Fluoride Exposure as a Possible Environmental Modifier of Idiopathic Parkinson\u2019s Disease: Insights from a Rural North Indian Cohort

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons with motor symptoms of tremor, rigidity, bradykinesia and postural instability alongside non-motor symptoms such as constipation. Here we explore the effects of a novel antibiotic combination therapy (ACT) comprising Metronidazole, Vancomycin and Rifaximin for the treatment of constipation, which improved symptoms of PD in two cases. Our findings were validated by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to rank the burden of disease ranging from normal=0 to most severe=272. Case description/methods: Case 1 A 69 y/o male presented with PD and severe constipation including straining to initiate a bowel movement and inability to defecate for up to 1wk. Before commencing ACT, preliminary MDS-UPDRS was 38 and symptoms included asymmetric tremor, cogwheel rigidity, bradykinesia and shuffling gait despite treatment with Levodopa and Carbidopa. At 1yr review on ACT, constipation had abated with daily bowel motions not requiring Movicol. The MDS-UPDRS fell to 21 indicating a 45% reduction even with an unchanged PD medication regimen. Strikingly, there was a diminished tremor, milder cog-wheeling tone and minimal impairment of gait. After concluding ACT, the patient slowly regressed in line with the natural progression of disease. Case 2 A 62 y/o female presented with PD and a 10yr history of constipation, passing a bowel motion once every 4d with bloating and flatulence. Before ACT with added Colchicine was commenced, baseline MDS-UPDRS was 37 and symptoms included asymmetric tremor, rigidity, postural instability and decreased arm swing despite treatment with Pramipexole and Rasagiline. At 1yr follow-up on ACT, constipation had resolved with complete emptying daily and no bloating or flatulence. The MDS-UPDRS fell to 26 denoting a 30% reduction whilst the dosage of PD medication remained constant. Noticeably, there was a decreased frequency of tremor, absence of rigidity, improved balance and greater arm swing. Upon cessation of ACT, the patient had a sustained response and gained further success with self-initiated thiamine injections. Discussion: ACT successfully treated constipation and improved neurological symptoms of PD in two cases. Our findings suggest that treatments modulating the gut microbiota may play a role in reducing the severity and progression of PD as well as ameliorating non-motor symptoms such as constipation.Table 1.: Two cases with Parkinson’s Disease and Chronic Constipation who were treated with Antibiotic Combination Therapy PD: Parkinson’s Disease, MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (ranging from normal=0 to most severe=272), w: With, w/o: Without, BNO: Bowels not open, BO: Bowels open, i: One ii: Two, mg: Milligram, qd: Once a day, bd: Twice a day, qid: Four times a day.

Background Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, including gastrointestinal (GI) disturbances. Prodromal GI symptoms often precede motor symptoms, potentially serving as early indicators of the disease. This study aimed to assess the prodromal GI manifestations in idiopathic PD and explore their correlation with disease onset. Methods A retrospective cross-sectional study was conducted involving 41 idiopathic PD patients and 29 age- and sex-matched healthy controls. Clinical assessment was performed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). GI symptoms were evaluated using the Gastrointestinal Dysfunction Scale for Parkinson’s Disease (GIDS-PD), Gastrointestinal (GIT) Non-Motor Symptoms Scale (GIT-NMSS), and ROME IV criteria for irritable bowel syndrome (IBS). The relationships between GI symptoms and various disease characteristics were then examined through correlation analysis. Results PD patients exhibited significantly higher GI dysfunction compared to controls (p < 0.001), with constipation, drooling, and dysphagia being the most prevalent symptoms. The GIDS-PD total score was significantly correlated with disease duration, duration of GI manifestations, NMSS domain 6, and specific MDS- UPDRS items (constipation, drooling, and chewing/swallowing difficulties), with the most predicting variable being disease duration. Notably, GI symptoms often precede motor symptoms for several years. Conclusion Prodromal GI symptoms are common in idiopathic PD and correlate with disease progression. These findings suggest that early recognition of GI disturbances could facilitate earlier diagnosis and intervention, potentially improving disease management and patient outcomes.

ABSTRACTBackgroundBoth patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials.MethodWe studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2 years of follow‐up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4 years after baseline. To adjust for time‐varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g‐formula.ResultsWe included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS‐UPDRS Part III scores after 2 years of follow‐up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS‐UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale.ConclusionEarlier treatment initiation does not lead to worse MDS‐UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real‐world clinical decisions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

BackgroundEvaluating the discrepancies between patient‐reported measures and clinician examination has implications for formulating individual treatment regimens.ObjectiveThis study investigated the association between health outcomes and level of self‐reported motor‐related function impairment relative to clinician‐examined motor signs.MethodsRecently diagnosed PD patients were evaluated using the Parkinson's Progression Marker Initiative (PPMI, N = 420) and the PASADENA phase II clinical trial (N = 316). We calculated the average normalized difference between each participant's part II and III MDS‐UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) scores. Individuals with score differences <25th or >75th percentiles were labeled as low‐ and high‐self‐reporters, respectively (those between ranges were labeled intermediate‐self‐reporters). We compared a wide range of clinical/biomarker readouts among these three groups, using Kruskal–Wallis nonparametric and Pearson's χ2 tests. Spearman's correlations were tested for associations between MDS‐UPDRS subscales.ResultsIn both cohorts, high‐self‐reporters reported the largest impairment/symptom experience for most motor and nonmotor patient‐reported variables. By contrast, these high‐self‐reporters were similar to or less impaired on clinician‐examined and biomarker measures. Patient‐reported nonmotor symptoms on MDS‐UPDRS part IB showed the strongest positive correlation with self‐reported motor‐related impairment (PPMI rs = 0.54, PASADENA rs = 0.52). This correlation was numerically stronger than the part II and clinician‐examined MDS‐UPDRS part III correlation (PPMI rs = 0.38, PASADENA rs = 0.28).ConclusionSelf‐reported motor‐related impairments reflect not only motor signs/symptoms but also other self‐reported nonmotor measures. This may indicate (1) a direct impact of nonmotor symptoms on motor‐related functioning and/or (2) the existence of general response tendencies in how patients self‐rate symptoms. Our findings suggest further investigation into the suitability of MDS‐UPDRS II to assess motor‐related impairments. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Formulas were developed to define tremor dominant (TD) and postural instability/gait difficulty (PIGD) phenotypes of Parkinson's Disease (PD) using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). TD and PIGD designations, based on the original Unified Parkinson's Disease Rating Scale (UPDRS), provided useful designations for classifying different phenotypes of PD. With the advent of the MDS-UPDRS, a valid set of calculations for these phenotypes is needed. UPDRS and MDS-UPDRS scores were collected on 877 PD patients. TD/PIGD scores were calculated using the UPDRS formula for all patients. Comparable TD and PIGD items from the MDS-UPDRS were used to calculate new ratios. Data were analyzed using receiver operating characteristic models. The new MDS-UPDRS TD/PIGD ratios accounted for a significant area under the curve compared with the UPDRS classification. Optimal sensitivity and specificity were obtained with MDS-UPDRS cutoff scores of ≥1.15 for TD classification and ≤0.90 for PIGD. The development of comparable and valid PIGD and TD scores from the MDS-UPDRS provides a clear method for clinicians and researchers to transition from the original UPDRS to the new MDS-UPDRS in categorizing patients with different clinical phenotypes. © 2013 Movement Disorder Society.

Parkinson’s disease (PD) is one of the most prevalent neurological diseases, described by complex clinical phenotypes. The manifestations of PD include both motor and non-motor symptoms. We constituted an experimental protocol for the assessment of PD motor signs of lower extremities. Using a pair of sensor insoles, data were recorded from PD patients, Elderly and Adult groups. Assessment of PD patients has been performed by neurologists specialized in movement disorders using the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)-Part III: Motor Examination, on both ON and OFF medication states. Using as a reference point the quantified metrics of MDS-UPDRS-Part III, severity levels were explored by classifying normal, mild, moderate, and severe levels of PD. Elaborating the recorded gait data, 18 temporal and spatial characteristics have been extracted. Subsequently, feature selection techniques were applied to reveal the dominant features to be used for four classification tasks. Specifically, for identifying relations between the spatial and temporal gait features on: PD and non-PD groups; PD, Elderly and Adults groups; PD and ON/OFF medication states; MDS-UPDRS: Part III and PD severity levels. AdaBoost, Extra Trees, and Random Forest classifiers, were trained and tested. Results showed a recognition accuracy of 88%, 73% and 81% for, the PD and non-PD groups, PD-related medication states, and PD severity levels relevant to MDS-UPDRS: Part III ratings, respectively.

To assess the association between obstructive sleep apnea (OSA) and nonmotor symptoms (NMS), including cognitive dysfunction, in patients with Parkinson disease (PD). Patients with idiopathic PD, recruited from a movement disorder clinic, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. PD severity was assessed using the Hoehn & Yahr (H&Y) scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). NMS were assessed using the Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, Hospital Depression and Anxiety Scale, and PD sleep Scale. Sixty-seven patients (61.2% male), mean age 64.4 (SD 9.9) years and motor MDS-UPDRS 21.9 (12.6) using levodopa equivalent dose (LED) 752.4 (714.6) mg/d, were studied. OSA occurred in 47 patients (61.6%, mean AHI 27.1/h, SD 20.2/h), and NMS in 57 patients (85%). ESS and MoCA were associated with the AHI (ESS β = 0.0670, p = 0.031; MoCA β = -0.0520, p = 0.043, adjusted for age, sex, body mass index, LED, and H&Y). ESS was associated with respiratory arousals (β = 0.1015, p = 0.011) and intermittent hypoxemia (β = 0.1470, p = 0.006). MoCA was negatively associated with respiratory arousals (β = -0.0596, p = 0.049) but not intermittent hypoxemia. OSA is associated with sleepiness and cognitive dysfunction in PD, suggesting that OSA may be a reversible contributor to these NMS. Further studies will be required to evaluate whether OSA treatment can improve excessive sleepiness and cognitive dysfunction in PD.

Background: Metabolic syndrome and Parkinson's disease have common pathophysiological denominators. This study aimed to investigate how metabolic syndrome contributes to Parkinson's disease progression, as well as the genetic traits shared by PD and MetS. Methods: Four hundred and twenty-three newly diagnosed drug-naïve PD patients were analyzed from the Parkinson's Progression Markers Initiative (PPMI) database. We compared longitudinal changes in the total and subscale scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) between PD patients with and without metabolic syndrome over a five-year follow-up. We assessed the frequency of PD-associated genetic variants in both groups. Results: At baseline, Parkinson's patients with MetS were typically men (p < 0.01) and older (p = 0.04), with a higher Hoehn and Yahr score (p = 0.01) compared with their counterparts without MetS. They showed higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total scores at baseline and in follow-up years 2, 3, 4, and 5 (all p-values < 0.05) as analyzed by the Generalized Estimating Equation model. These differences were primarily driven by elevated motor scores (MDS-UPDRS Part III) (p < 0.01). MetS was associated with a higher frequency of the ZNF646.KAT8.BCKDK_rs14235 variant and a lower frequency of the NUCKS1_rs823118 and CTSB_rs1293298 variants. Conclusions: PD patients with MetS had worse motor symptomatology. Both conditions appear to share genetic susceptibility, involving genes related to lipid metabolism (BCKDK), autophagy and inflammation (CTSB), and chromatin regulation (NUCKS1).

BackgroundWorsening motor symptoms are associated with deteriorations in health‐related quality of life (HrQOL) in patients with Parkinson's disease (PD).AimBecause few studies have examined whether non‐motor symptoms (NMSs) predict worsening of overall NMSs and HrQOL, we investigated whether NMSs are associated with the changes in these outcomes in patients with PD.MethodsWe used data from J‐FIRST, a 52‐week study of patients with PD, ≥1 NMS, and wearing‐off under levodopa treatment. Changes in Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part I and 8‐item Parkinson's Disease Questionnaire (PDQ‐8) total scores during the observation period were compared between patients with and without individual NMSs at baseline. Relationships among NMSs were analyzed by cluster analysis.ResultsThe analyses comprised 996 patients. The MDS‐UPDRS Part I total scores significantly increased in patients with cognitive impairment, depressed mood, and apathy, but significantly decreased in patients with features of dopamine dysregulation syndrome, relative to the changes in patients without these NMSs at baseline. The PDQ‐8 total scores significantly increased in patients with cognitive impairment, hallucinations and psychosis, depressed mood, apathy, pain and other sensations, urinary problems, and fatigue relative to the changes in patients without these NMSs at baseline. NMSs were broadly clustered into cognitive/mental functions, and autonomic functions and sleep. Light headedness on standing, fatigue, and pain and other sensations were closely related.ConclusionWe observed significant deteriorations in the NMS burden and HrQOL in patients with cognitive, mental, or autonomic‐related NMSs.

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. 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. 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. 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.

BackgroundThe identification of biomarkers that reflect worse progression of nonmotor symptoms (NMS) in Parkinson's disease (PD) is currently an unmet need. The main aim of this study was to investigate whether cerebrospinal fluid (CSF) and serum neurofilament light (NfL), measured at baseline or longitudinally, can be used to predict the progression of NMS in patients with PD. MethodsBaseline and longitudinal NfL levels were measured in the CSF and serum in 392 PD patients and 184 healthy controls from the Parkinson's Progression Marker Initiative. NMS were assessed using several scales, including, but not restricted to, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). The relationship between baseline and longitudinal NfL levels with changes in NMS was assessed using linear mixed effects models (LME) in PD patients. In addition, we compared CSF and serum NfL levels between groups and assessed the relationship between NfL biomarkers with baseline NMS. Finally, to assess the specificity of our findings we ran the previous LME models using other biomarkers such as CSF amyloid-β1–42, total tau, phosphorylated tau181 and total α-synuclein and we also ran the models in healthy controls. ResultsBaseline levels and longitudinal changes in serum and CSF NfL predicted worse longitudinal MDS-UPDRS-I and depression scores over time in PD (p < 0.01). This relationship remained significant only for CSF NfL when controlling for motor and cognitive status. Furthermore, longitudinal changes in serum and CSF NfL were associated with worse anxiety over time in PD patients (p < 0.05). In contrast to CSF NfL, serum NfL levels were slightly higher at baseline (p = 0.043) and showed significant longitudinal increases (p < 0.001) in PD patients compared to controls. There were no significant correlations between NfL levels (CSF or serum) with other NMS scales, baseline NMS variables, other biomarkers or in healthy controls. ConclusionsOur findings indicate that both serum and CSF NfL are associated with worse longitudinal NMS burden, particularly in relation to the progression of depression and anxiety. Serum NfL showed stronger associations with NMS suggesting it could potentially be used as a non-invasive marker of NMS progression for PD.

BackgroundParkinson's disease (PD) is the most common neurodegenerative disorder after Alzheimer's disease, and is characterized by motor and non-motor symptoms, including gait dysfunction and cognitive decline. Dance has emerged as a promising intervention for improving motor and non-motor symptoms in persons with PD (PwPD), yet long-term effects remain underexplored.ObjectiveTo assess changes in cognitive function and gait performance over six years among PwPD who participated in a weekly dance program, compared to a Reference group who remained physically inactive.MethodsThis six-year longitudinal observational study included 43 PwPD who attended weekly dance classes and were evaluated using the Mini-Mental State Examination (MMSE) and Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS). A Reference group of 28 PwPD, matched on age, gender, and Hoehn & Yahr scores, were selected from the Parkinson's Progression Marker Initiative, and assessed using the MDS-UPDRS and Montreal Cognitive Assessment (MoCA). Cognitive scores were standardized. Generalized estimating equations were used to compare cognitive and gait outcomes across time.ResultsThe Dance group was significantly different from the Reference group (p < 0.001), with improved cognitive scores in 2016, 2017, and 2018. The Dance group had worse gait at baseline, however, the Reference group showed significantly poorer gait performance by 2018. In a subset of our data (n=10), no significant association was found between gait and cognitive scores.ConclusionsAfter two years of weekly dance, the Dance group showed improvements in cognition and maintained stability in gait performance. The findings highlight the potential neuroprotective benefits of continued dance engagement over six years.

This cross-sectional study aims to assess the levels of stigma among patients with Parkinson's disease (PD) and identify the demographic and clinical factors influencing both internal and external stigma. A total of 200 patients diagnosed with PD were recruited from Beijing Tiantan Hospital between June 2023 and June 2024 using convenience sampling. Data were collected through face-to-face interviews, including demographic information, disease severity assessed via the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and stigma levels measured using the 24-item Stigma Scale for Chronic Illness (SSCI). Statistical analyses included t-tests, ANOVA, correlation analysis, and multivariate linear regression. The average SSCI score among PD patients was 58.74 ± 13.73, with significant variation based on age, gender, educational level, marital status, disease duration, and motor subtype. Patients aged under 60, male, with lower educational attainment, divorced or widowed, and with longer disease duration had higher SSCI scores. MDS-UPDRS Part I-III scores were positively correlated with both internal and external stigma (r = 0.4, 0.5, and 0.5, respectively, p < 0.001). Multivariate linear regression analysis identified MDS-UPDRS scores, age, self-care ability, marital status, disease duration, and motor subtype as independent predictors of stigma. Stigma in PD is influenced by a combination of demographic and disease-related factors, particularly disease severity. Targeted interventions focusing on reducing motor and non-motor symptoms, as well as addressing social determinants, may help alleviate the stigma experienced by PD patients. These findings underscore the need for comprehensive management strategies that incorporate both clinical treatment and psychosocial support.

BACKGROUND: Brain ablation techniques are re-emerging as cost-effective alternatives to deep brain stimulation (DBS) in managing Parkinson’s disease (PD). These methods include thalamotomy, pallidotomy, subthalamotomy, and combined thalamotomy and pallidotomy aiming to improve motor symptoms and reduce medication requirements in patients with PD.OBJECTIVE: To assess the efficacy of four brain ablation techniques in improving motor symptoms, as measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, and reducing levodopa equivalent daily doses (LEDD) in patients with PD.METHODS: A prospective non-randomized study included 100 patients with PD who underwent thalamotomy, pallidotomy, subthalamotomy, or combined thalamotomy and pallidotomy. MDS-UPDRS Part III scores in "off" and "on" states and LEDD were evaluated preoperatively. Statistical analyses were conducted to compare changes across groups within 6 months follow up period. Postoperative complications were also documented.RESULTS: Six months postoperatively, significant reductions were observed in MDS-UPDRS scores and LEDD across the four studied groups. Subthalamotomy group demonstrated the most substantial improvements, with MDS-UPDRS "off" scores decreasing from 54.56 ± 6.07 to 28.32 ± 6.30 (P = 0.000012) and LEDD dropping from 770.00 ± 227.30 to 380.00 ± 116.82 (P = 0.00001). A statistically significant correlation between LEDD reduction and symptom improvement was noted in the pallidotomy (Rho = 0.424, p = 0.035) and subthalamotomy (Rho = 0.398, p = 0.049) groups.CONCLUSION: For patients with PD, brain ablation techniques can be significantly effective in improving the motor symptoms and in reducing the medication requirements.

BACKGROUND: Non-motor symptoms (NMSs) were a real burden in Parkinson’s disease (PD) and contributed to severe disability, impaired quality of life (QoL), and shortened life expectancy. AIM: The aim of this study was to investigate the prevalence of NMSs in PD and their correlation of NMS with disease duration, severity, and Unified Parkinson's Disease Rating Scale (UPDRS) motor score and their impact on patient’s QoL. MATERIALS AND METHODS: This was a prospective cross-sectional study. Sixty-four patients who were diagnosed by United Kingdom Parkinson's Disease Brain Bank criteria were studied. Non-motor symptom scale (NMSS) analyzed NMS, and motor dysfunction was assessed by the UPDRS II and III during OFF condition and QoL by Parkinson’s Disease Questionnaire-39 (PDQ-39) questionnaire. RESULTS: The prevalence of NMS was 93.75% (n = 60). Most frequent NMS was difficulty in falling asleep (54.7%), urinary urgency (39%), and memory impairment (37.5%). Most disabling symptoms are difficulty in falling asleep (3.34 ± 4.1) and fatigue (2.48 ± 4.2). The total NMSS scores were correlated with Hoehn and Yahr stage, and Movement Disorder Society UPDRS and PDQ-39 scores, but not with duration of disease. Correlation between NMSS and PDQ-39 scores was stronger as compared to the relationship between UPDRS and PDQ-39 scores (r = 0.71 and 0.58, respectively, P = 0.00). CONCLUSION: This study showed the high prevalence of NMSs and value of NMS as predictors of QoL in patients with PD. Therefore, understanding the pathophysiology of these NMSs should be placed at the forefront to develop new therapeutic approaches by improving the QoL of patients with PD.