Advanced Stages Of Parkinson's Disease Research Articles

The Prevalence of Depressive Symptoms in Patients with Idiopathic Parkinson's Disease: Cross-Sectional Study from Somalia.

Depression is one of the most common non-motor symptom of Parkinson's disease (PD), with an increasing prevalence in recent years. It causes significant psychological consequences that affect the disease course, overall quality of life, and functioning. The objective of this study was to determine the prevalence of depression in outpatients with Parkinson's disease evaluated in the neurology clinic at tertiary hospital in Mogadishu, Somalia. A cross-sectional study was conducted among 50 PD patients without dementia to determine the prevalence of depression at the neurology clinic of the Mogadishu Somalia Türkiye Training and Research Hospital between February and November 2022. All eligible participants were interviewed by a team of doctors using a structured questionnaire that consisted of sociodemographics and clinical characteristics, the Beck Depression Inventory-II (BDI-II) for depression assessment, and the Modified Hoehn and Yahr Scale for PD staging. Of the 50 PD participants, 60% were male and 58% were older than 60 years. 20% of them had a family history of PD and HTN as comorbid conditions. The prevalence of depression among the participants was 46% (95% CI 31.8-60.7). Of the patients with depression, 22% and 24% had mild and moderate depressive symptoms, respectively. The Mann-Whitney U-test revealed a statistically significant association between depression symptoms and the presence of comorbidity (χ2 = 136.50, p<0.01). The Kruskal-Wallis test revealed a statistically significant association between depression symptoms and a longer duration of PD (χ2 (2) = 18.21, p<0.01) and advanced stages of PD (χ2 (2) = 13.74, p<0.01). This is the first study conducted on patients with PD in Somalia and found that a significant proportion of these patients experienced depressive symptoms. We also highlighted that factors such the presence of medical comorbidities, high monthly income, advanced PD stage, longer duration of PD, and use of multiple medications for PD were significantly associated with the presence of depressive symptoms.

Evaluating a motor progression connectivity model across Parkinson's disease stages.

Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinicaltrial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is alsoassociated with improvements in long-term motor outcomes in patients with advanced-stage PD. Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance inlong-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). In early-stage PD, proximity of stimulation to the dorsolateral STN wasassociated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). Results suggest stimulation of a specific site in the dorsolateral STN isassociated with both slower motor progression and long-term motor improvements in PD.

Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review).

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of β-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.

Involvement of the basal forebrain and hippocampus in memory deficits in Parkinson's disease

IntroductionMagnetic resonance imaging (MRI)-determined atrophy of the nucleus basalis of Meynert (Ch4) predicts cognitive decline in Parkinson's disease (PD). However, interactions with other brain regions causing the decline remain unclear. This study aimed to describe how MRI-determined Ch4 atrophy leads to cognitive decline in patients with PD. MethodsWe evaluated 137 patients with PD and 39 healthy controls using neuropsychological examinations, MRI, and 123I-ioflupane single-photon emission computed tomography. First, we explored brain areas with regional gray matter loss correlated with Ch4 volume reduction using voxel-based morphometry (VBM). We then assessed the correlation between Ch4 volume reduction and cognitive impairments in PD using partial correlation coefficients (rpar). Finally, we examined whether the regional gray matter loss mediated the association between Ch4 volume reduction and cognitive impairments using mediation analysis. ResultsOur PD cohort was “advanced-stage enriched.” VBM analyses revealed that Ch4 volume loss was correlated with volume reduction in the medial temporal lobe in PD (P < 0.05, family-wise error corrected, >29 voxels). Ch4 volume reduction was significantly correlated with verbal memory deficits in PD when adjusted for age, sex, total brain volume, and 123I-ioflupane uptake in the caudate (rpar = 0.28, P < 0.001). The mediation analysis revealed that the hippocampus mediated the effects of Ch4 volumes on verbal memory (average causal mediation effect = 0.013, 95 % CI = 0.006–0.020, P < 0.001). ConclusionParticularly in advanced-stage PD, Ch4 atrophy was associated with medial temporal lobe atrophy, which played an intermediary role in the relationship between Ch4 atrophy and verbal memory impairments.

Vestibular Neurostimulation for Parkinson's Disease: A Novel Device-Aided Non-Invasive Therapeutic Option.

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson's disease (PD), but many unmet needs and gaps remain. Device-based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies. But there are concerns associated with these late-stage therapies due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and their limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low-risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps through the stimulation of the vestibular brainstem sensory network which extensively innervates brain regions, regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here, we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

Clinically established early Parkinson's disease patients do not show impaired use of priors in conditions of perceptual uncertainty

The ability to use past learned experiences to guide decisions is an important component of adaptive behavior, especially when decision-making is performed under time pressure or when perceptual information is unreliable. Previous studies using visual discrimination tasks have shown that this prior-informed decision-making ability is impaired in Parkinson's disease (PD), but the mechanisms underlying this deficit and the precise impact of dopaminergic denervation within cortico-basal circuits remain unclear. To shed light on this problem, we evaluated prior-informed decision-making under various conditions of perceptual uncertainty in a sample of 13 clinically established early PD patients, and compared behavioral performance with healthy control (HC) subjects matched in age, sex and education. PD patients and HC subjects performed a random dot motion task in which they had to decide the net direction (leftward vs. rightward) of a field of moving dots and communicate their choices through manual button presses. We manipulated prior knowledge by modulating the probability of occurrence of leftward vs. rightward motion stimuli between blocks of trials, and by explicitly giving these probabilities to subjects at the beginning of each block. We further manipulated stimulus discriminability by varying the proportion of dots moving coherently in the signal direction and speed-accuracy instructions. PD patients used choice probabilities to guide perceptual decisions in both speed and accuracy conditions, and their performance did not significantly differ from that of HC subjects. An additional analysis of the data with the diffusion decision model confirmed this conclusion. These results suggest that the impaired use of priors during visual discrimination observed at more advanced stages of PD is independent of dopaminergic denervation, though additional studies with larger sample sizes are needed to more firmly establish this conclusion.

In-Patient Multimodal Intensive Neurorehabilitation and Care Improve Motor and Non-Motor Functions in the Moderately Advanced Stages of Parkinson's Disease: A Retrospective Study in a U.S. Facility.

(1) Background: Previous studies, mostly performed in European centers, have shown that in-patient multimodal intensive rehabilitation treatments lasting for two to four weeks can improve both motor and non-motor symptoms of Parkinson's disease (PD) with long-lasting effects. Here, we ascertain the effects of a similar in-patient program in a U.S. center with a retrospective study in a cohort of 153 patients in the moderately advanced stage of PD. (2) Methods: We compared indices of motor and non-motor functions before and immediately after such treatment and investigated the possible differences between men and women. We used the available records of the Beck Depression Inventory, PDQ39, PD Sleep Scale, Timed Up and Go, Vocal Volume, Voice Handicap, and total UPDRS scores. (3) Results: We found that at the end of treatment, which lasted an average of 14 days, all outcome measures significantly improved independently of sex. (4) Conclusions: These results confirm the previous findings with a similar in-patient approach in European centers. They further suggest that this in-patient treatment is a care model that is feasible in U.S. centers and can provide a more immediate benefit to the motor function and quality of life of patients with moderately advanced PD.

Risk factors for 3-year mortality in selected patients with Parkinson's disease from a Romanian cohort.

This study aimed to identify and analyze factors associated with a higher risk of 3-year mortality in patients with Parkinson's disease (PD) within a Romanian cohort, focusing on individuals with more advanced disease stages as indicated by the Hoehn and Yahr scale. We conducted a cross-sectional observational study on 42 patients with PD treated at the Neurology Clinic I, Cluj-Napoca County Emergency Clinical Hospital, between October 2019 and January 2021. All participants were at stages 2.5 or 3 on the Hoehn and Yahr scale at baseline. Various clinical, neuropsychological, and neurophysiological assessments were performed, including evaluations for motor and non-motor symptoms such as anhedonia (via the Snaith-Hamilton Pleasure Scale - SHAPS) and cognitive impairment. The use of antiparkinsonian medications and antidepressants was also recorded. Factors associated with higher mortality risk included a higher anhedonia score (SHAPS > 34; P = 0.03), higher levodopa doses (cutoff = 937.5 mg; P = 0.001), and the administration of mirtazapine (P = 0.04). These findings indicate that non-motor symptoms like anhedonia, along with higher medication doses and specific treatments, play a significant role in influencing mortality risk in advanced PD. This study highlights the multifaceted nature of mortality risk in patients with PD, particularly emphasizing the role of non-motor symptoms and pharmacological treatment. Tailored therapeutic strategies, including closer monitoring of anhedonia and careful management of medication dosages, may be essential in reducing mortality and improving patient outcomes in advanced stages of PD.

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson's disease.

Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear. In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients. Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = -0.27, p = 0.003) and the putamen (β = -0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = -0.37, p = 0.013; putamen: β = -0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011). Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.

Therapeutic singing-induced swallowing exercise for dysphagia in advanced-stage Parkinson's disease.

With longer life spans and medical advancements, the rising number of patients with advanced-stage Parkinson's disease (PD) warrants attention. Current literature predominantly addresses dementia and fall management in these patients. However, exploring the impact of swallowing function on patients with advanced PD is crucial. Previous research has demonstrated notable enhancements in the quality of life related to voice for participants following a group singing-intervention program. To further elucidate the effect of individual singing-induced swallowing exercises, our study aimed to investigate the quantitative and qualitative effects of therapeutic singing on swallowing function in patients with advanced PD in comparison to a matched usual care control group. The hypothesis of this study is that therapeutic singing-induced swallowing exercises can assist to maintain swallowing function in patients with advanced PD. This prospective matched control study compared the effects of a 6-week therapeutic singing-based swallowing intervention on swallowing function and quality of life in patients with advanced PD. The intervention group received individual sessions with a music therapist and conventional individual physical therapy. The control group received the same standard physical therapy for 6 weeks without music intervention. The primary outcome measure was Video Fluoroscopic Dysphagia Scale (VDS). The study revealed that the intervention group maintained swallowing function, whereas the control group experienced deterioration, indicating significant time-dependent changes in Penetration-Aspiration Scale (PAS), National Institutes of Health-Swallowing Safety Scale (NIH-SSS), and VDS. Analysis of PAS and NIH-SSS liquid food scores in both groups showed significant time effects. However, the intervention group exhibited no significant differences between the pre- and post-tests, indicating preservation of the swallowing function. VDS of liquid food indicated an interaction effect between time and group in the pharyngeal phase and total scores. The Swallowing-Quality of Life showed significant time-effect improvement in the intervention group. Therapeutic singing exercises may help maintain swallowing function in advanced PD patients, potentially enhancing quality of life related to swallowing in those with advanced-stage diseases. https://cris.nih.go.kr/cris/search/listDetail.do, identifier KCT0008644.

Patient With Parkinson Disease and Care Partner Perceptions of Key Domains Affecting Health-Related Quality of Life: Systematic Review

To effectively customize Parkinson disease (PD) programs, it is important to incorporate the "individual's voice" and have a thorough understanding of the symptom priorities of people with PD (PwP) and care partners (CP). In this convergent integrated mixed-method systematic review, we aimed to analyze qualitative and quantitative evidence of PD motor and nonmotor symptoms affecting health-related quality of life (HRQOL) in PwP and CP, comparing priorities across different levels of disease severity. We searched MEDLINE, PsycINFO, Web of Science, Embase, and Scopus; ProQuest Dissertations and Theses Global; and the Michael J. Fox Foundation Data Resources for studies published up to June 29, 2022. We included qualitative, quantitative, and mixed-method studies investigating PD symptom priorities among PwP and CP. We critically appraised eligible studies for methodological quality using the Mixed-Methods Appraisal Tool. Derived terms were mapped and coded according to thematic attribution. Independent syntheses of qualitative and quantitative evidence and transformation of quantitative data into qualitative formats were performed. Of the 7,716 identified studies, we included 70 that provided qualitative (n = 13), quantitative (n = 53), and mixed (n = 4) evidence. We included 604 mapped terms representing 11 PwP-identified and CP-identified motor and nonmotor symptom categories. Across all PD stages, both PwP and CP considered 5 domains more affecting their HRQOL, namely: "motor functionality," "mood," "cognition," "gait, balance, posture, and falls," and "nighttime sleep disorders." In early disease, PwP and CP considered "mood" the domain that most affected their HRQOL. In advanced PD, PwP considered "pain" the domain that most affects their HRQOL, while CP considered "psychiatric symptoms." The domain "gait, balance, posture, and falls" was equally considered by both PwP and CP as the second domain that most affects their HRQOL in the advanced stage of PD. The ranking of the priority of symptoms is largely shared by PwP and CP, and motor symptom priorities dominate the full disease spectrum. However, the nonmotor symptom priorities shift according to the disease severity stage. Tailored care and research require that providers consider these shifting priorities and incorporate the "individual's voice" into treatment decisions.

Motor and process skills of people with parkinson's disease compared to healthy older adults. A cross-sectional study.

Both Parkinson's disease (PD) and the process of ageing are associated with functional limitations. The aim of this study was to determine the differences in motor and process skills between individuals with PD and healthy older adults, as well as to observe how disease progression affects motor and process skills performance in PD patients. A cross-sectional study was conducted. The Assessment of Motor and Process Skills (AMPS) measure was employed in order to analyze the differences in the motor and process skills of daily tasks in people with PD and healthy older adults age- and sex-matched. Part III of the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr (HY) scale and the Schwab & England scale was administered to determine the severity of the disease. Seventy participants (49 patients with PD and 21 healthy older adults) were recruited for this study. Our results showed that even at moderate stages of the disease, both motor and process skills were found deteriorated in PD patients more than older healthy older adults (p < 0.001). As PD progresses, motor and process skills present significantly deterioration. PD leads to a greater deterioration in motor and process skills compared to healthy older adults. As disease stages advance according to the HY scale, performance in motor and process skills deteriorates significantly between moderate and advanced PD stages. According to the AMPS scale, PD patients show no impairment of processing skills up to HY IV, but motor impairment at HY stages II, III and IV.

Spatiotemporal patterns of brain iron-oxygen metabolism in patients with Parkinson's disease.

Iron deposition and mitochondrial dysfunction are closely associated with the genesis and progression of Parkinson's disease (PD). This study aims to extract susceptibility and oxygen extraction fraction (OEF) values of deep grey matter (DGM) to explore spatiotemporal progression patterns of brain iron-oxygen metabolism in PD. Ninety-five PD patients and forty healthy controls (HCs) were included. Quantitative susceptibility mapping (QSM) and OEF maps were computed from MRI multi-echo gradient echo data. Analysis of covariance (ANCOVA) was used to compare mean susceptibility and OEF values in DGM between early-stage PD (ESP), advanced-stage PD (ASP) patients and HCs. Then Granger causality analysis on the pseudo-time-series of MRI data was applied to assess the causal effect of early altered nuclei on iron content and oxygen extraction in other DGM nuclei. The susceptibility values in substantia nigra (SN), red nucleus, and globus pallidus (GP) significantly increased in PD patients compared with HCs, while the iron content in GP did not elevate obviously until the late stage. The mean OEF values for the caudate nucleus, putamen, and dentate nucleus were higher in ESP patients than in ASP patients or/and HCs. We also found that iron accumulation progressively expands from the midbrain to the striatum. These alterations were correlated with clinical features and improved AUC for early PD diagnosis to 0.824. Abnormal cerebral iron deposition and tissue oxygen utilization in PD measured by QSM and OEF maps could reflect pathological alterations in neurodegenerative processes and provide valuable indicators for disease identification and management. Noninvasive assessment of cerebral iron-oxygen metabolism may serve as clinical evidence of pathological changes in PD and improve the validity of diagnosis and disease monitoring. • Quantitative susceptibility mapping and oxygen extraction fraction maps indicated the cerebral pathology of abnormal iron accumulation and oxygen metabolism in Parkinson's disease. • Iron deposition is mainly in the midbrain, while altered oxygen metabolism is concentrated in the striatum and cerebellum. • The susceptibility and oxygen extraction fraction values in subcortical nuclei were associated with clinical severity.

Hybrid Machine Learning Framework for Multistage Parkinson's Disease Classification Using Acoustic Features of Sustained Korean Vowels.

Recent research has achieved a great classification rate for separating healthy people from those with Parkinson's disease (PD) using speech and the voice. However, these studies have primarily treated early and advanced stages of PD as equal entities, neglecting the distinctive speech impairments and other symptoms that vary across the different stages of the disease. To address this limitation, and improve diagnostic precision, this study assesses the selected acoustic features of dysphonia, as they relate to PD and the Hoehn and Yahr stages, by combining various preprocessing techniques and multiple classification algorithms, to create a comprehensive and robust solution for classification tasks. The dysphonia features extracted from the three sustained Korean vowels /아/(a), /이/(i), and /우/(u) exhibit diversity and strong correlations. To address this issue, the analysis of variance F-Value feature selection classifier from scikit-learn was employed, to identify the topmost relevant features. Additionally, to overcome the class imbalance problem, the synthetic minority over-sampling technique was utilized. To ensure fair comparisons, and mitigate the influence of individual classifiers, four commonly used machine learning classifiers, namely random forest (RF), support vector machine (SVM), k-nearest neighbor (kNN), and multi-layer perceptron (MLP), were employed. This approach enables a comprehensive evaluation of the feature extraction methods, and minimizes the variance in the final classification models. The proposed hybrid machine learning pipeline using the acoustic features of sustained vowels efficiently detects the early and mid-advanced stages of PD with a detection accuracy of 95.48%, and with a detection accuracy of 86.62% for the 4-stage, and a detection accuracy of 89.48% for the 3-stage classification of PD. This study successfully demonstrates the significance of utilizing the diverse acoustic features of dysphonia in the classification of PD and its stages.

Irritable bowel syndrome based on Rome IV diagnostic criteria associates with non-motor symptoms of Parkinson's disease

BackgroundRecent concepts suggest that the neuropathological hallmark of Parkinson's disease (PD) may in part originate from the enteric nervous system. We evaluated the frequency of functional gastrointestinal disorders in PD patients using Rome IV criteria and correlated the clinical severity of PD. MethodsPD patients and matched controls were recruited between January 2020 and December 2021. Rome IV criteria were used to diagnose constipation and irritable bowel syndrome (IBS). Severity of PD motor symptoms was evaluated using UPDRS part III scores and non-motor symptoms using Non-motor Symptoms Scale (NMSS). ResultsA total of 99 PD patients and 64 controls were enrolled. The prevalence of constipation (65.7% vs. 34.3%, P < 0.001) and IBS (18.1% vs 5%, P = 0.02) were significantly higher in PD patients than controls. The prevalence of IBS was higher in early-stage PD than advanced-stage PD (14.43% vs. 8.25%, P = 0.02), whereas constipation was more common in advanced stages (71.43% vs. 18.56%, P < 0.001). PD patients with IBS had higher NMSS total scores (P < 0.01) than those without IBS. The severity of IBS correlated with NMSS scores (r = 0.71, P < 0.001), especially subscores in domain 3 assessing mood disorders (r = 0.83, P < 0.001), but not UPDRS part III scores (r = 0.06, P = 0.45). The severity of constipation correlated with the UPDRS part III scores (r = 0.59, P < 0.001) but not the domain 3 mood subscores (r = 0.15, P = 0.07). ConclusionThe prevalence of IBS and constipation was higher in PD patients than controls and phenotypic correlation supported the occurrence of IBS with higher non-motor symptom burden, especially mood symptoms, in PD patients.

Controlled-Release Levodopa for the Treatment of Rapid Motor Fluctuations in Parkinson's Disease Subjects with Subthalamic Nucleus Deep Brain Stimulation.

Objectives We aimed to investigate the efficiency of controlled-release levodopa/benserazide (Madopar HBS) use during daytime in our pilot study on advanced-stage Parkinson's disease (PD) subjects with deep brain stimulation of the subthalamic nucleus (STN-DBS) therapy. Methods We have evaluated all PD subjects with STN-DBS who had admitted to our outpatient polyclinic between February 2022 and March 2022. Among these patients, those who were taking levodopa therapy at least five times throughout the day and the efficiency of levodopa lasted less than 3 hours were detected. The standard levodopa therapy was switched to Madopar HBS in all patients who accepted the therapy chance and the clinical evaluation of the patients on Madopar HBS therapy was performed in the second month of the therapy. Results Ultimately, the follow-up of all four patients in whom the levodopa therapy was changed to Madopar HBS yielded a significant reduction in the "off" periods and improvement in the PSQ-39 scores. Conclusion We suggest the use of Madopar HBS in PD patients with STN-DBS surgery suffering from motor fluctuations, particularly in the subgroup with milder dyskinesias. Future study results of a large number of PD subjects with STN-DBS therapy are warranted to confirm our observations. The results of these studies may provide critical applications in clinical practice.

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel

BackgroundDysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. MethodsWe retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. ResultsA significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780–20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). ConclusionDysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Plasma Metabolic Analysis Reveals the Dysregulation of Short-Chain Fatty Acid Metabolism in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by high morbidity, high disability rate, and slow course of disease. The clinical diagnostic method of PD is complex and time-consuming, and there is no clear biomarker for clinical use. We aimed to investigate the plasma metabolites in PD and find out potential biomarkers with diagnostic ability. In the analysis of more than 40 metabolites including short-chain fatty acids, long-chain fatty acids, amino acids, and carbohydrates, the difference of short-chain fatty acids was observed. Acetic acid concentration was higher in PD than in healthy controls, and propanoic acid and 2,3,4-trihydroxybutyric acid were lower in PD. Compared with the early stage of PD, acetic acid increased significantly in the advanced stage of PD. Propanoic acid increased significantly in medicated PD compared with drug naïve PD. ROC analysis revealed acetic acid discriminated PD from healthy controls with 100% sensitivity, 88.9% specificity, and an area under the curve (AUC) of 0.981, and propanoic acid discriminated PD from healthy controls with an AUC of 0.981, 100% sensitivity, and 94.4% specificity. Acetic acid and propanoic acid may be a potential biomarker for differentiating PD from health, and the propanoic acid was evaluated as the most potential diagnostic marker because of its extremely high sensitivity and specificity.

Can kynurenine pathway be considered as a next-generation therapeutic target for Parkinson's disease? An update information

By far, no revolutionary breakthrough in the treatment of Parkinson's disease (PD) was found. It is indeed a knotty problem to select a satisfactory strategy for treating some patients with advanced stage PD. Development of novel therapeutic targets against PD has been an urgent task faced by global PD researchers. Targets in the tryptophan-kynurenine pathway (KP) were then considered. Metabolites in the KP are liposoluble. Some neurotoxic metabolites, including 3-hydroxykynurenine and its downstream 3-hydroxyanthranilic acid and quinolinic acid, are mainly produced peripherally. They can easily cross the blood-brain barrier (BBB) and exert their neurotoxic effects in the central neuron system (CNS), which is considered as a potential pathophysiological mechanism of neurodegenerative diseases. Hence, agents against the targets in the KP have two characteristics: (1) being independent from the dopaminergic system and (2) being seldom affected by the BBB. Inspiringly, one agent, namely, the inhibitor of indoleamine 2,3-dioxygenase 1, has been currently reported to present satisfactory efficacy comparable to levodopa, implying that the KP might be a potential novel target for PD. This review collected and summarized the updated information regarding the association of the KP with PD, which is helpful for understanding the clinical value of the KP in the PD scenario.

Towards Symptom-Specific Intervention Recommendation Systems.

Mobile devices and their capabilities (e.g., device sensors and human-device interactions) are increasingly being considered for use in clinical assessments and disease monitoring due to their ability to provide objective, repeatable, and more accurate measures of neurocognitive performance. These mobile-based assessments also provide a foundation for the design of intervention recommendations. The purpose of this work was to assess the benefits of various physical intervention programs as they relate to Parkinson's disease (PD), its symptoms, and stages (Hoehn and Yahr (H&Y) Stages 1-5). Ninety-five participants (n = 70 PD; n = 25 control) completed 14 tablet-based neurocognitive functional tests (e.g., motor, memory, speech, executive, and multi-function) and standardized health questionnaires. 208 symptom-specific digital features were normalized to assess the benefits of various physical intervention programs (e.g., aerobic activity, non-contact boxing, functional strength, and yoga) for individuals with PD. While previous studies have shown that physical interventions improve both motor and non-motor PD symptoms, this paper expands on previous works by mapping symptom-specific neurocognitive functionalities to specific physical intervention programs across stages of PD. For early-stage PD (e.g., H&Y Stages 1 & 2), functional strength activities provided the largest overall significant delta improvement (Δ= 0.1883; p = 0.0265), whereas aerobic activity provided the largest overall significant delta improvement (Δ= 0.2700; p = 0.0364) for advanced stages of PD (e.g., H&Y Stages 3-5). As mobile-based digital health technology allows for the collection of larger, labeled, objective datasets, new ways to analyze and interpret patterns in this data emerge which can ultimately lead to new personalized medicine programs.