Yahr Stage Research Articles

Alpha-synuclein in peripheral body fluid as a biomarker for Parkinson's disease.

Whether alpha-synuclein in peripheral body fluids can be used for the diagnosis of Parkinson's disease (PD) remains in controversy. This study evaluates diagnostic potential of alpha-synuclein for PD in various peripheral body fluids using a meta-analysis approach. Studies published before October 2022 were searched in Web of Science and PubMed databases. The results were computed using the STATA 12.0 statistical software. In plasma, PD patients exhibited elevated alpha-synuclein levels relative to healthy controls (HCs) [standard mean difference (SMD) = 0.78, 95% confidence interval (CI) = 0.42 to 1.15] with a sensitivity of 0.79 (95% CI: 0.64-0.89) and a specificity of 0.95 (95% CI: 0.90-0.98). Higher plasma alpha-synuclein levels were correlated with longer disease durations, higher Unified Parkinson's Disease Rating Scale motor scores, and higher Hoehn and Yahr stages in PD patients. Plasma neural-derived exosomal alpha-synuclein levels (SMD = 1.82, 95% CI = 0.30 to 3.35), ratio of plasma neural-derived exosomal alpha-synuclein to total alpha-synuclein (SMD = 1.26, 95% CI = 0.19 to 2.33), and erythrocytic alpha-synuclein levels were also increased in PD patients (SMD = 6.57, 95% CI = 3.55 to 9.58). In serum, there was no significant difference in alpha-synuclein levels between PD patients and HCs (SMD = 0.54, 95% CI = -0.27 to 1.34). In saliva, reduced alpha-synuclein levels were observed in PD patients (SMD = -0.85, 95% CI = -1.67 to -0.04). Alpha-synuclein levels in plasma, plasma neural-derived exosome, erythrocyte, and saliva may serve as potential biomarkers for the diagnosis of PD.

Factor analysis for construct validity of a trunk impairment scale in Parkinson's disease: a cross-sectional study.

To investigate the construct validity of the Trunk Impairment Scale (TIS), which was developed to assess trunk impairment in patients with stroke, in patients with Parkinson's disease (PD). This retrospective, cross-sectional study enrolled consecutive PD inpatients. Correlation analysis was performed to clarify whether the TIS assessment was related to other balance functions, lower extremity muscle strength, or walking ability. Factor analysis was performed to see how the background factors of TIS differ from balance function, lower limb muscle strength, and walking ability. Examining the data of 471 patients with PD, there were relationships between TIS and the Mini-Balance Evaluation Systems Test (r = 0.67), Barthel Index (r = 0.57), general lower limb extension torque (r = 0.51), two-minute walk test (r = 0.54), Hoehn and Yahr stage (r = -0.61), and Movement Disorder Society Unified Parkinson's Disease Rating Scale part III total points (r = -0.59). Factor analysis showed that TIS items were divided into three factors (an abdominal muscles and righting reflex component; a perception and verticality component; and a rotational component), differing from other scales that included clinical assessment items. The TIS can be useful for assessing the underlying trunk impairment as a basis for activities of daily living, gait function, and balance ability in patients with PD.

A machine learning model for prediction of sarcopenia in patients with Parkinson's Disease.

Patients with Parkinson's disease (PD) have an increased risk of sarcopenia which is expected to negatively affect gait, leading to poor clinical outcomes including falls. In this study, we investigated the gait patterns of patients with PD with and without sarcopenia (sarcopenia and non-sarcopenia groups, respectively) using an app-derived program and explored if gait parameters could be utilized to predict sarcopenia based on machine learning. Clinical and sarcopenia profiles were collected from patients with PD at Hoehn and Yahr (HY) stage ≤ 2. Sarcopenia was defined based on the updated criteria of the Asian Working Group for Sarcopenia. The gait patterns of the patients with and without sarcopenia were recorded and analyzed using a smartphone application. The random forest model was applied to predict sarcopenia in patients with PD. Data from 38 patients with PD were obtained, among which 9 (23.7%) were with sarcopenia. Clinical parameters were comparable between the sarcopenia and non-sarcopenia groups. Among various clinical and gait parameters, the average range of motion of the hip joint showed the highest association with sarcopenia. Based on the random forest algorithm, the combined difference in knee and ankle angles from standing still before walking to the maximum angle during walking (Kneeankle_diff), the difference between the angle when standing still before walking and the maximum angle during walking for the ankle (Ankle_dif), and the min angle of the hip joint (Hip_min) were the top three features that best predict sarcopenia. The accuracy of this model was 0.949. Using smartphone app and machine learning technique, our study revealed gait parameters that are associated with sarcopenia and that help predict sarcopenia in PD. Our study showed potential application of advanced technology in clinical research.

The impact of fatigue severity and depression level on the quality of life in individuals with Parkinson's disease in Taiwan.

Patients diagnosed with Parkinson's disease undergo alterations in physical, psychological, and social functionality, with the psychological domain being particularly predisposed to inducing fatigue and depressive symptoms. Understanding the alterations occurring within a patient's body and mind and how these influence their overall quality of life is crucial. This study sought to explore the predictive capacity of fatigue severity, the presence of depressive symptoms, and diverse demographic factors on the quality of life among individuals with Parkinson's disease. A cross-sectional correlational study was conducted at a teaching hospital in southern Taiwan. The research utilized a questionnaire survey to interview 133 study participants, focusing on the Quality of Life Scale, Depression Scale, Fatigue Severity Scale, Social Support Scale, and demographic attributes. A total of 130 valid questionnaires were obtained. The results showed that Hoehn and Yahr stage, fatigue severity, and depression status could predict quality of life, explaining 51.1% of the total variance. These findings suggest that patients at advanced Hoehn and Yahr stages, experiencing more severe fatigue, and exhibiting higher levels of depression, tended to report a lower overall quality of life. Our findings suggest that, in addition to Hoehn and Yahr stage, the severity of fatigue and levels of depression significantly impact the quality of life in individuals with Parkinson's disease. Nurses need to understand the "stressful life events" and the changes in appearance and physical function that patients with Parkinson's disease face due to chronic degenerative diseases. Hence, apart from addressing patients' physiological needs, healthcare professionals should also offer appropriate care for psychological issues, such as depressive symptoms. Encouraging patients to participate in "counseling groups" can further bolster their social support networks, enhancing their overall well-being and addressing comorbidities associated with chronic degenerative diseases.

Changes of brain structure and structural covariance networks in Parkinson's disease associated cognitive impairment.

Cognitive impairment (CI) is common in Parkinson's disease (PD). Multiple brain regions and their interactions are involved in PD associated CI. Magnetic resonance imaging (MRI) technology is a non-invasive method in investigating brain structure and inter-regional connections. In this study, by comparing cortical thickness, subcortical volume, and brain network topology properties in PD patients with and without CI, we aimed to understand the changes of brain structure and structural covariance network properties in PD associated CI. A total of 18 PD patients with CI and 33 PD patients without CI were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, Mini Mental State Examination Scale, Non-motor Symptom Rating Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were assessed. All participants underwent structural 3T MRI. Cortical thickness, subcortical volume, global and nodal network topology properties were measured. Compared with PD patients without CI, the volumes of white matter, thalamus and hippocampus were lower in PD patients with CI. And decreased whole-brain local efficiency is associated with CI in PD patients. While the cortical thickness and nodal network topology properties were comparable between PD patients with and without CI. Our findings support the alterations of brain structure and disruption of structural covariance network are involved in PD associated CI, providing a new insight into the association between graph properties and PD associated CI.

The value of consciousness coaching in Parkinson’s disease: Experiences and possible impact of holistic coaching

BackgroundPeople with a chronic condition such as Parkinson’s disease (PD) struggle with acceptance and finding meaning in life. Consciousness coaching could be a valuable addition in addressing these issues. ObjectiveWe aim to evaluate the user experiences and potential effectiveness of consciousness coaching for people with PD (PwPD). MethodsWe performed a pilot randomized controlled trial including PwPD in Hoehn & Yahr stage 1–3. People with cognitive impairments, severe psychiatric disorders, or those who did not have a clear issue to address with consciousness coaching, were excluded. PwPD were randomly allocated to either receiving 6 months of consciousness coaching in addition to usual care or to usual care alone. To explore experiences we performed semi-structured qualitative interviews with all PwPD in the intervention group. Potential effects were explored using questionnaires on quality of life, activities of daily life, self-management and non-motor symptoms at baseline and after 6 months. ResultsWe included 39 PwPD, 19 participants in the intervention group and 20 in the control group. Based on the interviews, we identified a number of themes and codes. In general PwPD experienced consciousness coaching as confronting but supportive in reaching their goals and in taking more responsibility for their lives. Quantitatively, we did not find a difference between groups for any of the outcomes. ConclusionsConsciousness coaching was considered valuable by most participants in this study and may be an interesting addition to PD treatment. We did not find any effects of the intervention on PD symptoms or quality of life.

Criteria of syndrome frailty in Parkinson´s disease

To evaluate syndrome frailty by the Fried phenotype in patients with Parkinson's disease (PD). Seventy-three patients over 65 years of age with Hoehn and Yahr stage 2-4 PD were tested for the presence of subjective criteria of the Fried phenotype of syndrome frailty: fatigue, difficulty in performing habitual activities, weight loss and objective criteria: grip strength and walking speed. The relationships of the objective criteria of Fried with indicators of age, sex, sports history, prescription of PD, the number of medications, blood pressure and MDS UPDRS part III scores, the severity of depression on the Beck scale and cognitive disorders on the MOCA were evaluated. All patients complained of fatigue, difficulties in performing habitual activities. Four people noted a decrease in body weight of more than 5 kg per year. Objective criteria of Fried were absent in 38 (51%) patients, 23 (32%) people had one objective criterion: reduced walking speed (less than 0.8 m/s) or hand strength (less than 16 kg for women and 26 kg for men), in 12 (17%) people both objective criteria were reduced. The values of objective criteria of weakness were correlated with age, sex and MDS UPDRS part III total scores. Frailty syndrome is difficult to diagnose in patients with PD due to the coincidence of complaints of the underlying disease and the syndrome. Objective criteria of the Fried phenotype suggest the presence of syndrome frailty in patients. The increase in the age of the patient, the female sex and the severity of PD are interrelated with the presence of objective criteria for the frailty of an elderly person.

Physical activity in Parkinson's disease: examining prescription sources, patterns, and the influence of quality of life and disease severity.

Limited research has explored the influence of quality of life (QoL) and disease severity on physical activity (PA) in Parkinson's disease (PD) patients, and the sources of PA prescription and advice for this population. This study aims to expand scientific knowledge on these topics. Two-hundred eleven PD patients were personally interviewed to collect data on PA levels using the International Physical Activity Questionnaire-Short Form and QoL using the Parkinson's Disease Questionnaire-8. An ad hoc questionnaire gathered information on disease severity (Hoehn and Yahr stages), PA behaviors, and PA recommendations. Weak but significant associations were found between PA levels, disease severity (r: -0.218; p = 0.004), and QoL (r: -0.244; p = 0.001). Most participants (85%) received PA counselling, predominantly from neurologists, either at diagnosis (52%) or shortly after (28%). Before PD onset, ~86% engaged in PA, decreasing to 66% post-diagnosis. Approximately 78% reported changes in PA, including reduced frequency (18.4%) and duration (32.8%), with walking as the primary activity. Disease severity and QoL significantly affect PA levels in PD patients. Diagnosis is associated with decreased PA frequency and duration, and walking is the preferred activity. Neurologists primarily provide PA advice.

Validity and Reliability of the Korean Versions of the 9- and 19-Item Wearing-Off Questionnaires in Parkinson's Disease.

The wearing-off (WO) phenomenon is the most common motor complication in advanced Parkinson's disease (PD), but its identification remains challenging. The 9- and 19-item Wearing-off Questionnaires (WOQ-9 and WOQ-19) are self-assessment tools for motor and nonmotor symptoms that are widely used for WO screening. We produced Korean versions of the WOQ-19 and WOQ-9 (K-WOQ-19 and K-WOQ-9) and investigated their validity and reliability. We used the translation-back translation method to produce K-WOQ-19 and K-WOQ-9, which were self-administered by 124 patients with PD. We conducted in-depth 10-minute interviews for confirming the presence of the WO phenomenon, and then stratified the participants into groups with and without WO. Diagnostic accuracy was assessed byanalyzing receiver operating characteristic curves. Concurrent validity was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) andthe Hoehn and Yahr stage with Spearman's rank correlation analysis. Reliability was assessedbased on test-retest Cohen's kappa (κ) values and intraclass correlation coefficients (ICCs). The optimal cutoff scores on the K-WOQ-19 and K-WOQ-9 for WO screening were 4 and 2, respectively. The test-retest ICCs of K-WOQ-19 and K-WOQ-9 were 0.943 and 0.938, respectively. Nineteen of the combined 20 items in K-WOQ-19 and K-WOQ-9 showed moderate-to-substantial agreement (κ=0.412-0.771, p<0.001). The scores on the translated scales were significantly correlated with MDS-UPDRS IV scores. K-WOQ-19 and K-WOQ-9 are reliable and valid tools for detecting WO, with optimal cutoff scores of 4 and 2, respectively.

Intercultural Translation and Application of the German Version of King’s Parkinson’s Disease Pain Questionnaire in Fluctuating Parkinson’s Disease

Background. Pain is common in Parkinson’s disease (PD) and impairs quality of life. The King’s PD pain questionnaire (KPPQ) is a standardized, reliable, and valid self‐administered questionnaire for screening of pain in PD. We developed a linguistically validated German version of the KPPQ and applied it to a cohort with fluctuating PD. Methods. The interculturally adapted German translation was performed according to internationally accepted procedures in coordination with the authors of the original publication but without further psychometric validation. After final approval by all translators and original authors, the German version was then tested for feasibility and comprehension in 30 PD patients. After final adaption, the German KPPQ together with the German quantitative KPPS were applied to an independent cohort of fluctuating PD patients within the VALIDATE‐PD study. Results. The use of the German version of the KPPQ in clinical practice or in the VALIDATE‐PD study revealed no significant problems of understanding. Sufficient datasets were available from 47 patients with motor fluctuations (24 (51%) males, 23 (49%) females; median (interquartile range (IQR)) age: 65 (58‐73) years; median (IQR) Hoehn and Yahr stage: 2.5 [2‐3]). Total pain was reported by 43 (92%) of participants with a median number of 4 (IQR: 2‐5) pain subtypes. We did not observe any associations of total pain frequency, neither with gender nor with other demographic or clinical parameters. Conclusions. The German version of the KPPQ is recommended as a questionnaire for assessing the frequency of pain and its subtypes in PD in clinical studies and/or routine care.

Nocturia in Parkinson's disease

Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy. One hundred and thirteen patients with PD of I-III Hoehn and Yahr stage (H&Y) were examined using the following scales: IPSS, including nocturia domain, UPDRS, Sch&En, PDQ-39, MMSE, FAB, BDI, STAI-S and STAI-T, PFS-16, NMSQuest, GDSS, GSRS, and orthotest. Nocturia was detected in 93 patients. It depended on the age of the patients (rS=0.345; p<0.001) and was more spread among women (p=0.002). We obtained positive correlations of nocturia (p<0.05) with: PDQ-39 (rS=0.296), H&Y (rS=0.223), UPDRS (rS=0.265) and its items (speech, walking disorders, standing up from chair, posture and postural stability), NMSQ (rS=0.318), FAB (rS= -0.359), BDI, STAI-S and STAI-T, PFS-16, gastrointestinal parameters and blood pressure in the supine position. No significant effect of dopaminergic therapy on the severity of nocturia was found. According to regression analysis (stepwise method), predictors of nocturia are depression, higher lying blood pressure, constipation and postural instability (R2=0.474). Nocturia is the most common urological symptom in patients with PD and it significantly reduces the quality of life starting from the early stages of the disease. Nocturia increases as PD progresses, it is independent of dopaminergic medications, and it is directly associated with a number of parkinsonian symptoms (postural, frontal cognitive, affective and autonomic), which are partly dopamine-resistant. This indicates the common pathogenesis of nocturia and other symptoms of PD and the significant influence of polytransmitter imbalance.

Feasibility Study of Parkinson's Speech Disorder Evaluation With Pre-Trained Deep Learning Model for Speech-to-Text Analysis.

This study investigates the feasibility of employing a pre-trained deep learning wave-to-vec model for speech-to-text analysis in individuals with speech disorders arising from Parkinson's disease (PD). A publicly available dataset containing speech recordings including the Hoehn and Yahr (H&Y) staging, Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part I, UPDRS Part II scores, and gender information from both healthy controls (HC) and those diagnosed with PD was utilized. Employing the Wav2Vec model, a speech-to-text analysis method was implemented on PD patient data. Tasks conducted included word letter classification, word match probability assessment, and analysis of speech waveform characteristics as provided by the model's output. For the dataset comprising 20 cases, among individuals with PD, the H&Y score averaged 2.50±0.67, the UPDRS II-part 5 score averaged 0.70±1.00, and the UPDRS III-part 18 score averaged 0.80±0.98. Additionally, the number of words derived from decoded text subsequent to speech recognition was evaluated, resulting in mean values of 299.10±16.79 and 259.80±93.39 for the HC and PD groups, respectively. Furthermore, the calculated degree of agreement for all syllables was based on the speech process. The accuracy for the reading sentences was observed to be 0.31 and 0.10, respectively. This study aimed to demonstrate the effectiveness of wave-to-vec in enhancing speech-to-text analysis for patients with speech disorders. The findings could pave the way for the development of clinical tools for improved diagnosis, evaluation, and communication support for this population.

Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain.

To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

Determination of optimal vibration dose to treat Parkinson's disease gait symptoms: A clinical trial

IntroductionMost people with Parkinson's disease (PD) will experience gait problems. Previous studies demonstrated improved gait and balance after vibration stimulation was applied to the feet of PD patients. However, not all study participants showed improvement, perhaps due to sub-optimal vibration stimulus. Thus far, the optimal frequency and amplitude of vibration for mitigating gait dysfunction in PD have yet to be systematically explored. This study aimed to deliver vibration to the feet of 26 people with PD gait disturbances. We hypothesized that a global frequency, amplitude, and minimum duration of vibration therapy are required to improve PD gait issues. MethodsThis was a phase Ib trial to identify optimal vibration parameters. Thirteen participants were recruited at Hoehn & Yahr (H&Y) stage II and 13 participants at stage III. Each group was randomly assigned to different frequency and amplitude settings prescribed by the central composite design methodology. Each participant received vibration for 18 min per walking session, for eight sessions spread over one week. ResultsResults showed an optimal response to treatment for frequency (Hz) and amplitude (mm) of vibration based on the Functional Ambulation Performance score for stages II and III. In the H&Y stage II group, stabilization of outcomes occurred after the 4th treatment. This stabilization was not seen in stage III participants. ConclusionsA global frequency and vibration amplitude have been identified for treating PD gait disorders. Patients with more advanced disease may require a longer duration of therapy.

The relationship between the rs6265 polymorphism of the BDNF gene and the level of serum neurotrophic factor in patients with Parkinson's disease

To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.

Experience of Physical Rehabilitation in Empowering Individuals Living with Parkinson’s Disease: A Qualitative Study Protocol

ntroduction: Life expectancy is good, patients live with certain problems (tremors, difficulty in activities of daily living, cognitive impairment, lack of balance etc). Although mainstay treatment requires pharmacological treatment and regular physiotherapy. So, the first-hand experience of physiotherapy matters in these individuals. Need of the study: The present protocol will explore the experience of individuals with Parkinson’s Disease (PD). It will help in exploring the patients’ physical and emotional experiences as they return to the community, their barriers, facilitators and also gaps they experience in their rehabilitation journey. Aim: To explore the experience of physical rehabilitation in empowering individuals with Parkinson’s Disease (PD). Materials and Methods: An open-ended interview guide was formed and validated by multidisciplinary experts. Both male and female above the age of 40 years, undergoing rehabilitation for atleast 6 months and having mild and moderate PD (Hoehn and Yahr stage I-III). No depression and anxiety is assessed on Hospital Anxiety and Depression scale (HADS); HADS-depression score=9, HAD-anxiety=8 will be recruited. It will have 17 open ended questions regarding the experiences after Physical Rehabilitation, Cognitive impairment’s, Activities of Daily Living (ADLs), Freezing, Balance, Facilitators, Barriers. Semi-structured interviews will be conducted and transcribed verbatim into English language, then entered into Qualitative Data Analysis (QDA) miner software for analysis. The interview guide is validated by the experts and obtained an Itemlevel Content Validity Index (I-CVI) of all items/questions of 0.84-1 while Scale-level Content Validity Index (S-CVI) by Average method and Universal agreement is 0.914 and 0.647, respectively. Results will be depicted in form of word clouds and code tree.

Weight loss in Parkinson's disease: A retrospective comparison between oral medication and device–assisted therapies

ObjectiveWeight loss (WL) is the most common symptom among patients with Parkinson's disease (PD) and has been reported to start several years before the diagnosis of PD. The relationship between WL and PD treatment is complex. This study aimed to characterize the impact of PD treatment on WL and find clues to establish the administration of nutrition for patients with PD. Materials and methodsEighty-two patients with PD (mean age, 58.4 ± 10.2 years; mean Hoehn and Yahr stage, 3.2 ± 0.7) were recruited. Their treatments included deep brain stimulation (DBS) therapy (n = 34), levodopa/carbidopa intestinal gel (LCIG) therapy (n = 13), and oral medication alone (n = 35). Based on the medical records, the age of onset, disease duration, treatment options, videofluoroscopic dysphagia scale, blood test results, and weight change were collected. ResultsThe median WL per year and rate of WL were −1.0 ± 2.8 kg and −1.9 ± 4.7 %, respectively. Most patients (93 %) were classified into normal nutrition and mild malnutrition groups by their CONUT scores. The median WL of the DBS group was significantly lower than that of the oral medication alone group (p < 0.01). The rate of WL showed a significant negative correlation with the age of onset (rho = −0.328, p = 0.003), but showed a significant positive correlation with the disease duration (rho = 0.231, p = 0.04). ConclusionThese results highlighted WL in the early stages of PD and suggested the need for adequate monitoring for patients undergoing device-aided therapy as well as oral medicine-treated patients with greater WL.

Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson's disease.

The course of impulse control disorders (ICD) varies in the early stage of Parkinson's disease (PD). We aimed to delineate the association between the evolution pattern of ICD and the progression of PD. A total of 321 de novo PD patients from the Parkinson's Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD. The ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions. Four early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.

DETERMINATION OF OPTIMAL VIBRATION DOSE TO TREAT PARKINSON’S DISEASE GAIT SYMPTOMS: A CLINICAL TRIAL

Abstract Most people with Parkinson’s disease (PD) will experience gait problems. Previous studies demonstrated improved gait and balance after vibration stimulation was applied to the feet of PD patients. However, not all study participants showed improvement, perhaps due to sub-optimal vibration stimulus. Thus far, the optimal frequency and amplitude of vibration for mitigating gait dysfunction in PD have yet to be systematically explored. The PDVibe2TM (Resonate Forward LLC, DE) delivered vibration to the feet of 26 people with PD gait disturbances. We hypothesized that a global frequency, amplitude, and minimum duration of vibration therapy is required to improve gait. This was a phase Ib trial to identify optimal vibration parameters. Thirteen participants were recruited at Hoehn &amp; Yahr (H&amp;Y) stage II and 13 participants at stage III. Each group was randomly assigned to different frequency and amplitude settings prescribed by the central composite design methodology. Each participant received vibration for 18 minutes per walking session, for eight sessions spread over one week. Results showed an optimal dose response to treatment for frequency and amplitude of vibration based on the Functional Ambulation Performance score for stages II and III. In the H&amp;Y stage II group, outcomes were stabilized after the 4th treatment. This stabilization was not seen in stage III participants. Global frequency and vibration amplitudes have been identified for treating PD gait disorders. Patients with more advanced Parkinson’s disease may require a longer duration of therapy.

Effects of dopaminergic treatment on inhibitory control differ across Hoehn and Yahr stages of Parkinson's disease.

Motor inhibitory control, a core component of cognitive control, is impaired in Parkinson's disease, dramatically impacting patients' abilities to implement goal-oriented adaptive strategies. A progressive loss of the midbrain's dopamine neurons characterizes Parkinson's disease and causes motor features responsive to dopaminergic treatments. Although such treatments restore motor symptoms, their impact on response inhibition is controversial. Most studies failed to show any effect of dopaminergic medicaments, although three studies found that these drugs selectively improved inhibitory control in early-stage patients. Importantly, all previous studies assessed only one domain of motor inhibition, i.e. reactive inhibition (the ability to react to a stop signal). The other domain, i.e. proactive inhibition (the ability to modulate reactive inhibition pre-emptively according to the current context), was utterly neglected. To re-examine this issue, we recruited cognitively unimpaired Parkinson's patients under dopaminergic treatment in the early (Hoehn and Yahr, 1-1.5, n = 20), intermediate (Hoehn and Yahr 2, n = 20), and moderate/advanced (Hoehn and Yahr, 2.5-3, n = 20) stages of the disease. Using a cross-sectional study design, we compared their performance on a simple reaction-time task and a stop-signal task randomly performed twice on dopaminergic medication (ON) and after medication withdrawal (OFF). Normative data were collected on 30 healthy controls. Results suggest that medication effects are stage-dependent. In Hoehn and Yahr 1-1.5 patients, drugs selectively impair reactive inhibition, leaving proactive inhibition unaffected. In the ON state, Hoehn and Yahr two patients experienced impaired proactive inhibition, whereas reactive inhibition is no longer affected, as it deteriorates even during the OFF state. By contrast, Hoehn and Yahr 2.5-3 patients exhibited less efficient reactive and proactive inhibition in the OFF state, and medication slightly improved proactive inhibition. This evidence aligns with the dopamine overdose hypothesis, indicating that drug administration may overdose intact dopamine circuitry in the earliest stages, impairing associated cognitive functions. In later stages, the progressive degeneration of dopaminergic neurons prevents the overdose and can exert some beneficial effects. Thus, our findings suggest that inhibitory control assessment might help tailor pharmacological therapy across the disease stage to enhance Parkinson's disease patients' quality of life by minimizing the hampering of inhibitory control and maximizing the reduction of motor symptoms.