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Introduction: Parkinson's disease patients may experience altered body image perception. Advanced Parkinson's disease (aPD) with motor complications often requires surgical and device-aided treatments (DAT), such as levodopa-carbidopa intestinal gel (LCIG) and deep brain stimulation (DBS). Understanding body image perception is crucial when managing these devices. This study aims to explore body image perception in aPD patients, hypothesizing a link between DAT and body image perception. Methods: We performed a cross-sectional study including non-demented aPD patients with and without DAT and age- and sex-matched controls. Participants were assessed using the Appearance Schemas Inventory-Revised (ASI-R), including Motivational Salience (MS) and Self-Evaluative Salience (SES) scores. Additional data included age, education, BMI, comorbidities, pharmacotherapy, and psychopathologies. PD patients were also evaluated with UPDRS, Hoehn and Yahr scales and LEDD calculation. Results: 70 aPD and 36 controls were enrolled. No differences in ASI-R scores were found between PD patients and controls, but women with PD had significantly lower MS scores than controls (16.1 ± 5.6 vs 19.7 ± 5.8; p = 0.023). Among aPD patients, those on DAT had longer disease duration, higher Hoehn and Yahr, and lower UPDRS IV scores. The lowest MS was observed in women on LCIG (12.7 ± 3.3; p = 0.001). Discussion: This study shows low MS ratings driven by female gender and LCIG treatment. Women on LCIG show reduced attention and management of their appearance. This may be influenced by cultural, environmental, and biological factors. Prospective research is needed to understand the impact of DAT on body image. [ABSTRACT FROM AUTHOR]

Background: Comorbidity of white matter lesions (WMLs) in idiopathic Parkinson's disease (PD) is becoming increasingly common. Objective: To analyze the risk factors and phenotypic differences for the occurrence and severity of WMLs in patients with PD. Methods: A total of 123 PD patients underwent clinical, laboratory, and magnetic resonance imaging (MRI) evaluations. Results: PD patients with WMLs were found to have a higher association with age, Modified Hoehn & Yahr stage (H-Y stage), and hypertension. There was a certain correlation between the severity of WMLs and PD phenotypes. 89% of PD patients had periventricular hyperintensities (PVH). Additionally, the score of the modified version of the Scheltens visual rating scale of PVH in the postural instability gait difficulty (PIGD) phenotype of PD was significantly higher than that in the tremor-dominant (TD) phenotype. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in the PIGD group were significantly lower than those in the TD group. Furthermore, compared with the TD group, the serum homocysteine level was significantly higher in the PIGD group. Conclusions: Age, H-Y stage, and hypertension are independent risk factors for WMLs in PD, and the severity of WMLs is related to the phenotype of PD patients. Our study found that PVH is the most common occurrence of WMLs in Parkinson's disease, and the burden of PVH is significantly higher in the PIGD phenotype compared to the TD phenotype of PD. Additionally, the PIGD phenotype is associated with more severe cognitive decline and elevated homocysteine levels. [ABSTRACT FROM AUTHOR]

Purpose: The development of modern Artificial Intelligence (AI) based models for the early diagnosis of Parkinson's disease (PD) has been gaining deep attention by researchers recently. In particular, the use of different types of datasets (voice, hand movements, gait, etc.) increases the variety of up-to-date models. Movement disorders and tremors are also among the most prominent symptoms of PD. The usage of drawings in the detection of PD can be a crucial decision-support approach that doctors can benefit from. Methods: A dataset was created by asking 40 PD and 40 Healthy Controls (HC) to draw spirals with and without templates using a special tablet. The patient-healthy distinction was achieved by classifying drawings of individuals using Support Vector Machine (SVM), Random Forest (RF), and Naive Bayes (NB) algorithms. Prior to classification, the data were normalized by applying the min-max normalization method. Moreover, Leave-One-Subject-Out (LOSO) Cross-Validation (CV) approach was utilized to eliminate possible overfitting scenarios. To further improve the performances of classifiers, Principal Component Analysis (PCA) dimension reduction technique were also applied to the raw data and the results were compared accordingly. Results: The highest accuracy among machine learning based classifiers was obtained as 90% with SVM classifier using non-template drawings with PCA application. Conclusion: The model can be used as a pre-evaluation system in the clinic as a non-invasive method that also minimizes environmental and educational level differences by using simple hand gestures such as hand drawing, writing numbers, words, and syllables. As a result of our study, preliminary preparation has been made so that hand drawing analysis can be used as an auxiliary system that can save time for health professionals. We plan to work on more comprehensive data in the future. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5–10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings. Methods: Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features. Results: A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion "age of onset < 55 years" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03). Conclusions: Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Medical treatment for tremors may include beta-blockers, primidone, dopaminergic, and anticholinergic drugs but it frequently leads to pharmacoresistance. Therefore, surgical treatment gained relevance as an alternative for those patients.We aim to evaluate radiosurgical thalamotomy as an effective and safe alternative to manage tremors. Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane Library databases were systematically searched for potential articles that evaluated radiosurgical thalamotomy for the management of tremor. Our analysis included 12 studies with 545 patients, 226 of whom were female. Of these, 64.6% of patients were diagnosed with essential tremor (ET), 34.6% with Parkinson's disease (PD), and 0.8% with both ET and PD. The FTM-TRS global score (MD -5.46; 95% CI [-10.44]-[-0.47]; I2 = 52%) and the drawing (MD -1.40; 95% CI [-2.03]-[-0.76]; I2 = 93%), drinking (MD -1.60; 95% CI [-1.82]-[-1.37]; I2 = 40%), and writing (MD -1.51; 95% CI [-1.89]-[-1.13]; I2 = 89%) grades showed significantly lower mean differences, favoring radiosurgical thalamotomy. A pooled proportion of 12% presented with tremor unchanged, while 38% presented with total elimination of tremor. Adverse events included: major paresis, minor paresis, dysarthria, and numbness. Thus, radiosurgical thalamotomy is a safe alternative for tremors resistant to medication, particularly in high-risk patients for RF or DBS procedures. The recommended dose of 130 to 150 Gy is effective and well-tolerated. However, randomized controlled trials (RCTs) are needed to understand the unpredictability of tissue response to radiation. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, but dopamine also plays a role in the pathophysiology of migraine. Objective: The aim of this study is to assess lifetime and previous year prevalence rates of headache in PD patients compared with controls. Patients and methods: We enrolled 101 patients (57 M and 44 W) and 101 controls (62 M and 39 W), comparable for age and gender, who underwent a semi-structured questionnaire to assess the occurrence and the features of headache, and Beck Depression Inventory (BDI). Results: We did not find any significant differences in the overall prevalence of lifetime and last 12-month headache between the two groups, as well as lifetime and last year tension-type headache (TTH) and migraine. Patients, especially those suffering from migraine and treated with dopamine agonists (DA), more frequently showed headache remission after the onset of motor symptoms compared to the age-related remission observed in controls (p = 0.001). Patients affected by headache were less frequently treated with DA in comparison with those without (p = 0.051). Depression of mood was more severe among PD patients with migraine than with TTH (p = 0.021). PD patients with headache exhibiting the akinetic-rigid subtype more frequently reported motor fluctuations than those presenting with tremor-dominant disease (p = 0.040). Conclusions: The prevalence of headache in PD follows that described in the general population, but dopaminergic pathway degeneration, loss of dopamine activation on the trigeminal-vascular system, and DA treatment might favor migraine improvement and remission in PD patients. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes into specific areas of the brain to treat a variety of medical conditions, including Parkinson's disease. Doubts and questions from patients prior to or following surgery should be addressed in line with the most recent scientific and clinical practice. ChatGPT emerges as an example of how artificial intelligence can be used, with its ability to comprehend and answer medical questions in an understandable way, accessible to everyone. However, the risks of these resources still need to be fully understood. ChatGPT models 3.5 and 4 responses to 40 questions in English and Portuguese were independently graded by two experienced specialists in functional neurosurgery and neurological movement disorders and resolved by a third reviewer. ChatGPT 3.5 and 4 demonstrated a good level of accuracy in responding to 80 questions in both English and Portuguese, related to DBS surgery for Parkinson's disease. The proportion of responses graded as correct was 57.5% and 83.8% for GPT 3.5 and GPT 4, respectively. GPT 3.5 provided potentially harmful answers for 6.3% (5/80) of its responses. No responses from GPT 4 were graded as harmful. In general, ChatGPT 3.5 and 4 demonstrated good performance in terms of quality and reliability across two different languages. Nonetheless, harmful responses should not be scorned, and it's crucial to consider this aspect when addressing patients using these resources. Considering the current safety concerns, it's not advisable for patients to use such models for DBS surgery guidance. Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is one of the most common symptoms of Parkinson's disease (PD), and may be detectable through changes in neural features visualized by magnetic resonance imaging (MRI). Mild cognitive impairment is a transitional state between normal aging and dementia, and early recognition of Parkinson's disease with mild cognitive impairment (PD-MCI) can help improve the quality of life and treatment for patients. This study investigated the association of enlarged perivascular space (EPVS) and white matter hyperintensity (WMH) with PD-MCI. Aims: This study aimed to evaluate whether EPVS and WMH can be used as potential MRI markers for PD-MCI. Methods: This retrospective study involved 200 patients with PD who underwent cranial MRI in our hospital from April 2021 to April 2022. Patients were divided into those with no cognitive impairment (PD-NCI) or mild cognitive impairment. Uni- and multivariate logistic regression analyzed associations of EPVS, WMH, and clinicodemographic characteristics with cognitive decline. Results: Univariate regression identified severe EPVS in basal ganglia, severe WMH, older age, late-onset, male sex, low educational level, longer duration of disease, low triglycerides, low uric acid, and low scores on the Mini-mental State Exam as risk factors for PD-MCI. After adjusting for clinicodemographic risk factors in multivariate regression, low education level and EPVS in basal ganglia remained risk factors for cognitive impairment. Conclusions: Severe EPVS in basal ganglia and poor education, but not WMH, are independent risk factors of PD-MCI. Our findings suggest that non-invasive detection of EPVS in basal ganglia by MRI may be a valuable early indicator of cognitive decline in PD patients. [ABSTRACT FROM AUTHOR]

Background: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. Methods: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. Results: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = − 0.456, p < 0.001) and UPDRS-III score (r = − 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. Conclusions: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) patients often experience non-motor symptoms like depression and anxiety, significantly impacting their quality of life. With the limited effectiveness of pharmacological treatments, effective non-pharmacological interventions are needed. This systematic review and meta-analysis aimed to evaluate the efficacy of cognitive-behavioral therapy (CBT) in reducing depression and anxiety symptoms in PD patients. Methods: Randomized controlled trials (RCTs) exploring CBT's effectiveness for depression and anxiety in PD patients were included. Studies published until April 2023 were identified from PubMed, Web of Science, and Scopus. Methodological quality was assessed using the Risk of Bias-2 (ROB-2) tool. Statistical analysis involved calculating the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) using Review Manager 5.4.1. Results: The systematic review included 12 studies involving 241 PD patients. CBT led to a substantial reduction in anxiety (SMD -0.95, 95% CI [-1.15 to -0.74], P < 0.00001) and depression (SMD -1.02, 95% CI [-1.39 to -0.65], P < 0.0001). Both traditional CBT and tele-CBT (administered over the phone or internet) were effective in treating depression and anxiety. Traditional CBT improved depression (SMD -1.16, 95% CI [-1.83 to -0.49], P < 0.00001), while tele-CBT showed comparable results (SMD -0.90, 95% CI [-1.31 to -0.48], P < 0.00001). For anxiety, both traditional CBT (SMD -0.94, 95% CI [-1.25 to -0.63], P < 0.00001) and tele-CBT (SMD -0.95, 95% CI [-1.22 to -0.67], P < 0.00001) significantly reduced symptoms. In conclusion, this systematic review and meta-analysis demonstrated the efficacy of CBT in reducing depression and anxiety in PD patients. Healthcare providers are encouraged to integrate CBT into their treatment protocols. However, additional high-quality studies with longer-term follow-up assessments are needed to further enhance understanding in this area. Prospero Registration: CRD42023424758. [ABSTRACT FROM AUTHOR]

Background: Altered gut metabolites, especially short-chain fatty acids (SCFAs), in feces and plasma are observed in patients with Parkinson's disease (PD). Objective: We aimed to investigate the colonic expression of two SCFA receptors, free fatty acid receptor (FFAR)2 and FFAR3, and gut barrier integrity in patients with PD and correlations with clinical severity. Methods: In this retrospective study, colonic biopsy specimens were collected from 37 PD patients and 34 unaffected controls. Of this cohort, 31 participants (14 PD, 17 controls) underwent a series of colon biopsies. Colonic expression of FFAR2, FFAR3, and the tight junction marker ZO-1 were assayed by immunofluorescence staining. The You Only Look Once (version 8, YOLOv8) algorithm was used for automated detection and segmentation of immunostaining signal. PD motor function was assessed with the Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS), and constipation was assessed using Rome-IV criteria. Results: Compared with controls, PD patients had significantly lower colonic expression of ZO-1 (p < 0.01) and FFAR2 (p = 0.01). On serial biopsy, colonic expression of FFAR2 and FFAR3 was reduced in the pre-motor stage before PD diagnosis (both p < 0.01). MDS-UPDRS motor scores did not correlate with colonic marker levels. Constipation severity negatively correlated with colonic ZO-1 levels (r = -0.49, p = 0.02). Conclusions: Colonic expression of ZO-1 and FFAR2 is lower in PD patients compared with unaffected controls, and FFAR2 and FFAR3 levels decline in the pre-motor stage of PD. Our findings implicate a leaky gut phenomenon in PD and reinforce that gut metabolites may contribute to the process of PD. [ABSTRACT FROM AUTHOR]

Background: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). Objective: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. Methods: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. Results: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. Conclusion: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints. [ABSTRACT FROM AUTHOR]

Objective: To examine the correlation between serum insulin-like growth factor 1 (IGF-1) and osteoporosis (OP) in Parkinson's disease (PD). Methods: We retrospectively analyzed clinical data from 105 PD patients (PD group) and 78 individuals in the health examination group (HC group). We compared general clinical data and serum IGF-1 levels between the two groups. PD patients were further categorized into PD with OP (50 cases) and PD without OP (55 cases) based on dual-energy X-ray absorptiometry (DXA) results for bone density. We compared general clinical data and serum IGF-1 levels between these two subgroups. Pearson correlation coefficient analysis was conducted to assess the relationship between serum IGF-1 levels and bone density at the lumbar spine and left femoral neck. Multifactorial logistic regression analysis was performed to identify risk factors for PD with OP. Results: Serum IGF-1 levels were significantly lower in the PD group compared to the HC group (P < 0.05). Pearson correlation analysis revealed a positive association between serum IGF-1 levels and both lumbar spine and left femoral neck bone densities (r = 0.653, P < 0.001; r = 0.625, P < 0.001). Multivariate logistic regression analysis identified decreased serum IGF-1 levels, lower uric acid levels, and higher H-Y stage as risk factors for PD with OP (P < 0.05). Conclusion: Reduced levels of serum IGF-1, uric acid, and an increased H-Y stage are closely linked to osteoporosis in PD. Elevating serum levels of IGF-1 and uric acid may potentially offer therapeutic avenues for PD with osteoporosis. [ABSTRACT FROM AUTHOR]

To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in Parkinson's disease (PD) patients. A comprehensive search strategy was implemented through August 15, 2023, and updated on February 13, 2024, across six databases, identifying studies relevant to unilateral focused ultrasound pallidotomy and PD. Eligibility criteria included observational studies, clinical trials, and case series reporting on the impact of the intervention on motor complications in PD patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment utilized appropriate tools for different study designs. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. Five studies were included in our study, involving 112 PD patients undergoing FUS pallidotomy. UPDRS-II analysis revealed a significant improvement from baseline (mean difference (MD): -3.205, 95% CI: -4.501, -1.909, P < 0.001). UPDRS-III overall change was significant (MD: -10.177, 95% CI: [-12.748, -7.606], P < 0.001). UPDRS-IV showed a significant change from baseline (MD: -5.069, 95% CI: [-5.915, -4.224], P < 0.001). UDysRS demonstrated a significant overall improvement (MD: -18.895, 95% CI: [-26.973, -10.818], P < 0.001). The effect of FUS pallidotomy on motor complications in PD patients was effective, with a significant decrease in the UPDRS and UDysRS, reflecting improvement. The incidence of adverse events (headaches, pin-site pain, difficulty walking, and sonication-related head pain) of the FUS pallidotomy was not statistically significant, indicating its safety. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD. [ABSTRACT FROM AUTHOR]

Background: REM Sleep Behavior Disorder (RBD) is characterized by absence of physiological muscle atonia during REM sleep (REM sleep without atonia, RWA). Nigro-striatal dopaminergic impairment is a feature of Parkinson disease (PD) and can be identified in prodromal stages as well, such as idiopathic RBD (iRBD). Aims of this study are to explore the efficacy of an automatic RWA quantification in identifying RBD patients and the correlation between RWA and nigro-striatal dopaminergic function. Methods: Forty-five iRBD, 46 PD with RBD, 24 PD without RBD patients and 11 healthy controls were enrolled in the Genoa Center (group A) and 25 patients with iRBD (group B) were enrolled in the Danish Center. Group A underwent brain [123I]FP-CIT-SPECT and group B underwent brain [18F]PE2I-PET as measures of nigro-striatal dopaminergic function. Chin muscle activity was recorded in all subjects and analyzed by applying a published automatic algorithm. Correlations between RWA and nigro-striatal dopaminergic function were explored. Results: The automatic quantification of RWA significantly differentiated RBD from non-RBD subjects (AUC = 0.86), although with lower accuracy compared with conventional visual scoring (AUC = 0.99). No significant correlation was found between RWA and nigro-striatal dopaminergic function. Conclusion: The automatic quantification of RWA is a reliable tool to identify subjects with RBD and may be used as a first-line screening tool, but without correlations with nigro-striatal dopaminergic functioning. [ABSTRACT FROM AUTHOR]

Background: Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). Methods: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. Results: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. Conclusion: This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disorder with an unexplored link to the cerebellum. In the pathophysiology of balance disorders in PD, the role of the flocculonodular lobe (FL) is linked to the impairment of the dopaminergic system. Dopamine deficiency can also lead to changes in cerebellum functions, disrupting balance control. This study compares cerebellar and FL volumes between healthy controls (HC) and PD patients, analyzing their correlation with clinical outcomes. Methods: We used magnetic resonance images of 23 PD patients (14 male, 9 female) and 24 HC (9 male, 15 female). Intracranial (ICV), total cerebellar, FL, and cerebellar gray matter volumes were measured using VolBrain. Clinical outcomes in PD patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-III) to evaluate motor function, with scores correlated to volumetric data. Results: The cerebellar and gray matter volumes in HC were 115.53 ± 10.44 cm3 and 84.83 ± 7.76 cm3, respectively, compared to 126.83 ± 13.47 cm3 and 92.37 ± 9.45 cm3 in PD patients, indicating significantly larger volumes in PD patients (p < 0.05). The flocculonodular lobe gray matter volume was 1.14 ± 0.19 cm3 in PD patients and 1.02 ± 0.13 cm3 in HC, but there was a significant increase in gray matter volume in PD patients between the groups (p < 0.05). In PD patients, significant negative correlations were observed between FL volume and the UPDRS-III scores (r = − 0.467, p = 0.033) and between UPDRS-III scores and both total (r = − 0.453, p = 0.039) and normalized (r = − 0.468, p = 0.032) gray matter volumes of the FL. Conclusion: Although total gray matter volumes were larger in PD patients, the volumes of FL did not differ between groups. In Parkinson's disease, increased cerebellar volume may regulate fine motor movements rather than balance. [ABSTRACT FROM AUTHOR]

Background: Essential tremor (ET) and Parkinson's disease (PD) are the two most prevalent movement disorders, sharing several overlapping tremor clinical features. Although growing evidence pointed out that changes in similar brain network nodes are associated with these two diseases, the brain network topological properties are still not very clear. Objective: The combination of graph theory analysis with machine learning (ML) algorithms provides a promising way to reveal the topological pathogenesis in ET and tremor-dominant PD (tPD). Methods: Topological metrics were extracted from Resting-state functional images of 86 ET patients, 86 tPD patients, and 86 age- and sex-matched healthy controls (HCs). Three steps were conducted to feature dimensionality reduction and four frequently used classifiers were adopted to discriminate ET, tPD, and HCs. Results: A support vector machine classifier achieved the best classification performance of four classifiers for discriminating ET, tPD, and HCs with 89.0% mean accuracy (mACC) and was used for binary classification. Particularly, the binary classification performances among ET vs. tPD, ET vs. HCs, and tPD vs. HCs were with 94.2% mACC, 86.0% mACC, and 86.3% mACC, respectively. The most power discriminative features were mainly located in the default, frontal-parietal, cingulo-opercular, sensorimotor, and cerebellum networks. Correlation analysis results showed that 2 topological features negatively and 1 positively correlated with clinical characteristics. Conclusions: These results demonstrated that combining topological metrics with ML algorithms could not only achieve high classification accuracy for discrimination ET, tPD, and HCs but also help to reveal the potential brain topological network pathogenesis in ET and tPD. [ABSTRACT FROM AUTHOR]

Background: Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. Methods: A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale—HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. Results: A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. Conclusion: Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is viewed as a progressively deteriorating neurodegenerative disorder, the exact etiology of which remains not fully deciphered to this date. The gut microbiota could play a crucial role in PD development by modulating the human immune system. Objective: This study aims to explore the relationship between gut microbiota and PD, focusing on how immune characteristics may both directly and indirectly influence their interaction. Methods: Utilizing cumulative data from genome-wide association studies (GWAS), our research conducted a two-sample Mendelian randomization (MR) analysis to clarify the association between the gut microbiome and PD. Additionally, by employing a two-step MR approach, we assessed the impact of gut microbiota on PD development via immune characteristics and quantified HLA-DR mediation effect on plasmacytoid dendritic cells (pDCs). Results: We discovered significant associations between PD and microbiota, comprising one class, one order, two families, and two genera. Furthermore, we explored the extent to which HLA-DR on pDCs mediates the effect of Butyrivibrio gut microbiota on PD. Conclusion: Our study emphasizes the complex interactions between the gut microbiota, immune characteristics, and PD. The relationships and intermediary roles identified in our research provide important insights for developing potential therapies that target the gut microbiome to alleviate symptoms in PD patients. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity). Methods: One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT). Results: Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05). Conclusions: In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function. [ABSTRACT FROM AUTHOR]

Introduction: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. Methods: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. Results: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. Discussion: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. Conclusion: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a prevalent neurodegenerative condition primarily affecting the elderly population. Despite its high incidence in aged individuals, there are no reliable blood-based biomarkers for clinical diagnosis of PD and early screening of susceptible individuals. Recent studies have revealed the significance of exosomes in mediating cell-to-cell communications by transferring bioactive molecules, such as proteins, nucleic acids (including miRNAs), lipids, and metabolites, between cells. Due to their ability to carry diverse molecular cargo and their involvement in various physiological and pathological processes, exosomes have gained significant attention as potential disease biomarkers. Notably, exosomes have the ability to cross the blood–brain barrier, and as a result, they can be found in circulating body fluids, including cerebrospinal fluid (CSF), serum, and plasma. Therefore, the identification of PD-specific exosomes in blood samples could be a promising avenue with biomarker potential for advancing clinical diagnosis and planning therapeutic strategies. This review highlights the current understanding of exosomal miRNAs in PD pathology, emphasising their potential for clinical utility as biomarkers even though several challenges may have to be overcome to precisely utilize exosomal miRNAs as biomarkers specific to PD. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). Methods: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. Results: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). Conclusion: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions. [ABSTRACT FROM AUTHOR]

Background: Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. Methods: N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB—which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. Results: The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. Discussion: In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research. [ABSTRACT FROM AUTHOR]

Purpose: Patients with Parkinson's disease (PD) exhibit various degrees of autonomic symptoms, which may be associated with Lewy body pathology distributed extensively in the autonomic nervous system. We hypothesized that the severity of autonomic symptoms reflects the severity of PD-related pathology, resulting in poor outcomes. The purpose of this study was to evaluate the impact of autonomic symptoms on PD progression. Methods: We conducted a follow-up study among consecutive patients with PD at Dokkyo Medical University Hospital. Patients underwent comprehensive baseline evaluations and were classified into high and low autonomic symptom groups using the Scale for Outcomes in Parkinson's Disease–Autonomic (SCOPA-AUT). The Kaplan‒Meier survival curves were used to analyze the time to discontinuation of their visits because of PD-related endpoints and to evaluate the association with high SCOPA-AUT scores. Results: Of the 101 patients, 74 (73%) met the inclusion criteria. During the follow-up period (mean 1654 days), 22/74 patients reached PD-related endpoints (death, 4; hospitalization, 9; nursing home institutionalization, 9). PD patients with high SCOPA-AUT scores reached the endpoints faster than those with low SCOPA-AUT scores. A high SCOPA-AUT score, including gastrointestinal, urinary, and thermoregulation domains; high motor symptom scores; and low specific binding ratios (SBRs) on 123I FP-CIT-SPECT (DAT-SPECT) were associated with reaching PD-related endpoints. A high SCOPA-AUT score was associated with reaching the endpoints even after adjustment for covariates. Conclusions: Patients with high autonomic symptom scores had a greater risk of reaching PD-related endpoints than patients with low autonomic symptom scores. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability. Methods: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson's disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman's correlation coefficients (rho) were used to determine construct validity, and Cronbach's alpha (α) was used to examine reliability. Results: The interquartile range of the NFOG-Q scores was 10.0–25.3 (range 0–29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515–0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319–0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96). Conclusions: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD. [ABSTRACT FROM AUTHOR]

Introduction: There is evidence to demonstrate that plasticity is "use-dependent" and that intensive practice may be necessary to modify neural organization. Purpose: The main aim of this work is to investigate the REACT usability, an innovative app, to assist People with Parkinson Disease (PwPD) at home. Methods: A pilot study has been conducted enrolling 20 consecutive PwPD. Before home rehabilitation activities started, each patient received training on the REACT app and how to use the device and the services in daily practice. Motor and cognitive evaluations were administered to assign personalized exercises, tailored to patients' needs and potential. PwPD carried out REACT home program for 1 month, four times a week. The app included motor exercise and tutorial of activities of daily living (ADL) and functional cognitive stimulation. REACT-app usability was evaluated with the System Usability Scale (SUS). Results: The results from SUS questionnaire were, on average, above the threshold of "good usability" (SUS score > 68), as reported in the literature. The 47% of PwPD that used the app rated the usability of the solution as "excellent." Almost all SUS items reached the reference benchmark (except items 4, 5, and 7). No adverse events occurred. Conclusions: REACT can be considered a useful and safe tool to support the continuity of care and treatment at home, in PwPD. Larger-scale trials are needed to validate the good acceptance and efficacy of home rehabilitation through technology applications. [ABSTRACT FROM AUTHOR]

Background: Comorbidity between myasthenia gravis (MG) and other autoimmune diseases is well-documented. However, concurrent MG and Parkinson's disease (PD) have rarely been described. This concurrence has mostly been considered coincidental in cases reported to date. Material/Methods: We characterized patients with concurrent MG and PD within a cohort of 631 MG patients by gender, age, MGFA class, quantitative MG score at diagnosis, UPDRS score at diagnosis, and the DaTSCAN uptake pattern, to determine the frequency and the phenotype of individuals with these two concurrent entities. Meta-analysis of cases in the literature was used for comparison with our series. Results: Eighteen cases were identified in which the two diseases were concurrent. The major characteristics of the phenotype are male prevalence, late-onset MG, and frequent initial symptoms of dropped head and oculobulbar involvement. DAT confirmed reduced bilateral uptake in eleven patients and reduced unilateral uptake in the others. Conclusions: To our knowledge, this is the largest reported series of concurrent MG and PD. This concurrence is more common than expected (2.85%). Either MG or PD may appear first. We found no iatrogenic relationship for the order of appearance. The overlapping of symptoms sometimes leads physicians to overlook the second disease, instead viewing it as a deterioration of the first. This study describes patients with well-documented diagnoses of both MG and PD, thus providing further indications of a shared etiology of these two diseases. Prospective studies including genetic, immunological, and environmental analysis are necessary to identify possible common pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a common neurodegenerative illness associated with motor symptoms. Aim: The aim of study was to compare the effects of synchronous telerehabilitation-based Lee Silverman Voice Treatment® BIG (LSVT® BIG) protocol and progressive structured mobility training in patients with Parkinson's disease (PD). Methods: Thirty-two patients diagnosed with PD (aged 40–72 years, Hoehn-Yahr stage 1–3) were randomly allocated into LSVT® BIG (Group 1) and Progressive Structured Mobility Training (Group 2) groups. Exercises were performed in both groups for 60 min a day, 4 days a week, for 4 weeks under the supervision of a physiotherapist with synchronous online videoconference method. Dynamic balance was assessed with Mini-Balance Evaluation Systems Test (Mini-BESTest) as a primary outcome measure. The secondary outcome measurements were Timed Up and Go Test (TUG), spatiotemporal parameters of gait from Kinovea® software, and postural stability from the Biodex Balance System. Other outcome measures were Activity-Specific Balance Confidence Scale-Short Form (ABC-SF), Parkinson's Activity Scale (PAS), and Parkinson's Disease Quality of Life Questionnaire (PDQ-39). Results: This study showed significant group-by-time interactions on Mini-BEST (p = 0.042), ABC-SF (p = 0.029), and PAS (p = 0.022) in favor of group 1. Also, TUG (p < 0.01), spatiotemporal parameters of gait (p < 0.01), and PDQ-39 (p < 0.01) were improved in both groups. Conclusion: Both synchronous telerehabilitation-based exercise protocols enhanced balance and gait, as well as activity level and quality of life in patients with PD. LSVT® BIG may be preferred to improve dynamic balance, balance confidence, and activity status in the early stages of PD. These results should be confirmed in future studies with more robust methodology. Trial registration: NCT04694872. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia 2 (SCA2) with a low range of CAG repeat expansion of ATXN2 gene can present with predominant or isolated parkinsonism that closely resembles Parkinson's disease (PD). This study is aimed at comparing clinical features, disease progression, and nuclear imaging between ATXN2-related parkinsonism (ATXN2-P) and PD. Methods: Three hundred and seventy-seven clinically diagnosed PD with family history were screened by multiplex ligation-dependent probe amplification, whole-exome sequencing or target sequencing, and dynamic mutation testing of 10 SCA subtypes. The baseline and longitudinal clinical features as well as the dual-tracer positron emission tomography (PET) imaging were compared between ATXN2-P and genetically undefined familial PD (GU-fPD). Results: Fifteen ATXN2-P patients from 7 families and 50 randomly selected GU-fPD patients were evaluated. Significantly less resting tremor and more symmetric signs were observed in ATXN2-P than GU-fPD. No significant difference was found in motor progression and duration from onset to occurrence of fluctuation, dyskinesia, and recurrent falls between the two groups. Cognitive impairment and rapid-eye-movement sleep behavior disorder were more common in ATXN2-P. During follow-up, olfaction was relatively spared, and no obvious progression of cognition dysfunction evaluated by Mini-Mental State Examination scores was found in ATXN2-P. PET results of ATXN2-P demonstrated a symmetric, diffuse, and homogenous dopamine transporter loss of bilateral striatum and a glucose metabolism pattern inconsistent with that in PD. Conclusions: Symmetric motor signs and unique nuclear imaging might be the clues to distinguish ATXN2-P from GU-fPD. [ABSTRACT FROM AUTHOR]

Introduction: Dubousset Functional Test (DFT) is an assessment test evaluating the functional capacity and dynamic balance. The study aimed to examine the reliability, validity, and responsiveness of the DFT in early stage Parkinson's disease (PD) patients. Methods: This was a cross-sectional study. Thirty-three early stage PD patients were recruited. The DFT was performed along with the Timed Up and Go (TUG) test, dual-task TUG, Functional Reach Test (FRT), 3-m backward walk test (3MBWT), Tinetti Performance-Oriented Mobility Assessment (POMA), and Berg Balance Scale (BBS). Results: The test–retest reliability of the subcomponents of the DFT was excellent. The ICCs were as follows: 0.952, 0.955, 0.917, and 0.919, respectively. The correlation with subcomponents of DFT and TUG, dual-task TUG, FRT, 3MBWT, BBS, and POMA was found to be statistically significant (p < 0.05). The standard measurement errors of the subcomponents of the DFT were 1.45, 1.39, 1.70, and 1.57, respectively. The minimal clinically important difference (MCID) of the subcomponents was 2.05, 1.97, 2.41, and 2.22, respectively. Conclusion: The DFT is a reliable, valid, and easy-to-administer tool in assessing the balance and physical function of early stage PD patients. [ABSTRACT FROM AUTHOR]

Introduction: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated. Methods: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication. Results: Subsyndromal ICDs manifestations were observed in 54% of the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and the clinical aspects of PD and dopaminergic medication. Conclusion: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD. [ABSTRACT FROM AUTHOR]

Background : Both motor and non-motor symptoms of Parkinson's disease (PD) have a substantial detrimental influence on the patient's quality of life. The most effective treatment remains oral levodopa. All currently known treatments just address the symptoms; they do not completely reverse the condition. Methodology: In order to find literature on the creation of novel treatment agents and their efficacy for PD patients, we searched PubMed, Google Scholar, and other online libraries. Results : According to the most recent study on Parkinson's disease (PD), a great deal of work has been done in both the clinical and laboratory domains, and some current scientists have even been successful in developing novel therapies for PD patients. Conclusion : The quality of life for PD patients has increased as a result of recent research, and numerous innovative medications are being developed for PD therapy. In the near future, we will see positive outcomes regarding PD treatment. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, and its incidence is rapidly rising. The diagnosis of PD relies on clinical characteristics. Although current treatments aim to alleviate symptoms, they do not effectively halt the disease's progression. Early detection and intervention hold immense importance. This study aimed to establish a new PD diagnostic model. Methods: Data from a public database were adopted for the construction and validation of a PD diagnostic model with random forest and artificial neural network models. The CIBERSORT platform was applied for the evaluation of immune cell infiltration in PD. Quantitative real-time PCR was performed to verify the accuracy and reliability of the bioinformatics analysis results. Results: Leveraging existing gene expression data from the Gene Expression Omnibus (GEO) database, we sifted through differentially expressed genes (DEGs) in PD and identified 30 crucial genes through a random forest classifier. Furthermore, we successfully designed a novel PD diagnostic model using an artificial neural network and verified its diagnostic efficacy using publicly available datasets. Our research also suggests that mast cells may play a significant role in the onset and progression of PD. Conclusion: This work developed a new PD diagnostic model with machine learning techniques and suggested the immune cells as a potential target for PD therapy. [ABSTRACT FROM AUTHOR]

Introduction: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. Methods: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. Results: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = − 0.277 ~ − 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50–100%, 47.22%–97.22%, and 0.673–0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922–1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. Conclusion: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants. Methods: In a selected cohort of 190 Hungarian patients with clinical signs of PD and suspected genetic risk, we performed the genetic testing of the GBA1 gene. As other genetic hits can modify clinical features, we also screened for additional rare variants in other neurodegenerative genes and assessed the APOE-ε genotype of the patients. Results: In our cohort, we identified 29 GBA1 rare variant (RV) carriers. Out of the six different detected RVs, the highly debated E365K and T408M variants are composed of the majority of them (22 out of 32). Three patients carried two GBA1 variants, and an additional three patients carried rare variants in other neurodegenerative genes (SMPD1, SPG11, and SNCA). We did not observe differences in age at onset or other clinical features of the patients carrying two GBA1 variants or patients carrying heterozygous APOE-ε4 allele. Conclusion: We need further studies to better understand the drivers of clinical differences in these patients, as this could have important therapeutic implications. [ABSTRACT FROM AUTHOR]

Backgound: Although cognitive control is essential for efficient gait, the associations between cognitive and motor networks regarding gait in individuals with Parkinson's disease (PD) remain to be determined. Herein, we enrolled 28 PD and 28 controls to compare internetwork coupling among cognitive and motor networks and examine its relationship with single- and dual-task gait performance in PD. Methods: The dorsal attention network (DAN), left and right frontoparietal control networks (FPNs), sensorimotor network, and lateral motor network were identified using resting-state functional magnetic resonance imaging data. The time taken to complete a 10-m walk test during cognitive or physical dual-tasks in PD was calculated representing gait performance. Results: We observed that the internetwork couplings between the DAN and motor networks and between the motor networks decreased whereas those between the left FPN and DAN and motor networks increased in PD compared to controls using a permutation test. There was no significant correlation between the internetwork couplings and single- and dual-task gait performance in PD. Nevertheless, improved cognitive dual-task performance showed a positive correlation with the DAN and left FPN coupling and a negative correlation with the DAN and lateral motor network coupling in a good performance group. The opposite relationship was observed in the poor cognitive dual-task performance group. Conclusion: Our findings suggest a neural mechanism of cognitive control on gait to compensate for reduced goal-directed attention in PD who maintain cognitive dual-task performance. [ABSTRACT FROM AUTHOR]

Introduction: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. Methods: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium–phosphate metabolism–related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). Results: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. Conclusion: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP). Methods: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed. Results: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others. Conclusions: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores. Methods: This study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2–4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores. Results: Twenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035–1.617; p = 0.024). Conclusion: This study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures. Trial registration number: jRCTs062220013. [ABSTRACT FROM AUTHOR]