Advanced Parkinson's Disease Patients Research Articles

Effects of dopaminergic therapy on sleep quality in fluctuating Parkinson's disease patients.

Sleep disorders negatively impact quality of life in Parkinson's disease (PD), yet the role of antiparkinsonian drugs on sleep quality is still unclear. We aimed to explore the correlation between sleep dysfunction and dopaminergic therapy in a large cohort of advanced PD patients. Patients consecutively evaluated for device-aided therapies eligibility were evaluated by means of the PD Sleep Scale (PDSS-2; score ≥ 18 indicates poor sleep quality), and the Epworth Sleepiness Scale (ESS score ≥ 10 indicates excessive daytime sleepiness-EDS). Binary logistic regression analysis, adjusting for age, sex, disease duration, motor impairment, and sleep drugs, was employed to evaluate the association between dopaminergic therapy and PDSS-2 and ESS scores. Analysis of covariance assessed differences in PDSS-2 and ESS scores between patients without DA, and between patients treated with low or high doses of DA (cut-off: DA-LEDD = 180mg). In a cohort of 281 patients, 66.2% reported poor sleep quality, and 34.5% reported EDS. DA treatment demonstrated twofold lower odds of reporting relevant sleep disturbances (OR 0.498; p = 0.035), while DA-LEDD, levodopa-LEDD, total LEDD, and extended-release levodopa were not associated with disturbed sleep. EDS was not influenced by dopaminergic therapy. Patients with DA intake reported significant lower PDSS-2 total score (p = 0.027) and "motor symptoms at night" domain score (p = 0.044). Patients with higher doses of DA showed lower PDSS-2 total score (p = 0.043). Our study highlights the positive influence of DA add-on treatment on sleep quality in this group of advanced fluctuating PD patients.

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.

Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Insights into neuroinflammatory mechanisms of deep brain stimulation in Parkinson's disease

Parkinson's disease, a progressive neurodegenerative disorder, involves gradual degeneration of the nigrostriatal dopaminergic pathway, leading to neuronal loss within the substantia nigra pars compacta and dopamine depletion. Molecular factors, including neuroinflammation, impaired protein homeostasis, and mitochondrial dysfunction, contribute to the neuronal loss. Deep brain stimulation, a form of neuromodulation, applies electric current through stereotactically implanted electrodes, effectively managing motor symptoms in advanced Parkinson's disease patients. Deep brain stimulation exerts intricate effects on neuronal systems, encompassing alterations in neurotransmitter dynamics, microenvironment restoration, neurogenesis, synaptogenesis, and neuroprotection. Contrary to initial concerns, deep brain stimulation demonstrates antiinflammatory effects, influencing cytokine release, glial activation, and neuronal survival.This review investigates the intricacies of deep brain stimulation mechanisms, including insertional effects, histological changes, and glial responses, and sheds light on the complex interplay between electrodes, stimulation, and the brain. This exploration delves into understanding the role of neuroinflammatory pathways and the effects of deep brain stimulation in the context of Parkinson's disease, providing insights into its neuroprotective capabilities.

Home-based monitoring of persons with advanced Parkinson’s disease using smartwatch-smartphone technology

Movement deterioration is the hallmark of Parkinson’s disease (PD), characterized by levodopa-induced motor-fluctuations (i.e., symptoms’ variability related to the medication cycle) in advanced stages. However, motor symptoms are typically too sporadically and/or subjectively assessed, ultimately preventing the effective monitoring of their progression, and thus leading to suboptimal treatment/therapeutic choices. Smartwatches (SW) enable a quantitative-oriented approach to motor-symptoms evaluation, namely home-based monitoring (HBM) using an embedded inertial measurement unit. Studies validated such approach against in-clinic evaluations. In this work, we aimed at delineating personalized motor-fluctuations’ profiles, thus capturing individual differences. 21 advanced PD patients with motor fluctuations were monitored for 2 weeks using a SW and a smartphone-dedicated app (Intel Pharma Analytics Platform). The SW continuously collected passive data (tremor, dyskinesia, level of activity using dedicated algorithms) and active data, i.e., time-up-and-go, finger tapping, hand tremor and hand rotation carried out daily, once in OFF and once in ON levodopa periods. We observed overall high compliance with the protocol. Furthermore, we observed striking differences among the individual patterns of symptoms’ levodopa-related variations across the HBM, allowing to divide our participants among four data-driven, motor-fluctuations’ profiles. This highlights the potential of HBM using SW technology for revolutionizing clinical practices.

The impact of bilateral subthalamic nucleus deep brain stimulation on dyskinesia and levodopa equivalent daily dose in advanced Parkinson’s disease

Abstract OBJECTIVE: To assess the effect of bilateral subthalamic nucleus deep brain stimulation (B/L STN DBS) on the progression of dyskinesia and the levodopa equivalent daily dose (LEDD) in advanced Parkinson’s disease (APD) patients 6 months postoperatively. METHODS: Seventeen APD patients aged 21–80 years with the minimum modified Hoen &amp; Yahr score of 2 while off medication and poor motor function underwent B/L STN DBS from January 2021 to December 2021. They were assessed preoperatively and 6 months postoperatively using the Unified dyskinesia rating scale (UDysRS) and Unified Parkinson’s Disease Rating Scale Part IV (UPDRS IV) for dyskinesia and LEDD dosage. RESULTS: Significant improvement was observed postoperatively in both UDysRS (pre-op 66.53 ± 24.59, post-op 30.88 ± 12.01; P = 0.000) and UPDRS IV (pre-op 9.24 ± 1.75, post-op 5.76 ± 1.39; P = 0.000) scores. The overall clinical improvement using UDysRS was 52.23 ± 16.23%. Each subscale of UDysRS showed significant improvement postoperatively: ON dyskinesia (pre-op 21 ± 7.7, post-op 13.76 ± 5.79; P &lt; 0.05); OFF dystonia (pre-op 8.53 ± 3.26, post-op 4.94 ± 2.70; P &lt; 0.05); impairment (face, pre-op 2.47 ± 2.52, post-op 0.29 ± 0.98, P &lt; 0.05; neck and trunk, pre-op 6.29 ± 4.55, post-op 0.59 ± 0.87, P &lt; 0.05; arms, pre-op 13.06 ± 5.86, post-op 5.76 ± 3.7, P &lt; 0.05; and legs, pre-op 7.18 ± 5.12, post-op 1.29 ± 1.57, P &lt; 0.05); and disability (pre-op 8 ± 3.46, post-op 4.24 ± 2.25; P &lt; 0.05), suggesting high clinical significance. LEDD (pre-op 673.41 ± 212.69 mg, post-op 386.82 ± 133.01 mg; P = 0.000) showed significant reduction in dosage 6 months postoperatively. LEDD reduction and dyskinesia improvement showed mild-to-moderate positive correlation (r = 0.404). CONCLUSION: B/L STN DBS helps in improving dyskinesia by reducing LEDD in APD patients.

Different associated factors of subjective cognitive complaints in patients with early and advanced Parkinson's disease.

Subjective cognitive complaints (SCCs), defined as cognitive decline reported by subjects or their informants, are common in the early stage of Parkinson's disease (PD). Previous studies have shown a significant association between SCCs and non-motor features as well as objective cognitive decline in PD patients. However, the discrepancy in SCC prevalence and SCC-related factors between patients with early PD and those with advanced PD remains poorly understood. We recruited a total of 114 and 69 early PD patients and advanced PD patients, respectively. Univariate and multivariate logistic regression analyses were performed for early PD and advanced PD patients. The prevalence of SCCs in the early PD and advanced PD groups was 60.5 and 68.1%, respectively. In the early PD group, the presence of SCCs in early PD participants was significantly associated with a higher nonmotor symptoms questionnaire (NMSQ) score (OR = 1.05, 95% CI = 1.00-1.10, p = 0.040). SCCs in the advanced PD group were related to lower attention scores (OR = 0.24, 95% CI = 0.05-0.90, p = 0.043) and lower visuospatial/executive abilities scores (OR = 0.18, 95% CI = 0.04-0.86, p = 0.032). The prevalence and SCC-related factors are distinct in early PD and advanced PD. These findings suggest that SCCs in PD patients with different disease statuses appear to have different related factors that may depend on different disease severities.

Multiculturalism and reported cognitive change in Parkinson's disease.

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

Glycated hemoglobin A1c, cerebral small vessel disease burden, and disease severity in Parkinson's disease.

Our study aimed to investigate the glucose levels in PD and controls. We also examine whether glucose control is associated with PD severity regardless of diabetic status, and test whether the correlation is mediated by cerebral small vessel disease (CSVD) burden. A total of 100 patients with idiopathic PD and 100 age- and sex-matched controls who underwent brain magnetic resonance imaging (MRI) were enrolled in this study. We collected the clinical data and blood parameters, including fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), and blood lipid. Patients with PD were divided into early (n = 61) and advanced (n = 39) subgroups, based on Hoehn and Yahr (H&Y) stages. Differences between the PD and controls, PD with and without diabetes, and between two PD subgroups were compared. CSVD markers were assessed, including lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. Multivariable logistic regressions were used to test the association between HbA1c and H&Y stages. Interaction between HbA1c and CSVD burden in relation to H&Y stages was also analyzed. PD group exhibited higher HbA1c (p < 0.001), lower high-density lipoprotein cholesterol (p < 0.001) and triglyceride (p = 0.049) than controls. Advanced PD patients showed higher HbA1c than early PD group (p = 0.022). Increasing HbA1c (OR = 1.54, 95% CI 1.03-2.32, p = 0.036) along with longer disease duration (OR = 1.14, 95% CI 1.01-1.27, p = 0.028) and higher UPDRS III score (OR = 1.07, 95% CI 1.02-1.11, p = 0.002) increased the risk of belonging to the higher H&Y stage. However, interaction between HbA1c and CSVD burden in relation to H&Y stages was not significant. HbA1c is independently associated with H&Y stages in PD, and this correlation may not be mediated by CSVD burden.

Unilateral anterior capsulotomy combined with deep brain stimulation for Parkinson's disease psychosis and motor dysfunctions

Psychosis is a frequent and debilitating non-motor symptom of Parkinson's disease (PD). This study aimed to evaluate the availability of unilateral anterior capsulotomy combined with subthalamic nucleus deep brain stimulation (STN-DBS) in managing advanced PD patients comorbid with psychosis. Five advanced PD patients with psychosis who had been treated with unilateral anterior capsulotomy combined with bilateral STN-DBS were assessed. The positive subscore of the Positive and Negative Syndrome Scale (PANSS) and the Unified Parkinson's Disease Rating Scale III (UPDRS-III) were used to assess the efficacy parameter of psychosis and the improved motor symptoms, respectively. The quality of life (QoL) was accessed by an 8-item Parkinson's disease Questionnaire (PDQ-8). Clinical outcome assessments were performed at baseline and follow-ups after one or two years. Significant improvement was observed in PD patients during follow-up after the combined treatment. The positive subscore of PANSS improved by 13.4 (5.7) (mean (SD), p = 0.006). Item P1 (delusions) and Item P3 (hallucinations) of the PANSS improved by 5.0 (0.71) (p < 0.0001) and 3.6 (0.89) (p = 0.0008), respectively. Furthermore, the motor symptoms improved by 32.4 (5.7) (UPDRS-III, p = 0.0002), and the QoL improved by 6.4 (3.8) (PDQ-8, p = 0.021). No significant side effects or complications occurred during the study. For advanced PD patients with refractory psychosis, unilateral anterior capsulotomy combined with bilateral STN-DBS improved PD psychosis and motor dysfunction, providing an effective therapeutic option for such patients.

Postural Instability and Risk of Falls in Patients with Parkinson's Disease Treated with Deep Brain Stimulation: A Stabilometric Platform Study.

Postural instability (PI) in Parkinson's disease (PD) exposes patients to an increased risk of falls (RF). While dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF remain elusive. PI and RF were assessed using a stabilometric platform in six advanced PD patients. Patients were evaluated in OFF and ON dopaminergic medication and under four DBS settings: with DBS off, DBS bilateral, and unilateral DBS of the more- or less-affected side. Our findings indicate that dopaminergic medication by itself exacerbated PI and RF, and DBS alone led to a decline in RF. No combination of medication and DBS yielded a superior improvement in postural control compared to the baseline combination of OFF medication and the DBS-off condition. Yet, for ON medication, DBS significantly improved both PI and RF. Among DBS conditions, DBS bilateral provided the most favorable outcomes, improving PI and RF in the ON medication state and presenting the smallest setbacks in the OFF state. Conversely, the more-affected side DBS was less beneficial. These preliminary results could inform therapeutic strategies for advanced PD patients experiencing postural disorders.

Holter STAT-ON™ against other tools for detecting MF in advanced Parkinson's disease: an observational study.

Different screening tools to identify advanced Parkinson's disease (APD) have emerged in recent years. Among them, wearable medical devices, such as STAT-ON™, have been proposed to help to objectively detect APD. To analyze the correlation between STAT-ON™ reports and other assessment tools to identify APD and to assess the accuracy of screening tools in APD patients, using the STAT-ON™ as the gold standard. In this retrospective, observational study, data from the University Hospital Complex of Pontevedra database on 44 patients with potential APD who wore STAT-ON™ were extracted. Data were collected according to different sources of tools for identifying APD: (1) STAT-ON™, (2) information provided by the patient, (3) questionnaire for advanced Parkinson's disease (CDEPA), (4) 5-2-1 Criteria, and (5) Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD). Considering STAT-ON™ recordings as a reference, the sensitivity, specificity, and positive and negative predictive values for each tool were calculated. The kappa index assessed the degree of agreement between the gold standard and the other instruments. Although no statistically significant association was found between STAT-ON™ recordings and any screening methods evaluated, the CDEPA questionnaire demonstrated the highest sensitivity and VPN values to detect patients with APD candidates for second-line therapy (SLT). According to the correlation analyses, MANAGE-PD demonstrated the highest degree of concordance with STAT-ON™ recordings to identify the SLT indication and to predict the SLT decision. STAT-ON™ device may be a helpful tool to detect APD and to guide treatment decisions.

A study on the correlations between acoustic speech variables and bradykinesia in advanced Parkinson's disease.

Very few studies have assessed the presence of a possible correlation between speech variables and limb bradykinesia in patients with Parkinson's disease (PD). The objective of this study was to find correlations between different speech variables and upper extremity bradykinesia under different medication conditions in advanced PD patients. Retrospective data were collected from a cohort of advanced PD patients before and after an acute levodopa challenge. Each patient was assessed with a perceptual-acoustic analysis of speech, which included several quantitative parameters [i.e., maximum phonation time (MPT) and intensity (dB)]; the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items); and a timed test (a tapping test for 20 s) to quantify upper extremity bradykinesia. Pearson's correlation coefficient was applied to find correlations between the different speech variables and the tapping rate. A total of 53 PD patients [men: 34; disease duration: 10.66 (SD 4.37) years; age at PD onset: 49.81 years (SD 6.12)] were included. Levodopa intake increased the MPT of sustained phonation (p < 0.01), but it reduced the speech rate (p = 0.05). In the defined-OFF condition, MPT of sustained phonation positively correlated with both bilateral mean (p = 0.044, r-value:0.299) and left (p = 0.033, r-value:0.314) tapping. In the defined-ON condition, the MPT correlated positively with bilateral mean tapping (p = 0.003), left tapping (p = 0.003), and right tapping (p = 0.008). This study confirms the presence of correlations between speech acoustic variables and upper extremity bradykinesia in advanced PD patients. These findings suggest common pathophysiological mechanisms.

Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson’s disease

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on speech are still debated, particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced PD patients treated with bilateral STN-DBS. Each patient was assessed before surgery through a neurological evaluation and a perceptual-acoustic analysis of speech and re-assessed in the long-term in different stimulation and drug conditions. The primary outcome was the percentage change of speech intelligibility obtained by comparing the postoperative on-stimulation/off-medication condition with the preoperative off-medication condition. Twenty-five PD patients treated with bilateral STN-DBS with a 5-year follow-up were included. In the long-term, speech intelligibility stayed at the same level as preoperative values when compared with preoperative values. STN-DBS induced a significant acute improvement of speech intelligibility (p < 0.005) in the postoperative assessment when compared to the on-stimulation/off-medication and off-stimulation/off-medication conditions. These results highlight that STN-DBS may handle speech intelligibility even in the long-term.

Music Therapy for Gait and Speech Deficits in Parkinson's Disease: A Mini-Review.

Parkinson's disease (PD) is a progressive central nervous system disease with a common motor symptom of gait disturbance in PD, which is more pronounced in the later stages. Although FDA-approved treatments, including dopaminergic pharmacotherapy, deep brain stimulation, and rehabilitation, have some benefits in improving gait dysfunction, a fair amount of advanced PD patients can develop a disability, social isolation, and high mortality and morbidity. Recently, clinicians and scientists have applied music to clinical therapy, namely music therapy. It has been used as a unique rehabilitation tool to improve PD-induced gait and speech disorders. Based on relevant studies in recent years, this paper reviews the published literature about music in treating gait disorders and speech problems in PD patients. Additionally, we discuss current studies' limitations and emphasize the future potential research fields.

Apathy in Parkinson's Disease: Clinical Patterns and Neurobiological Basis.

Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.

Clinical characteristics and outcome of COVID-19 patients with Parkinson's disease: a hospital-based case-control study in Shanghai, China.

Clinical manifestations of Parkinson's disease (PD) after Corona Virus Disease 2019 (COVID-19) infection are poorly investigated. We aimed to explore the clinical features and outcomes of hospitalized PD patients with COVID-19. A total of 48 PD patients and 96 age-and sex-matched non-PD patients were included. Demographics, clinical characteristics and outcomes were compared between two groups. PD patients with COVID-19 were elderly (76.69 ± 9.21 years) with advanced stage (H-Y stage 3-5 as 65.3%). They had less clinical symptoms (nasal obstruction, etc.), more proportions of severe/critical COVID-19 clinical classification (22.9 vs. 1.0%, p < 0.001), receiving oxygen (29.2 vs. 11.5%, p = 0.011), antibiotics (39.6 vs. 21.9%, p = 0.031) therapies, as well as longer hospitalization duration (11.39 vs. 8.32, p = 0.001) and higher mortality (8.3% vs. 1.0%, p = 0.001) relative to those without PD. Laboratory results showed that the PD group had higher white blood cell counts (6.29 vs. 5.16*109, p = 0.001), neutrophil-to-lymphocyte ratio (3.14 vs. 2.11, p < 0.001) and C-reactive protein level (12.34 vs. 3.19, p < 0.001). PD patients with COVID-19 have insidious clinical manifestation, elevated proinflammatory markers and are prone to the development of severe/critical condition, contributing to a relatively poor prognosis. Early identification and active treatment of COVID-19 are pivotal to advanced PD patients during the pandemic.

Association between Respiratory Function and Motor Function in Different Stages of Parkinson’s Disease

Introduction: Respiratory dysfunction in patients with Parkinson’s disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. Methods: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson’s disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey’s post hoc test. Results: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF_25–75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = −0.248, p = 0.046), disease duration (r = −0.276, p = 0.026), H&Y scale (r = −0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = −0.277, p = 0.025), disease duration (r = −0.291, p = 0.019), H&Y scale (r = −0.434, p = 0.0001). FEF_25–75% was negatively correlated with disease duration (r = −0.247, p = 0.047), H&Y scale (r = −0.278, p = 0.025). Conclusion: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.

Interplay between speech and gait variables in PD patients treated with STN-DBS: a long-term instrumental assessment.

To evaluate correlations between speech and gait parameters in the long-term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's Disease (PD) patients. This observational study included consecutive PD patients treated with bilateral STN-DBS. Axial symptoms were evaluated using a standardized clinical-instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented timed up and go test (iTUG) respectively. Disease motor severity was evaluated with the total score and subscores of the UPDRS part III. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. Twenty-five PD patients with a five-year median follow-up after surgery (range 3-7) were included (18 M; disease duration at surgery:10.44 [sd:4.62] years; age at surgery:58.40 [sd:5.73] years). In the off-stimulation/off-medication and on-stimulation/on-medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait whereas, in the on-stimulation/on-medication condition only, patients with the poorer voice quality were also the worse to perform sit to stand and gait phases of the iTUG. On the contrary, patients with the higher speech rate performed well the turning and walking phases of the iTUG. This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN-DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.

Serum levels of p-tau181 in patients with Parkinson’s disease

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease. Evidence has shown that phosphorylated tau-181 (p-tau181) is involved in the pathological process of PD. The goal of this study was to investigate the changes of serum phosphorylated Microtubule-associated protein tau at threonine-181 in patients with Parkinson's disease and it's correlation with disease severity, cognitive impairment and prognosis. Methods: A total of 40 patients with primary Parkinson's disease who were hospitalized or outpatient in the First Affiliated Hospital of Chongqing Medical University from July 2021 to February 2022 were selected as the study subjects. Patients with secondary Parkinson's disease, Parkinson's syndrome, stroke, Alzheimer's disease, craniocerebral surgery or trauma, severe systemic or infectious diseases, local or systemic infectious diseases, motor neurone disease or other central nervous system diseases were excluded. In addition, 35 healthy subjects with similar age and gender matching were selected as the healthy control group. Age, gender, course of disease, Hoehn-Yahr (H-Y) scale, Unified Parkinson's Disease Scale (UPDRS), and MoCA score were recorded in the Parkinson's disease group. According to the H-Y scale, PD group was divided into PD patients in the advanced stage (H-Y≤2.5, n=16) and PD patients in the advanced stage (H-Y&gt;2.5, n=24). Six months after blood sample collection, we assessed the H-Y rating and UPDRS score in the Parkinson's group again by telephone follow-up. Those with decreased or unchanged H-Y rating or total UPDRS score were divided into good prognosis group (n=25), and those with increased H-Y rating or total UPDRS score were divided into poor prognosis group (n=14). The serum p-tau181 concentration of all subjects was detected and compared by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the correlation between serum p-tau181 level and UPDRS score, MoCA score and prognosis of Parkinson's disease patients was analyzed. Results: Compared with HC, serum p-tau181 concentration in PD patients were higher, but not statistically significant (1.01[0.28-2.63]vs 0.53[0.04-3.72]ug/mL, P=0.55, P&gt;0.05). There was no significant difference in p-tau181 concentration between PD patients in early stage and PD patients in advanced stage (P=0.80 P&gt;0.05), and no significant difference in p-tau181 level between PD patients with cognitive impairment, PD patients with normal cognition and HC patients (P=0.63, p&gt;0.05). P-tau181 was not significantly correlated with disease duration (r=-0.14, P=0.37, P&gt;0.05), UPDRS score (r=0.02, P=0.89, P&gt;0.05), and MoCA score (r= 0.16, P=0.32, P &gt; 0.05). There was no significant difference in serum P-tau181 expression between good prognosis group and poor prognosis group (P=0.74, P &gt; 0.05). Conclusions: Serum expression of p-tau181 increased in PD patients, but no statistical difference was observed, and no clear correlation was found between p-tau181 and disease severity and cognitive impairment. Serum p-tau181 level in PD patients has no significant prognostic significance.