Comparative Motor Pre-clinical Assessment in Parkinson's Disease Using Supervised Machine Learning Approaches.

ABSTRACTAim: This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. Materials and methods: The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. Results: Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: −1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: −2.6 ± 8.0; p < 0.0001). Conclusions: In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.

Impacts of dance on non-motor symptoms, participation, and quality of life in Parkinson disease and healthy older adults

Parkinson’s disease (PD) is characterized by motor and non-motor symptoms. Nutritional alterations are one of the non-motor symptoms that most influence the quality of life (QoL) in PD.ObjectiveTherefore, this review aims to evaluate whether nutritional alterations are related either to the severity of motor and non-motor symptoms through the gut-brain axis or to the different treatments for PD and whether all of this, in turn, impacts the QoL of patients.MethodsA systematic review was carried out in MEDLINE and EMBASE databases, and Mendeley from 2000 to June 2024, searching for articles related to nutritional alterations in PD that alter patients’ QoL. A total of 14 articles (2,187 participants) of 924 records were included.ResultsAmong the 14 studies examined, two investigated the relationship between nutritional status and QoL in patients with PD. Poor nutritional status was associated with lower QoL scores. Four studies explored the connection between nutritional status and its impact on both motor and non-motor symptoms (psychiatric disturbances, cognitive impairment, and fatigue), revealing a link between nutritional status, activities of daily living, and the severity of motor symptoms. Three studies identified changes in body weight associated with the severity of symptoms related to mobility issues in PD patients. Three studies investigated the relationship between different PD treatments and their interaction with changes in weight and energy metabolism, highlighting that weight loss in the early stages of PD needs adequate monitoring of different treatments, as well as the interaction between the central and peripheral nervous systems in regulating these processes. Finally, two studies investigated how gastrointestinal alterations and changes in the microbiota were related to cognitive status, thus identifying them as risk factors and early signs of PD.DiscussionThe systematic review highlighted the significant relationship between nutritional status and QoL in patients with PD, as well as how the PD treatments influenced their weight. An association was also observed in the gut-brain axis, where adequate nutritional status influenced the balance of intestinal microbiota, slowing cognitive decline, improving activities of daily living, and the QoL of PD patients. It is confirmed that the nutritional status of patients influenced both motor and non-motor symptoms of the disease, and therefore their QoL.

Nonmotor symptoms (NMS) in Parkinson's disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson's Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson's progressed. In conclusion, males experienced increased NMS burden in Parkinson's disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients' quality of life by therapeutically alleviating nonmotor symptoms.

Background: Non‐motor symptoms, quality of life, service needs, and barriers to care of individuals with movement disorders are not well explored. This study assessed these domains within a sample of individuals with essential tremor (ET) and Parkinson's disease (PD). Methods: A survey exploring symptoms, needs, and barriers to care was disseminated to a convenience sample (N = 96) of individuals with a primary diagnosis of ET (N = 19) or PD (N = 77). Results: Similarities in overall quality of life and impact on daily functioning were found across individuals with ET and PD. Noteworthy differences included endorsement of different types of service needs and utilization patterns and fewer non‐motor symptoms reported among those with ET (M = 6.1, SD = 2.4) than those with PD (M = 10.4, SD = 3.4). Non‐motor symptoms significantly impacted movement disorder‐related quality of life for both diagnostic groups, but this relationship was stronger for individuals with ET, t(12) = 3.69, p = 0.003, β = 0.73 than with PD, t(56) = 4.00, p less than 0.001, β = 0.47. Individuals with ET also reported higher rates of stigma (31.6% vs. 7.8%) and greater impact of non‐motor symptoms on emotional well‐being, R2 = 0.37, F(1, 13) = 7.17, p = 0.020. Discussion: This is the first study to describe and compare the needs, barriers to care, and impact on quality of life of two distinct movement disorder groups. Our results support the recent efforts of the field to identify interventions to address the non‐motor symptoms of movement disorders and indicate need for greater appreciation of the specific differences in symptoms and quality of life experienced across movement disorder diagnoses.

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson's disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson's disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (rs: 0.727, P < 0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson's disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study.

This paper presents advancements in machine learning and cloud deployment that enable rapid and accurate automated lithology interpretation. A supervised machine learning technique is described that enables rapid, consistent, and accurate lithology prediction alongside quantitative uncertainty from large wireline or logging-while-drilling (LWD) datasets. To leverage supervised machine learning, a team of geoscientists and petrophysicists made detailed lithology interpretations of wells to generate a comprehensive training dataset. Lithology interpretations were based on applying determinist cross-plotting by utilizing and combining various raw logs. This training dataset was used to develop a model and test a machine learning pipeline. The pipeline was applied to a dataset previously unseen by the algorithm, to predict lithology. A quality checking process was performed by a petrophysicist to validate new predictions delivered by the pipeline against human interpretations. Confidence in the interpretations was assessed in two ways. The prior probability was calculated, a measure of confidence in the input data being recognized by the model. Posterior probability was calculated, which quantifies the likelihood that a specified depth interval comprises a given lithology. The supervised machine learning algorithm ensured that the wells were interpreted consistently by removing interpreter biases and inconsistencies. The scalability of cloud computing enabled a large log dataset to be interpreted rapidly; &amp;gt;100 wells were interpreted consistently in five minutes, yielding &amp;gt;70% lithological match to the human petrophysical interpretation. Supervised machine learning methods have strong potential for classifying lithology from log data because: 1) they can automatically define complex, non-parametric, multi-variate relationships across several input logs; and 2) they allow classifications to be quantified confidently. Furthermore, this approach captured the knowledge and nuances of an interpreter's decisions by training the algorithm using human-interpreted labels. In the hydrocarbon industry, the quantity of generated data is predicted to increase by &amp;gt;300% between 2018 and 2023 (IDC, Worldwide Global DataSphere Forecast, 2019–2023). Additionally, the industry holds vast legacy data. This supervised machine learning approach can unlock the potential of some of these datasets by providing consistent lithology interpretations rapidly, allowing resources to be used more effectively.

Non-motor symptoms in Indian patients with Parkinson’s disease

Objective To investigate the clinical features of Parkinson disease(PD)with constipation. Methods From October 2013 to August 2015, a total of 204 PD patients were consecutively recruited from the Departments of Geriatrics and Neurology, Beijing Tiantan Hospital, Capital Medical University, and were evaluated by Rome Ⅲ diagnostic criteria for functional constipation and other related scales of motor symptoms(MS)and non-motor symptoms(NMS), the activity of daily living(ADL)and quality of life. Results Overall, 131 of 204(64.2%)PD patients with constipation were assigned to the PD-C group and 73 of 204(35.8%)PD patients without constipation were assigned to the PD-NC group.In the PD-C group, 38 of 131(29%)PD patients had constipation before motor symptoms occurred.The mean age and age of onset in the PD-C group were significantly older than those in the PD-NC group(64.13±9.67 vs.58.35±11.37; 60.07±10.46 vs.55.10±12.97; F=2.287, 4.948; t=-3.827, -2.788; P<0.01 for both). Meanwhile, compared with the PD-NC group, the PD-C group was associated with dramatically longer disease duration(2.25, range: 1.00-5.00 vs.2.00, range: 1.00-3.13; Z=-2.254; P<0.05), increased scores of the Unified Parkinson Disease Rating Scale(UPDRS)Ⅲ(26.00 scores, range: 18.00-37.50 vs.19.00, range: 12.50-31.00; Z=-2.349, P<0.05), more advanced stages on the Hoehn-Yahr(H-Y)scale(2.00 stage, range: 1.50-2.50 vs.1.50, range: 1.00-2.50; Z=-2.334, P<0.05), higher total numbers of NMS(11.00, range: 6.00-15.00 vs.6.00, range: 3.00-11.00; Z=-3.715, P<0.05), and higher numbers of NMS occurring before and after MS(before, 2.00, range: 0.00-4.00 vs.1.00, range: 0.00-2.00; after, 8.00, range: 3.00-14.00 vs.5.00, range: 2.00-9.50; Z=-2.612, -2.630, respectively; P<0.05 for both). Additionally, there were significant differences between the groups in the scores of the Hamilton depression scale(HAMD), the Hamilton anxiety scale(HAMA), the Pittsburgh sleep quality index(PSQI), the scales for outcomes in Parkinson disease-autonomic(SCOPA-AUT), the Fatigue severity scale(FSS), the Apathy scale, the Montreal Cognitive Assessment(MoCA)scale, the UPDRSⅡ and ADL Scale, and the PDQL-39(all P<0.05). Binary Logistic regression analysis showed that age, SCOPA-AUT, HAMA and HAMD were risk factors for PD-C(OR=1.091, 1.107, 1.10 and 1.080; P<0.05 for all). Conclusions PD patients have a high incidence of constipation, and more than a quarter of patients have constipation before MS occurs.Meanwhile, PD patients with constipation are usually associated with old age and late age of onset, long disease duration, severe MS, frequent and severe NMS, bad cognition, emotional state and sleep, severe fatigue, and apathy.Moreover, advanced age, autonomic dysfunction, anxiety and depression increase the risk of PD with constipation.Constipation has a serious negative impact on the activity of daily living and quality of life in PD patients. Key words: Parkinson disease; Constipation

Early-onset Parkinson's disease (EOPD) refers to patients with Parkinson's disease (PD) whose age at disease onset is less than 50 years. Literature on the non-motor symptoms (NMS) in these patients is very limited in the Indian context. We aimed to study the NMS in patients with EOPD and its impact on the quality of life (QoL). We included 124 patients with EOPD with a mean age at disease onset between 21 and 45 years and 60 healthy controls (HC). NMS were assessed using validated scales, and the QoL domains were evaluated using the PD QoL-39 scale (PDQ-39). The mean age at disease onset in EOPD patients was 37.33 ± 6.36 years. Majority of the patients were male (66.12%). The average disease duration was 6.62 ± 5.3 years. EOPD patients exhibited a significantly higher number of NMS per patient (7.97 ± 4.69) compared to HC (1.3 ± 1.39; p < 0.001). The most common NMS reported were urinary dysfunction, body pain, poor sleep quality, constipation, anxiety, depression, cognitive impairment, and REM sleep behavior disorder. The total NMS burden correlated with the QoL measures. Distinctive patterns of QoL subdomain involvement were identified, with sleep/fatigue, mood/cognition, and urinary dysfunction independently influencing QoL metrics. Our study provides valuable insights into the NMS profile and its impact on QoL in patients with EOPD, addressing an important knowledge gap in the Indian context. By understanding the specific NMS and their influence on QoL, healthcare professionals can develop targeted interventions to address these symptoms and improve the overall QoL.

BackgroundDisproportionately fewer females with Parkinson’s disease (PD) undergo deep brain stimulation surgery (DBS). Some data show worse depression, anxiety, and quality of life (QOL) in females with PD. Investigations into these gender disparities, or the effect of DBS on these non-motor symptoms, remain limited.Methods61 PD patients across seven UK DBS centres were recruited for the Clinical Response of Impulsive behaviours to deep brain Stimulation in PD (CRISP) prospective cohort study. Questionnaires measured primary outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and QOL (Parkinson’s Disease Questionnaire-39) before and 6 months after bilateral subthalamic nucleus DBS, and secondary outcomes of predictors of postoperative changes in mood.ResultsFemales were disproportionately under-referred for DBS (28% of cohort). Baseline depression and anxiety were similar between genders. While DBS significantly improved overall anxiety (p<0.001), females reported significantly more postoperative anxiety than males (median score 7 vs 1.5, Cohen’s d=0.33, p=0.009). Postoperatively, only males experienced a significant reduction in moderate depression, by 29% (p=0.004) (12% in females). QOL improved significantly by similar proportions, thus significantly worse QOL in females preoperatively was sustained as 9.12% worse postoperatively (Cohen’s d=0.75, p=0.02). Preoperatively, females reported significantly worse mobility, social support, and pain; postoperatively, the significant difference in mobility was sustained. Longer PD duration, worse QOL, and mobility predicted postoperative depression (R2=0.156, p=0.003), while female gender and reduced social support predicted postoperative anxiety (R2=0.23, p<0.001).ConclusionsDBS showed clinical efficacy for non-motor PD symptoms across genders, evidencing the need to close the gender gap in DBS. Analysis by gender highlighted significant disparities and postoperative predictors that provide impetus for tailored DBS counselling.

Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression.Methods/designObservational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson’s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson’s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson’s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private.DiscussionCOPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Non-motor symptoms are detrimental to health-related quality of life (HRQoL) of Parkinson's disease patients. In this study, the Non-Motor Symptoms Scale (NMSS) was used to assess the impact of the non-motor symptoms on HRQoL of Parkinson's disease patients. In a multicenter, international, cross sectional study on 411 Parkinson's disease patients, the NMSS was applied along with clinical (Hoehn and Yahr staging and SCOPA-Motor) and HRQoL measures (PDQ-39, and EQ-5D). Prevalence of non-motor symptoms was determined also through the NMSS. The association of NMSS and SCOPA-Motor with HRQoL measures and the differences in HRQoL scores between patients with and without non-motor symptoms in each NMSS domain were estimated by non-parametric statistics. Predictors of HRQoL were sought through multiple linear regression analyses. Nocturia (68.4% of the sample), fatigue (65.9%), and dribbling saliva (56.7%), were the most frequent complaints. Total NMSS score: (1) showed a higher correlation coefficient (r(S) = 0.70) with the PDQ-39 Summary Index (SI) than SCOPA-Motor (r(S) = 0.58); (2) showed high-moderate correlation (r(S) = 0.60 - 0.38) with all PDQ-39 domains; and (3) was the best predictor of HRQoL as measured by the PDQ-39 SI. For each NMSS domain, patients with symptoms had significantly worse HRQoL scores than patients without symptoms. To our knowledge, this is the first study to determine in a holistic manner the impact of the non-motor symptoms on HRQoL of Parkinson's disease patients. The results show that non-motor symptoms have, as a whole, a greater impact on HRQoL than motor symptoms and non-motor symptoms progression contributes importantly to HRQoL decline in patients with Parkinson's disease.

Numerous studies document significant improvement in motor symptoms in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). However, little is known about the initial effects of STN-DBS on nonmotor domains.Our objective was to elucidate the initial effects of STN-DBS on non-motor and motor symptoms in PD patients in a 4-month follow-up.This open prospective study followed 24 patients with PD who underwent STN-DBS. The patients were examined using dedicated rating scales preoperatively and at 1 and 4 months following STN-DBS to determine initial changes in motor and nonmotor symptoms. Patients at month 1 after STN-DBS had significantly reduced the Parkinson's disease Questionnaire scores (P = .018) and Scales for Outcomes in Parkinson's disease – Autonomic scores (P = .002); these scores had increased at Month 4 after DBS-STN. Nonmotor Symptoms Scale for Parkinson's Disease had improved significantly at Month 1 (P < .001); at Month 4, it remained significantly lower than before stimulation (P = .036). There was no significant difference in The Parkinson's Disease Sleep Scaleat Month 1 and significant improvement at Month 4 (P = .026). There were no significant changes in The Female Sexual Function Index or International Index of Erectile Function. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III scores show significant improvements at Month 1 (P < .001) and at Month 4 (P < .001).STN-DBS in patients with advanced PD clearly improves not only motor symptoms, but also several domains of nonmotor functions, namely sleep, autonomic functions and quality of life quickly following the start of stimulation.