compared to participants with a duration of disease < 10 years. The total number of NMS per patient increased as the HY stage progressed. The proportion of patients presenting symptoms of the gastrointestinal tract, urinary tract, mood/cognition, cardiovascular, and sexual function domains was higher in the HY 4–5 group. Our study provides relevant data to improve our understanding of NMS in PD, which may contribute to anticipate and plan diagnostic and therapeutic strategies among Hispanic PD patients.

Motor and Nonmotor Symptoms of Parkinson's Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?

Lewy body diseases, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.

Tetracycline repurposing in neurodegeneration: focus on Parkinson's disease.

The prevalence of Parkinson's disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds. This strategy has revealed that tetracyclines are promising candidates for the treatment of Parkinson's disease. Tetracyclines, which are neuroprotective, inhibit proinflammatory molecule production, matrix metalloproteinase activity, mitochondrial dysfunction, protein misfolding/aggregation, and microglial activation. Two commonly used semisynthetic second-generation tetracycline derivatives, minocycline and doxycycline, exhibit effective neuroprotective activity in experimental models of neurodegenerative/ neuropsychiatric diseases and no substantial toxicity. Moreover, novel synthetic tetracyclines with different biological properties due to chemical tuning are now available. In this review, we discuss the multiple effects and clinical properties of tetracyclines and their potential use in Parkinson's disease treatment. In addition, we examine the hypothesis that the anti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles in humans from their use for over 50years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic, to treat Parkinson's disease.

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.

Interaction of amyloidogenic proteins in pancreatic β cells from subjects with synucleinopathies.

Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination. We examined the pancreatic accumulation of phosphorylated α-synuclein and of the islet amyloid polypeptide precursor (IAPP), an amyloidogenic protein that plays an unknown role in diabetes mellitus, but that can promote α-synuclein amyloid deposition in vitro. Moreover, we performed proximity ligation assays to assess whether these two proteins interact in the pancreas of these subjects. Cytoplasmic phosphorylated α-synuclein deposits were found in the pancreatic β cells of 14 subjects with Parkinson's disease (93%), in 11 subjects with Lewy body Dementia (85%) and in 8 subjects with incidental Lewy body disease (73%). Furthermore, we found similar phosphorylated α-synuclein inclusions in 23 subjects with a normal neuropathological examination but with diabetes mellitus (68%) and in 9 control subjects (17%). In addition, IAPP/α-synuclein interactions appear to occur in patients with pancreatic inclusions of phosphorylated α-synuclein. The presence of phosphorylated α-synuclein inclusions in pancreatic β cells provides a new evidence of a mechanism that is potentially common to the pathogenesis of diabetes mellitus, PD and DLB. Moreover, the interaction of IAPP and α-synuclein in the pancreatic β cells of patients may represent a novel target for the development of strategies to treat these diseases.

Clinical Efficacy of Istradefylline for Depression in Parkinson’s Disease

Background: Parkinson’s disease (PD) is a common movement disorder with a wide range of non-motor symptoms. Depression is one of these symptoms; however, its pathomechanism and management remains to be elucidated. We evaluated of istradefylline (ISD), a first selective adenosine A2A receptor antagonist, for the treatment of depression in PD. Method: This was an open-labeled, prospective study that enrolled 15 PD patients (Men 8, Women 7) with motor fluctuations who fully filled UK PD society brain bank clinical diagnostic criteria. We added ISD 20 mg/day for 4 weeks followed with 40 mg/day for next 4 weeks on the preceding anti-parkinsonian medications. We evaluated Patient Health Questionnaire (PHQ-9) and Unified PD Rating Scale (UPDRS) part III (on state) at baseline and 8 weeks follow-up. Results: 14 patients completed the evaluations. PHQ-9 scores improved in 5 patients (responder). PHQ-9 scores of responders at baseline were higher than those of nonresponders; however, there was no significant difference. Furthermore, there were no significant differences in UPDRS part III, age, onset, duration, daily levodopa dose, and levodopa equivalent dose at baseline among both groups. UPDRS part III scores improved in both groups; however, there was also no significant difference between them. Conclusion: ISD could have efficacy to depression in some PD patients.

Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes

Parkinson's disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism. We examined memory performance and circadian rhythms in flies with loss-of-function mutations in two PD genes: PINK1 and parkin. We found learning and memory abnormalities in both mutant genotypes, as well as a weakening of circadian rhythms that is underpinned by electrophysiological changes in clock neurons. Our study paves the way for further work that may help us understand the mechanisms underlying these neglected aspects of PD, thus identifying new targets for treatments to address these non-motor problems specifically and perhaps even to halt disease progression in its prodromal phase.