Unified Parkinson's Disease Rating Research Articles

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD). Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients. The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = -13.5; y = -15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025-voxel analysis). We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Remote levodopa challenge test in Parkinson's disease: Feasibility, reliability, validity and economic value.

The aim was to demonstrate the feasibility, reliability and validity of an in-home remote levodopa challenge test (LCT), as delivered through an online platform, for patients with Parkinson's disease (PwPD). Patients with Parkinson's disease eligible for deep brain stimulation surgery screening were enrolled. Participants sequentially received an in-home remote LCT and an in-hospital standard LCT (separated by 2.71 weeks). A modified Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III omitting rigidity and postural stability items was used in the remote LCT. The reliability of the remote LCT was evaluated using the intraclass correlation coefficient and the concurrent validity was evaluated using the Pearson's correlation coefficient r between the levodopa responsiveness of the remote and standard LCT. Out of 106 PwPD screened, 80 (75.5%) completed both the remote and standard LCT. There was a good reliability (intraclass correlation coefficient 0.81, 95% confidence interval 0.69-0.88) and a strong correlation (r = 0.84, 95% confidence interval 0.77-0.90) between the levodopa responsiveness of the remote and standard LCT. The mean cost for PwPD was estimated to be reduced by 91% by using the remote LCT. The remote LCT is feasible, reliable and valid and may reduce healthcare-related costs for PwPD and their caregivers.

Early detection of dopaminergic dysfunction and glymphatic system impairment in Parkinson's disease

PurposeThis study aimed to assess the glymphatic function and its correlation with clinical characteristics and the loss of dopaminergic neurons in Parkinson's disease (PD) using hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) combined with diffusion tensor image analysis along the perivascular space (DTI-ALPS), choroid plexus volume (CPV), and enlarged perivascular space (EPVS) volume. MethodsTwenty-five PD patients and thirty matched healthy controls (HC) participated in the study. All participants underwent 18F-fluorodopa (18F-DOPA) PET-MRI scanning. The striatal standardized uptake value ratio (SUVR), DTI-ALPS index, CPV, and EPVS volume were calculated. Furthermore, we also analysed the relationship between the DTI-ALPS index, CPV, EPVS volume and striatal SUVR as well as clinical characteristics of PD patients. ResultsPD patients demonstrated significantly lower values in DTI-ALPS (t = 3.053, p = 0.004) and larger CPV (t = 2.743, p = 0.008) and EPVS volume (t = 2.807, p = 0.008) compared to HC. In PD group, the ALPS-index was negatively correlated with the Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores (r = −0.730, p < 0.001), and positively correlated with the mean putaminal SUVR (r = 0.560, p = 0.007) and mean caudal SUVR (r = 0.459, p = 0.032). Moreover, the mean putaminal SUVR was negatively associated with the UPDRS-III scores (r = −0.544, p = 0.009). ConclusionDTI-ALPS has the potential to uncover glymphatic dysfunction in patients with PD, with this dysfunction correlating strongly with the severity of disease, together with the mean putaminal and caudal SUVR. PET- MRI can serve as a potential multimodal imaging biomarker for early-stage PD.

Changes in the correlation between substantia nigra hyperechogenicity area and Parkinson's disease severity at different Hoehn and Yahr stages.

It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

Motor progression trajectories and risk of mild cognitive impairment in Parkinson's disease: A latent class trajectory model from PPMI cohort.

Rare studies have investigated the association between heterogeneity of motor progression and risk of early cognitive impairment in Parkinson's disease (PD). In this study, we aim to identify distinct trajectories of motor progression longitudinally and investigate their impact on predicting mild cognitive impairment (MCI). A 5-year cohort including 415 PD patients at baseline was collected from the Parkinson's Progression Markers Initiative. The severity of motor symptoms was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III. The latent class trajectory model and nonlinear mixed-effects model were used to analyze and delineate the longitudinal changes in motor symptoms. Propensity score matching (PSM) was used to minimize the impact of potential confounders. Cox proportional hazard models were applied to calculate hazard ratios for MCI, and a Kaplan-Meier curve was generated using the occurrence of MCI during the follow-up as the time-to-event. Two latent trajectories were identified: a mild and remitting motor symptoms class (Class 1, 33.01%) and a severe and progressive motor symptom class (Class 2, 66.99%). Patients in Class 2 initially exhibited severe motor symptoms that worsened progressively despite receiving anti-PD medications. In comparison, patients in Class 1 exhibited milder symptoms that improved following drug therapy and a slower progression. During a 5-year follow-up, patients in Class 2 showed a higher risk of developing MCI compared to those in Class 1 before PSM (Log-Rank 28.58, p < 0.001) and after PSM (Log-Rank 8.20, p = 0.004). PD patients with severe and progressive motor symptoms are more likely to develop MCI than those with mild and stable motor symptoms.

Effect of concomitant use of esomeprazole on levodopa pharmacokinetics and clinical symptoms in patients with Parkinson's disease

BackgroundProton pump inhibitors (PPIs), which inhibit gastric acid secretion, are frequently prescribed to patients with Parkinson's disease (PD). Levodopa, the gold-standard treatment for PD, demonstrates enhanced solubility in acidic environments. Although PPIs increase gastric pH and may affect levodopa absorption, the effect of concomitant PPI use on levodopa pharmacokinetics in patients with PD remains unknown. This study aimed to investigate the effect of the concomitant use of esomeprazole, a PPI, on the pharmacokinetics of levodopa and carbidopa and clinical symptoms in patients with PD. MethodsWe prospectively enrolled 40 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and clinical symptoms before and two weeks after the concomitant use of esomeprazole. ResultsThe plasma concentrations of levodopa 30 min after concomitant oral administration of levodopa and esomeprazole were significantly lower (4.92 ± 4.10 μmol/L) than those without concomitant esomeprazole use (6.26 ± 3.75 μmol/L; p = 0.027). The plasma concentrations of carbidopa showed no significant differences with respect to concomitant esomeprazole use. Significant elevation was recorded in all subscores of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Rating Scale scores after concomitant use of esomeprazole. No significant differences were observed between Helicobacter pylori-negative and Helicobacter pylori-positive patients. Non-elderly patients (age ≤ 70 years) tended to be more susceptible to the effect of esomeprazole on levodopa pharmacokinetics and clinical symptoms. ConclusionsThe unnecessary use of PPIs should be avoided in patients with PD, especially in non-elderly patients, to improve absorption of levodopa.

Efficacy of hyperbaric oxygen therapy as an adjunct therapy in the treatment of sleep disorders among patients with Parkinson's disease: a meta-analysis.

To systematically evaluate the efficacy of hyperbaric oxygen therapy (HBOT) as an adjunct therapy for treating sleep disorders in patients with Parkinson's disease (PD). We conducted comprehensive searches in eight databases from inception through September 2023, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database. The objective was to identify randomized controlled trials (RCTs) evaluating HBOT's effectiveness in alleviating sleep disorder symptoms in PD patients as an adjunct therapy. Literature screening and data extraction were independently executed by the authors. Meta-analyses were performed using Review Manager 5.3 software, and publication bias and sensitivity analyses were assessed using Stata 17.0 software. Seven RCTs involving 461 participants were included. The findings revealed that the addition of HBOT significantly enhanced sleep efficiency (MD = 15.26, 95% CI [10.89, 19.63], p < 0.00001), increased time in bed (MD = 69.65, 95% CI [43.01, 96.30], p < 0.00001), total sleep time (MD = 75.87, 95% CI [25.42, 126.31], p = 0.003), slow-wave sleep (SWS) time (MD = 6.14, 95% CI [3.95, 8.34], p < 0.00001), and rapid eye movement sleep (REM) time (MD = 4.07, 95% CI [2.05, 6.08], p < 0.0001), and reduced awakening frequency (MD = -11.55, 95% CI [-15.42, -7.68], p < 0.00001) and sleep latency (MD = -6.60, 95% CI [-9.43, -3.89], p < 0.00001). Additionally, significant improvements were observed in the Pittsburgh Sleep Quality Index (PSQI) (MD = -2.52, 95% CI [-2.85, -2.18], p < 0.00001), Epworth Sleepiness Scale (ESS) (MD = -2.90, 95% CI [-3.34, -2.47], p < 0.00001), Unified Parkinson's Disease Rating Scale Part III (UPDRS III) (MD = -1.32, 95% CI [-2.16, -0.47], p = 0.002), and Hoehn and Yahr grading (H-Y grading) (MD = -0.15, 95% CI [-0.28, -0.01], p = 0.03). The current meta-analysis supports the efficacy of HBOT as an adjunct therapy in managing sleep disorders in PD patients. It is recommended for PD patients experiencing sleep disturbances.Systematic review registration:https://www.crd.york.ac.uk/, identifier: CRD42023462201.

Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn &amp; Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (μ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=&lt;0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p&lt;0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p&lt;0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p&lt;0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Tandem gait step-width increases more rapidly in more severely affected people with Parkinson's disease

IntroductionTandem gait performance reportedly predicts fall risk in people with Parkinson's disease (PwPD) and help distinguish PwPD from atypical parkinsonism. In a cross-sectional study, we previously showed that tandem gait step-width widens with increasing Hoehn and Yahr (H&Y) staging scores. In this longitudinal study, we aimed to determine if progression in tandem gait deficits is dependent on disease severity in PwPD. MethodsParticipants underwent an instrumented tandem gait measurement every 6 months for at least 2 years. The mean and variability of 4 tandem gait parameters were calculated at each visit: step-width, step-length, step-time, and step-velocity. The change in these parameters over time for 3 H&Y groups (stage 1, 2 and 2.5+) compared to aging controls was determined using a random coefficients regression model. The annual percent change in tandem gait parameters was correlated with initial disease features using Kendall's τB. Results66 participants were analyzed (46 PD, 20 controls). Mean step-width increased over time in an H&Y stage-dependent manner, with H&Y 2 and H&Y 2.5+ experiencing increases of 6% and 10% per year (p = 0.001 and 0.024 respectively). Annual percent-change in step-width was correlated with initial motor Unified Parkinson's Disease Rating Scale (UPDRS) scores (Kendall's τB = 0.229), total UPDRS scores (τB = 0.249), H&Y scores (τB = 0.266) and inversely correlated with Montreal Cognitive Assessment (MoCA) scores (τB = −0.209; ps ≤ 0.019). ConclusionTandem gait step-width widens over time more rapidly in more severely affected PD patients. These results suggest that tandem gait should be routinely clinically evaluated and considered in the management of imbalance in PwPD.

Fecal Microbiota Transplantation for Treatment of Parkinson Disease

Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models. To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT. This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis. Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy. The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs). The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group. FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD. ClinicalTrials.gov Identifier: NCT04854291.

Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.

Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically. Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown. Single-center retrospective cross-sectional study. The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms. Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813). DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.

NoMoFa as a new tool to evaluate the impact of deep brain stimulation on non-motor fluctuations: A new perspective

BackgroundNon-motor symptoms and non-motor fluctuations (NMF) in Parkinson's disease (PD) strongly affect health-related quality of life (HRQoL) and disability. The impact of deep brain stimulation (DBS) on NMF remains an area of uncertainty.The aim is to evaluate the impact of DBS on NMF, using the recently validated Non-Motor Fluctuation Assessment (NoMoFa), and to explore the correlation between NMF and motor symptoms, motor complications (MC), and HRQoL post-surgical improvement. MethodsWe prospectively evaluated consecutive patients undergoing subthalamic DBS (STN-DBS), at baseline and 6-months after surgery. Assessments included the NoMoFa questionnaire, the MDS-sponsored Unified Parkinson's Disease Rating Scale, and the 39-Item Parkinson's Disease Questionnaire.Pre- and post-surgical NoMoFa scores were compared using the Wilcoxon Signed rank-test. Linear regression analysis evaluated: a) the correlation between NoMoFa scores, motor and MC improvement, correcting for age, disease duration, and dopaminergic therapy reduction; b) the correlation between HRQoL and NMF improvement, correcting for age, disease duration, motor and MC improvement. ResultsTwenty patients were evaluated. Total NMF score significantly improved (44.6 %, [IQR = 18.3–100]; p = 0.022), particularly in Off condition (52.0 %, [IQR = 25.4–100]; p = 0.009); we observed strong correlation between NMF and MC improvement (Beta = 0.728; p = 0.006), mainly driven by the mitigation of unpredictable Off (Beta = 0.905; p < 0.001). Even after adjusting for potential confounders, the reduction of NMF independently correlated with increased HRQoL (Beta = 0.714; p = 0.010). ConclusionsSTN-DBS demonstrated strong beneficial effect on NMF, resulting in significant improvement of HRQoL. This underlines the importance of recognizing NMF as a significant factor to be considered in the selection of patients eligible for STN-DBS.

Influence of Depression on the Quality of Life in Patients With Parkinson's Disease in Southwest Nigeria.

Background Parkinson's disease (PD) is a chronic neurodegenerative disorder that significantly impacts patients' quality of life (QoL). Depression is a common comorbidity in patients with PD, potentially exacerbating QoL deterioration. This study aimed to assess the influence of depression on QoL in patients with PD at Ladoke Akintola University of Technology (LAUTECH), Ogbomoso, Nigeria. Methodology A cross-sectional, descriptive study design was utilized. The study included 420 patients with PD attending the Neurology Clinic at LAUTECH. A purposive sampling technique was employed to select participants. Data collection instruments included the Unified Parkinson's Disease Rating Scale (UPDRS) for PD assessment, the Hoehn and Yahr scale for PD staging, the Patient Health Questionnaire-9 (PHQ-9) for depression evaluation, and the Parkinson's Disease Questionnaire-39 (PDQ-39) for QoL assessment. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY), with descriptive and inferential statistics (Chi-square test) to determine associations, considering a P-value < 0.05 as significant. Results Among the participants, the prevalence of moderate to severe depression was 245, representing 58.81%. QoL assessment revealed that 297 (70.71%) patients with PD reported poor to very poor overall QoL. A significant association was found between the degree of depression and overall QoL (P = 0.000). Patients with severe depression reported the poorest QoL, while those with minimal to no depression reported the highest QoL scores. Conclusions Depression significantly impacts the QoL in patients with PD at LAUTECH in southwestNigeria. Addressing depression in PD management is crucial to improve patient outcomes.

Pilot Study of Acute Behavioral Effects of Pallidal Burst Stimulation in Parkinson's Disease.

Burst-patterned pallidal deep brain stimulation (DBS) in an animal model of Parkinson's disease (PD) yields significantly prolonged therapeutic benefit compared to conventional continuous DBS, but its value in patients remains unclear. The aims were to evaluate the safety and tolerability of acute (<2 hours) burst DBS in PD patients and to evaluate preliminary clinical effectiveness relative to conventional DBS. Six PD patients were studied with DBS OFF, conventional DBS, and burst DBS. Unified Parkinson's Disease Rating Scale III (UPDRS-III) and proactive inhibition (using stop-signal task) were evaluated for each condition. Burst and conventional DBS were equally tolerated without significant adverse events. Both stimulation patterns provided equivalent significant UPDRS-III reduction and increased proactive inhibition relative to DBS OFF. This pilot study supports the safety and tolerability of burst DBS, with acute effects similar to conventional DBS. Further larger-scale studies are warranted given the potential benefits of burst DBS due to decreased total energy delivery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

High-intensity interval versus moderate-intensity continuous cycling training in Parkinson's disease: a randomized trial.

Exercise training is recommended to improve the quality of life in those living with Parkinson's disease (PD); however, the optimal prescription to improve cardiorespiratory fitness and disease-related motor symptoms remains unknown. Twenty-nine participants with PD were randomly allocated to either 10 wk of high-intensity interval training (HIIT) (n = 15; 6 female) or moderate-intensity continuous training (MICT) (n = 14; 5 female). The primary outcome was the change in maximal oxygen consumption (V̇o2peak). Secondary outcomes included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score, Parkinson's Fatigue Scale (PFS)-16, resting and exercise cardiovascular measures, gait, balance, and knee extensor strength and fatigability. Exercise training increased V̇o2peak (main effect of time, P < 0.01), with a clinically meaningful difference in the change following HIIT versus MICT (Δ3.7 ± 3.7 vs. 1.7 ± 3.2 mL·kg-1·min-1, P = 0.099). The UPDRS motor score improved over time (P < 0.001) but without any differences between HIIT versus MICT (Δ-9.7 ± 1.3 vs. -8.4 ± 1.4, P = 0.51). Self-reported subjective fatigue (PFS-16) decreased over time (P < 0.01) but was similar between HIIT and MICT groups (P = 0.6). Gait, balance, blood pressure (BP), and heart rate (HR) were unchanged with training (all P > 0.09). Knee extensor strength increased over time (P = 0.03) but did not differ between HIIT versus MICT (Δ8.2 ± 5.9 vs. 11.7 ± 6.2 Nm, P = 0.69). HIIT alone increased the muscular endurance of the knee extensors during an isotonic fatigue task to failure (P = 0.04). In participants with PD, HIIT and MICT both increased V̇o2peak and led to improvements in motor symptoms and perceived fatigue; HIIT may offer the potential for larger changes in V̇o2peak and reduced knee extensor fatigability.NEW & NOTEWORTHY The optimal exercise prescription to improve cardiorespiratory fitness and disease-related motor symptoms in adults with Parkinson's disease remains unknown. In a single-center randomized trial consisting of either 10 wk of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), we found that both training modes increased V̇o2peak, with a larger clinically meaningful difference following HIIT. Both exercise modes improved motor symptoms and subjective fatigue, whereas HIIT increased the muscular endurance of the knee extensors.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid β (Aβ) from the brain. Higher Aβ levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Effects of home-based EEG neurofeedback training as a non-pharmacological intervention for Parkinson's disease

ObjectivesAberrant movement-related cortical activity has been linked to impaired motor function in Parkinson's disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. Effective non-pharmacological treatments could help reduce reliance on drugs. This experiment reports the first study of home-based electroencephalographic (EEG) neurofeedback training as a non-pharmacological candidate treatment for PD. Our primary aim was to test the feasibility of our EEG neurofeedback intervention in a home setting. MethodsSixteen people with PD received six home visits comprising symptomology self-reports, a standardised motor assessment, and a precision handgrip force production task while EEG was recorded (visits 1, 2 and 6); and 3 × 1-hr EEG neurofeedback training sessions to supress the EEG mu rhythm before initiating handgrip movements (visits 3 to 5). ResultsParticipants successfully learned to self-regulate mu activity, and this appeared to expedite the initiation of precision movements (i.e., time to reach target handgrip force off-medication pre-intervention = 628 ms, off-medication post-intervention = 564 ms). There was no evidence of wider symptomology reduction (e.g., Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III Motor Examination, off-medication pre-intervention = 29.00, off-medication post intervention = 30.07). Interviews indicated that the intervention was well-received. ConclusionBased on the significant effect of neurofeedback on movement-related cortical activity, positive qualitative reports from participants, and a suggestive benefit to movement initiation, we conclude that home-based neurofeedback for people with PD is a feasible and promising non-pharmacological treatment that warrants further research.

Investigating spatiotemporal and kinematic gait parameters in individuals with Parkinson's disease with a history of freezing of gait and exploring the effects of dopaminergic therapy on freezing of gait subtypes.

Freezing of Gait (FOG) is a prevalent and debilitating symptom in idiopathic Parkinson's disease (PD). This study evaluated spatiotemporal and kinematic gait parameters in individuals with PD with a history of FOG and explored the effects of dopaminergic therapy on FOG subtypes. One hundred and nine individuals with PD underwent clinical assessments and quantitative biomechanical measures during walking cycles before and after dopaminergic therapy. Individuals with FOG were classified into levodopa-responsive and levodopa-unresponsive groups. Individuals with FOG displayed longer disease duration and higher Unified Parkinson's Disease Rating Scale (UPDRS) II, III, IV scores, and total scores and levodopa equivalent dose, than those without FOG (all p < 0.0001). Following propensity score matching of 15 pairs based on UPDRS total score and disease duration during the off-medication state, the analysis comparing the FOG and non-FOG groups revealed no significant differences in spatiotemporal and kinematic parameters. In 39 cases of FOG, dopaminergic therapy improved gait performance in individuals with PD, enhancing spatiotemporal parameters (speed, stride length, step length, step variability) and kinematic parameters (shoulder and elbow flexion/extension range of motion (ROM), pelvic rotation, and hip abduction/adduction ROM) regardless of FOG responsiveness to dopaminergic therapy. A significant difference in trunk sway ROM (p = 0.029) remained before and after dopaminergic therapy, even after adjusting for disease duration and clinical severity. Dopaminergic therapy had varying effects on PD with FOG, improving several spatiotemporal and kinematic gait parameters but being less effective in levodopa-unresponsive cases. Quantitative biomechanical measures offer detailed insights into gait performance, aiding personalized fall risk assessment and guiding individualized rehabilitation programs.

Multi-Shared-Task Self-Supervised CNN-LSTM for Monitoring Free-Body Movement UPDRS-III Using Wearable Sensors.

The Unified Parkinson's Disease Rating Scale (UPDRS) is used to recognize patients with Parkinson's disease (PD) and rate its severity. The rating is crucial for disease progression monitoring and treatment adjustment. This study aims to advance the capabilities of PD management by developing an innovative framework that integrates deep learning with wearable sensor technology to enhance the precision of UPDRS assessments. We introduce a series of deep learning models to estimate UPDRS Part III scores, utilizing motion data from wearable sensors. Our approach leverages a novel Multi-shared-task Self-supervised Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) framework that processes raw gyroscope signals and their spectrogram representations. This technique aims to refine the estimation accuracy of PD severity during naturalistic human activities. Utilizing 526 min of data from 24 PD patients engaged in everyday activities, our methodology demonstrates a strong correlation of 0.89 between estimated and clinically assessed UPDRS-III scores. This model outperforms the benchmark set by single and multichannel CNN, LSTM, and CNN-LSTM models and establishes a new standard in UPDRS-III score estimation for free-body movements compared to recent state-of-the-art methods. These results signify a substantial step forward in bioengineering applications for PD monitoring, providing a robust framework for reliable and continuous assessment of PD symptoms in daily living settings.