Dysfunction In Parkinson's Disease Research Articles

Development and implementation of the frog-in-maze game to study upper limb movement in people with Parkinson’s disease

Upper-limb bradykinesia occurs early in Parkinson’s disease (PD) and bradykinesia is required for diagnosis. Our goal was to develop, implement and validate a game “walking” a frog through a maze using bimanual, alternating finger-tapping movements to provide a salient, objective, and remotely monitorable method of tracking disease progression and response to therapy in PD. Twenty-five people with PD and 16 people without PD participated. Responses on 5 different mazes were quantified and compared to spatiotemporal gait parameters and standard disease metrics in these participants. Intertap interval (ITI) on maze 2 & 3, which included turns, was strongly inversely related to stride-length and stride-velocity and directly related to motor UPDRS scores. Levodopa decreased ITI, except in maze 4. PD participants with freezing of gait had longer ITI on all mazes. The responses quantified on maze 2 & 3 were related to disease severity and gait stride-length, were levodopa responsive, and were worse in people with freezing of gait, suggesting that these mazes could be used to quantify motor dysfunction in PD. Programming our frog-in-maze game onto a remotely distributable platform could provide a tool to monitor disease progression and therapeutic response in people with PD, including during clinical trials.

A multiple hits hypothesis for memory dysfunction in Parkinson disease.

Cognitive disorders are increasingly recognized in Parkinson disease (PD), even in early disease stages, and memory is one of the most affected cognitive domains. Classically, hippocampal cholinergic system dysfunction was associated with memory disorders, whereas nigrostriatal dopaminergic system impairment was considered responsible for executive deficits. Evidence from PD studies now supports involvement of the amygdala, which modulates emotional attribution to experiences. Here, we propose a tripartite model including the hippocampus, striatum and amygdala as key structures for cognitive disorders in PD. First, the anatomo-functional relationships of these structures are explored and experimental evidence supporting their role in cognitive dysfunction in PD is summarized. We then discuss the potential role of α-synuclein, a pathological hallmark of PD, in the tripartite memory system as a key mechanism in the pathogenesis of memory disorders in the disease.

Multiculturalism and reported cognitive change in Parkinson's disease.

Subjective cognitive decline (SCD) and how much cognitive decline impacts one's ability to perform instrumental activities of daily living (iADLs) are necessary elements of neuropsychological assessment when diagnosing mild cognitive impairment (MCI) and dementia. Though limited, the literature suggests that culture and self-appraisal of cognitive abilities are related. However, it is unclear if differences exist in the subjective elements of neuropsychological assessments between patients born in Anglosphere countries (Canada, the USA, and the UK) versus immigrants born elsewhere (International Group). We conducted a retrospective chart review of advanced Parkinson's disease (PD) patients (n = 764). Reports of SCD and iADL difficulties were extracted from neuropsychological reports and coded by two independent raters. We also examined responses on self- and family-rated questionnaires of executive functioning and iADL difficulties. Anglosphere and International patients did not differ on overall, memory, or attention SCD, or overall iADL difficulties based on interviews. Anglosphere patients reported more executive and language SCD during the interview but International care-partners reported more current executive dysfunction on a questionnaire. International patients and care-partners reported more iADL difficulties on a questionnaire, which they ascribed to motor (not cognitive) symptoms. The effects on questionnaires were small and persisted after accounting for depression severity ratings. There were no consistent group differences in the number or pervasiveness of SCD or iADL difficulties reported by Anglosphere versus International groups. Immigration status has limited effect on these subjective elements and they should be given significant weight when diagnosing cognitive dysfunction in PD.

Urinary extracellular vesicle dynamics in Parkinson's disease patients with urinary dysfunction.

Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract. In this study, we have performed urinary EV analysis in 29 PD cases with varied severity of urinary dysfunction and correlated it with the EV dynamics in 29 age-matched controls. In the studied cases, apart from urinary dysfunction, symptoms of depression, anxiety, cognitive dysfunction, sleep, and wakefulness were observed in >75% of the cases. No significant difference in urinary EV size, concentration and urinary EV protein concentration was observed between PD cases with urinary dysfunction and controls. However, a significant positive association was observed between urinary EV concentration and motor scores (p = 0.042), while no association was observed between urinary EV concentration and urinary dysfunction scores. Chronic stress induced by motor symptoms could be one of the reasons for excessive EV production in PD patients with urinary dysfunctions. Large-scale studies on the association of urinary EV dynamics with motor and non-motor symptoms may provide additional information on urinary dysfunction in PD.

Harnessing artificial intelligence for enhanced Parkinson’s disease management: Pathways, treatment, and prospects

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the accumulation of misfolded proteins and impaired protein degradation mechanisms. Dysregulation of protein degradation processes, including autophagy and the ubiquitin-proteasome system, has been implicated in the pathogenesis of PD. Recently, artificial intelligence (AI) has emerged as a powerful tool to enhance our understanding of protein degradation in PD. This abstract provides an overview of the advancements in studying protein degradation in PD with the aid of AI. The integration of AI techniques, such as machine learning and data mining, has enabled the identification and characterization of protein degradation pathways involved in PD. By analyzing large-scale protein-protein interaction networks, AI algorithms have revealed key interactions and pathways underlying protein degradation dysfunction in PD. Furthermore, AI models can predict the efficiency of protein degradation processes and identify potential targets for enhancing protein degradation in PD, aiding in the development of novel therapeutic interventions.AI-based approaches have also been instrumental in drug discovery and target identification, as they can screen vast databases of compounds to identify potential drugs or small molecules that modulate protein degradation pathways relevant to PD. Additionally, deep learning algorithms have facilitated the analysis of protein structures, predicting protein stability and folding patterns that impact protein degradation. Moreover, AI has played a crucial role in the identification of protein biomarkers associated with protein degradation dysfunction in PD. These biomarkers can aid in early diagnosis and monitoring of the disease, enabling timely intervention and personalized treatment strategies. The advancements presented in this abstract highlight the transformative potential of AI in elucidating the intricate mechanisms of protein degradation in PD. Collaborations between AI researchers, biologists, and clinicians are essential to translate these findings into effective diagnostic tools and therapeutic interventions for PD patients.

4 Assessing Visuospatial Skills in Parkinson’s Disease Using the Identi-Fi

Objective:Patients with Parkinson’s disease (PD) commonly show deficits on tests of visuospatial functioning. The Identi-Fi is a new measure of visual organization and recognition composed of two components. The Visual Recognition (VR) subtest asks persons to identify an object that has been broken its pieces and rearranged, akin to the Hooper Visual Organization Test, but using updated and colorful pictures. The Visual Matching (VM) subtest involves showing the same stimuli, but the examinee must select the correct response from among five choices (1 correct and 4 foils), placing greater demand on visuospatial discrimination. Together, the two subtests comprise the Visual Organization Index (VOI), reflecting overall visual processing and organization ability. The present study examined performance on the Identi-Fi in patients with PD and its association with other aspects of cognition.Participants and Methods:Participants were 23 patients with PD (95% male; mean age = 69.7 years [SD = 7.8], range = 47-79) and 12 patients with cognitive concerns (CC) who were intact on neuropsychological testing (excluding consideration of Identi-Fi scores; 50% male, mean age = 71.08 [SD = 6.27], range = 60-78) seen for a neuropsychological evaluation at a large Northeastern medical center. As part of a larger battery, patients completed the Identi-Fi, Trail Making Test (TMT), Category Fluency, Test of Premorbid Functioning (TOPF), and Brief Visuospatial Memory Test, Revised (BVMT-R).Results:The PD group performed significantly worse than the CC group on VR and VM, as well as VOI, of the Identi-Fi (p < .001). Within the PD group, poorer VR, VM, and VOI performance was associated with lower scores on the TOPF (p < .05), BVMT-R learning (p < .05) and delayed recall (p < .05), as well as TMT Parts A and B (p < .05). VR was significantly correlated with Category Fluency (p < .05), while a trend was seen for the association between VOI and Category Fluency (p = .094).Conclusions:Identi-Fi performance was worse in the PD group than the CC group, which is consistent with prior research indicating that visuospatial processing is often abnormal in patients with PD. Furthermore, findings indicate that poorer performance on the Identi-Fi in the PD group is associated with poorer cognitive functioning in other domains (i.e., visuospatial learning and memory, processing speed, cognitive flexibility, and semantic fluency), as well as lower premorbid intellectual functioning. While these findings suggest that the Identi-Fi is useful in identifying visuospatial dysfunction in PD, findings should be interpreted with caution given the small sample sizes and uneven gender distribution

Comparison of tandospirone and escitalopram as a symptomatic treatment in Multiple System Atrophy-cerebellar ataxia: An open-label, non-controlled, 4 weeks observational study

BackgroundMultiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and motor dysfunction in parkinsonism and/or cerebellar ataxia. Patients with MSA usually present with depression and anxiety symptoms. This observational study of patients with MSA-cerebellar subtype (MSA-C) with subthreshold depression/anxiety symptoms aimed to compare the efficacy of escitalopram oxalate (an antidepressant drug) and tandospirone citrate (an anxiolytic drug). MethodsFifty-six MSA-C patients were included, with 28 patients in each treatment group. One group received escitalopram oxalate 10 mg/day and the other group received tandospirone citrate 30 mg/day. The patients were evaluated at baseline and after 4 weeks. Several psychiatric and neurological tests were performed, including the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Scale for the Assessment and Rating of Ataxia (SARA), and the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). Furthermore, post-void residual urine volume (PVR) and blood pressure were measured. ResultsThere was a more substantial reduction in the HAMA/HAMD, scores of stance, finger tracking, and finger nose test in the SARA, and PVR in the tandospirone group. There was a more substantial reduction in scores of dysuria, light-headed when standing up, syncope and hyperhidrosis in the SCOPA-AUT in the escitalopram group (p's < 0.05). ConclusionsTandospirone citrate was more effective in improving depression/anxiety and some cerebellar ataxia symptoms, whereas escitalopram was more effective in improving some autonomic symptoms in MSA-C patients over a short-term period in an open-label observational study without a control group. Further research is needed to evaluate the long-term effects of tandospirone and escitalopram in MSA-C in long-term placebo controlled trials.

Longitudinal Changes in Mitochondrial DNA Copy Number and Telomere Length in Patients with Parkinson's Disease.

Parkinson's disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case-control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation.

Metabolic Basis of Circadian Dysfunction in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The management of PD is a challenging aspect for general physicians and neurologists. It is characterized by the progressive loss of dopaminergic neurons. Impaired α-synuclein secretion and dopamine release may cause mitochondrial dysfunction and perturb energy metabolism, subsequently altering the activity and survival of dopaminergic neurons, thus perpetuating the neurodegenerative process in PD. While the etiology of PD remains multifactorial, emerging research indicates a crucial role of circadian dysfunction in its pathogenesis. Researchers have revealed that circadian dysfunction and sleep disorders are common among PD subjects and disruption of circadian rhythms can increase the risk of PD. Hence, understanding the findings of circadian biology from translational research in PD is important for reducing the risk of neurodegeneration and for improving the quality of life. In this review, we discuss the intricate relationship between circadian dysfunction in cellular metabolism and PD by summarizing the evidence from animal models and human studies. Understanding the metabolic basis of circadian dysfunction in PD may shed light on novel therapeutic approaches to restore circadian rhythm, preserve dopaminergic function, and ameliorate disease progression. Further investigation into the complex interplay between circadian rhythm and PD pathogenesis is essential for the development of targeted therapies and interventions to alleviate the burden of this debilitating neurodegenerative disorder.

Active ingredients of Chinese medicine with immunomodulatory properties: NF-κB pathway and Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease with a complex pathogenesis and no cure. Persistent neuroinflammation plays an important role in the development of PD, and activation of microglia and astrocytes within the central nervous system leads to an inflammatory response and production of pro-inflammatory factors, and activation of NF-κB is key to neuroglial activation in chronic inflammation in PD and a hallmark of the onset of neuroinflammatory disease. Therefore, inhibiting NF-κB activation to prevent further loss of dopaminergic nerves is a more effective means of treating PD. It has been found that an increasing number of active ingredients in Chinese medicines, such as flavonoids, alkaloids, saponins, terpenoids, phenols and phenylpropanoids, have anti-inflammatory properties that can regulate neuroglia cell activation and ameliorate neuroinflammation through the NF-κB pathway, and increase dopamine release or protect dopaminergic neurons for neuroprotection to improve behavioural dysfunction in PD. The active ingredients of traditional Chinese medicine are expected to be good candidates for the treatment of PD, as they provide holistic regulation through multi-targeting and multi-level effects, and are safe, inexpensive and readily available. Therefore, this paper summarises that the active ingredients of some relevant Chinese medicines ameliorate the symptoms of PD and delay the development of PD by inhibiting glial cell-mediated neuroinflammation through the NF-κB pathway, which may provide new ideas for exploring the molecular mechanism of PD pathogenesis and developing new anti-PD drugs.

Non-Pharmacological Treatment of Autonomic Dysfunction in Parkinson's Disease and Other Synucleinopathies.

Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted.

Hippocampal subfield vulnerability to α-synuclein pathology precedes neurodegeneration and cognitive dysfunction

Cognitive dysfunction is a salient feature of Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). The onset of dementia reflects the spread of Lewy pathology throughout forebrain structures. The mere presence of Lewy pathology, however, provides limited indication of cognitive status. Thus, it remains unclear whether Lewy pathology is the de facto substrate driving cognitive dysfunction in PD and DLB. Through application of α-synuclein fibrils in vivo, we sought to examine the influence of pathologic inclusions on cognition. Following stereotactic injection of α-synuclein fibrils within the mouse forebrain, we measured the burden of α-synuclein pathology at 1-, 3-, and 6-months post-injection within subregions of the hippocampus and cortex. Under this paradigm, the hippocampal CA2/3 subfield was especially susceptible to α-synuclein pathology. Strikingly, we observed a drastic reduction of pathology in the CA2/3 subfield across time-points, consistent with the consolidation of α-synuclein pathology into dense somatic inclusions followed by neurodegeneration. Silver-positive degenerating neurites were observed prior to neuronal loss, suggesting that this might be an early feature of fibril-induced neurotoxicity and a precursor to neurodegeneration. Critically, mice injected with α-synuclein fibrils developed progressive deficits in spatial learning and memory. These findings support that the formation of α-synuclein inclusions in the mouse forebrain precipitate neurodegenerative changes that recapitulate features of Lewy-related cognitive dysfunction.

Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson's disease.

Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson's disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

The Enigmatic CA2: Exploring the Understudied Region of the Hippocampus and Its Involvement in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease that affects both motor and non-motor functions. Although motor impairment is a prominent clinical sign of PD, additional neurological symptoms may also occur, particularly in the preclinical and prodromal stages. Among these symptoms, social cognitive impairment is common and detrimental. This article aims to review non-motor symptoms in PD patients, focusing on social cognitive deficits. It also examines the specific characteristics of the CA2 region and its involvement in social behavior, highlighting recent advances and perspectives. Additionally, this review provides critical insights into and analysis of research conducted in rodents and humans, which may help improve the understanding of the current status of putative therapeutic strategies for social cognitive dysfunction in PD and potential avenues related to the function of the hippocampal CA2 region.

Frequency, pattern and predictors of cognitive impairments in patients with Parkinson's disease using the Community Screening Instrument for Dementia.

Parkinson's disease (PD) is a chronic neurodegenerative disorder complicated by cognitive dysfunctions which are associated with increased caregiver burden, pressure on community health facilities, and mortality in affected patients. Most of the data concerning cognitive dysfunctions in PD are from studies conducted in Europe and North America, but there is paucity of data from Sub-Saharan Africa. The objective of this study is to determine the frequency, pattern and predictors of cognitive impairments amongst patients with Parkinson's disease. This was a cross sectional case control study carried out at a tertiary health facility in South-south Nigeria. Participants with PD were consecutively recruited from the neurology outpatient clinics. Demographic and disease-specific data were obtained with the use of a pre-tested questionnaire. Cognitive performance of thirty patients with PD were compared with thirty demographically matched controls using the Community Screening Instrument for Dementia (CSID). CSID was already validated among Nigerians. The frequency of cognitive impairment using the CSID was 50% for PD patients (3.3% for controls). Poor cognitive performance was observed across several cognitive domains including language, executive dysfunction, psychomotor speed, and constructional apraxia among PD patients. The independent predictors of the overall cognitive impairment in patients with PD determined by logistic regression analysis include recall deficiency (p = 0.007), impairment with naming (p = 0.044), apraxia (p = 0.003), Hoen&Yahr staging (p = 0.046), UPDRS score (p = 0.015) and age at presentation (p = 0.014). Cognitive impairments occur more frequently in patients with PD compared to controls. This study also demonstrated the predictive role of severity of disease based on Hoehn &Yahr staging and UPDRS score, and presence of recall deficiency, poor naming ability and apraxia.

Gastrointestinal Dysfunction in Parkinson's Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem.

Patients with Parkinson's disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.

The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson's disease.

Parkinson's disease (PD) is a complex progressive neurodegenerative disease associated with aging. Its main pathological feature is the degeneration and loss of dopaminergic neurons related to the misfolding and aggregation of α-synuclein. The pathogenesis of PD has not yet been fully elucidated, and its occurrence and development process are closely related to the microbiota-gut-brain axis. Dysregulation of intestinal microbiota may promote the damage of the intestinal epithelial barrier, intestinal inflammation, and the upward diffusion of phosphorylated α-synuclein from the enteric nervous system (ENS) to the brain in susceptible individuals and further lead to gastrointestinal dysfunction, neuroinflammation, and neurodegeneration of the central nervous system (CNS) through the disordered microbiota-gut-brain axis. The present review aimed to summarize recent advancements in studies focusing on the role of the microbiota-gut-brain axis in the pathogenesis of PD, especially the mechanism of intestinal microbiome dysregulation, intestinal inflammation, and gastrointestinal dysfunction in PD. Maintaining or restoring homeostasis in the gut microenvironment by targeting the gut microbiome may provide future direction for the development of new biomarkers for early diagnosis of PD and therapeutic strategies to slow disease progression.

Oligomeric Alpha-Synuclein and STX-1A from Neural-Derived Extracellular Vesicles (NDEVs) as Possible Biomarkers of REM Sleep Behavior Disorder in Parkinson's Disease: A Preliminary Cohort Study.

REM sleep behavior disorder (RBD) has a tighter link with synucleinopathies than other neurodegenerative disorders. Parkinson's Disease (PD) patients with RBD have a more severe motor and cognitive impairment; biomarkers for RBD are currently unavailable. Synaptic accumulation of α-Syn oligomers and their interaction with SNARE proteins is responsible for synaptic dysfunction in PD. We verified whether oligomeric α-Syn and SNARE components in neural-derived extracellular vesicles (NDEVs) in serum could be biomarkers for RBD. Forty-seven PD patients were enrolled, and the RBD Screening Questionnaire (RBDSQ) was compiled. A cut-off score > 6 to define probable RBD (p-RBD) and probable non-RBD (p non-RBD) was used. NDEVs were isolated from serum by immunocapture, and oligomeric α-Syn and SNARE complex components VAMP-2 and STX-1 were measured by ELISA. NDEVs' STX-1A resulted in being decreased in p-RBD compared to p non-RBD PD patients. A positive correlation between NDEVs' oligomeric α-Syn and RBDSQ total score was found (p = 0.032). Regression analysis confirmed a significant association between NDEVs' oligomeric α-Syn concentration and RBD symptoms (p = 0.033) independent from age, disease duration, and motor impairment severity. Our findings suggest that synuclein-mediated neurodegeneration in PD-RBD is more diffuse. NDEVs' oligomeric α-Syn and SNARE complex components' serum concentrations could be regarded as reliable biomarkers for the RBD-specific PD endophenotype.

Visual velocity perception dysfunction in Parkinson’s disease

ObjectiveCompared with motor deficits, sensory information processing in Parkinson’s disease (PD) is relatively unexplored. While there is increasing interest in understanding the sensory manifestations of PD, the extent of sensory abnormality in PD has remained relatively unexplored. Furthermore, most investigations on the sensory aspects of PD involve motor aspects, causing confounding results. As sensory deficits often arise in early PD development stages, they present a potential technological target for diagnosis and disease monitoring that is affordable and accessible. Considering this, the current study’s aim is to assess visual spatiotemporal perception independent of goal directed movements in PD by designing and using a scalable computational tool. MethodsA flexible 2-D virtual reality environment was created to evaluate various cases of visual perception. Using the tool, an experimental task quantifying the visual perception of velocity was tested on 37 individuals with PD and 17 age-matched control participants. Results: PD patients, both ON and OFF PD therapy, displayed perceptual impairments (p = 0.001 and p = 0.008, respectively) at slower tested velocity magnitudes. These impairments were even observed in early stages of PD (p = 0.015). ConclusionVisual velocity perception is impaired in PD patients, which suggests impairments in visual spatiotemporal processing occur in PD and provides a promising modality to be used with disease monitoring software. SignificanceVisual velocity perception shows high sensitivity to PD at all stages of the disease. Dysfunction in visual velocity perception may contribute to observed motor dysfunction in PD.