Unified Parkinson's Disease Rating Scale Motor Research Articles

The effect of deep brain stimulation on lower extremity dexterity in people with Parkinson’s disease

Purpose To examine the effect of deep brain stimulation (DBS) on lower extremity dexterity in people with Parkinson’s disease (PwPD) and to investigate the relationship between this effect and the effect of DBS on measures of different walking characteristics, and other features of Parkinson’s disease. Materials and methods Thirty-six PwPD were included. Assessment was performed twice with DBS “on” and DBS “off” state. Results The LEDT scores of both extremities, the Unified Parkinson Disease Rating Scale-motor section (UPDRS-III), the 10-Meter Walk Test (TMWT), the Timed Up and Go Test (TUG), the Figure-of-Eight Walk Test (FEWT), and the Three-Meter Backward Walk Test (TMBWT) scores were significantly better in “on” DBS condition than “off” DBS condition. The effect of DBS on lower extremity dexterity is related to age and levodopa equivalent daily dosage (LEDD). The effect of DBS on lower extremity dexterity and the effect of DBS on the bradykinesia, TUG, the FEWT, and the TMBWT were also related. Conclusions DBS has a positive effect on lower extremity dexterity. Clinical characteristics such as age and LEDD and the effect of DBS on bradykinesia, walking with turning, curved walking, and backward walking is related with the effect of DBS on lower extremity dexterity.

Is the cingulate island sign a marker for early dementia conversion in Parkinson's disease?

To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD). We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18 F-FP-CIT PET scans. Patients with PD were classified into three groups according to the CIS ratio on early-phase 18 F-FP-CIT PET images: a PD group with CIS or high CIS ratios (PD-CIS; n = 96), a PD group with inverse CIS or low CIS ratios (PD-iCIS; n = 40), and a PD group consisting of the remaining patients with normal CIS ratios (PD-nCIS; n = 90). We compared the risk of dementia conversion within a 5-year time point between the groups. There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD-CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD-iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD-CIS group did not differ from that in the PD-iCIS and PD-nCIS groups. Meanwhile, the PD-iCIS group had a higher risk of dementia conversion than the PD-nCIS group. The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.

Striatal Dopamine Transporter Uptake, Parkinsonism, and Cognition in Alzheimer's Disease.

The correlates of motor parkinsonism in Alzheimer's disease (AD) remains controversial. We evaluated the effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD. This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET, 18 F-Florbetaben PET, 3-Tesla brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal, and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen, and substantia nigra were quantified. We investigated the relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score, and cognition using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. Path analysis and multivariable GLM for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Deep Brain Stimulation of the Subthalamic Nucleus in a Patient With X-Linked Dystonia-Parkinsonism. (P11-11.001)

<h3>Objective:</h3> N/A <h3>Background:</h3> X-linked dystonia-parkinsonism (XDP) is one of the genetic causes of generalized dystonia. Both dystonia and parkinsonism components of the disease are frequently resistant to pharmacologic treatment. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment modality, especially for dystonic manifestations of XDP. The subthalamic nucleus (STN) is a known DBS target in Parkinson disease but it is less frequently used for treatment of dystonia. In our case report we describe a patient with XDP who underwent bilateral STN DBS with notable improvement in parkinsonism and dystonia. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Our patient is a right-handed Filipino man from the island of Panay. He developed bilateral parkinsonism, blepharospasm, oromandibular and cervical dystonia at the age of 51. Diagnosis of XDP was confirmed with genetic testing. Marked improvement of Unified Parkinson Disease Rating Scale (UPDRS) motor score in response to levodopa administration was demonstrated (65 off and 36 on). His pre-DBS Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was 27.5. Bilateral GPi were initially selected as a target for DBS lead placement based on previously published data. Surgical target was subsequently changed to bilateral STN due to distortion in GPi anatomy likely secondary to long-standing disease. Medtronic Percept PC neurostimulator with Sensight DBS leads were used. There was no surgical complications. Patient had an immediate improvement in tremor, bradykinesia and rigidity after his first programming visit; antidystonic effects of stimulation became evident over the next few weeks. There was substantial improvement in limb and oromandibular dystonia and mild effect on cervical dystonia and blepharospasm. His speech clarity became better as well. His motor UPDRS and BFMDRS decreased to 21 and 19, respectively. Gait, posture, ability to perform activities of daily living significantly improved. <h3>Conclusions:</h3> The subthalamic nucleus may be considered an alternative deep brain stimulation target in patients with X-linked dystonia-parkinsonism. <b>Disclosure:</b> Dr. Redko has nothing to disclose. Brian Kopell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Brian Kopell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott Neuromodulation. Brian Kopell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Enspire DBS. Dr. Tse has nothing to disclose.

Assessment of Virtual Reality Devices as a Means of Objectively Monitoring Parkinson’s Disease (P10-11.014)

<h3>Objective:</h3> To show that consumer virtual reality (VR) devices are capable of providing statistically reliable and replicable data on treatment response in Parkinson Disease (PD). <h3>Background:</h3> Parkinson’s disease results in motor dysfunction with varying response to exogenous levodopa. Response to treatment is monitored with ratings scale such as the Unified Parkinson Disease Rating Scale (UPDRS). However, this paradigm of care results in slow response times and limited reliability. The development of technologies to assist with clinical assessments is essential to improving care. Mass market VR devices with their ability to measure movement and generate testing environments may be able to increase objectivity, validity, and monitoring frequency. <h3>Design/Methods:</h3> Individuals with levodopa responsive PD without other complicating conditions were selected (n=20). Participants were first evaluated in their off-state using the UPDRS motor scale and participated in a virtual reality assessment which mirrored the clinical exam. Hand positioning was recorded. Afterwards, levodopa was administered and individuals were reassessed clinically and with the VR device. <h3>Results:</h3> Severity of tremor decreased after levodopa administration in all assessed states with statistical significance achieved reliably in two of three states (p&lt;0.05). Bradykinesia measures improved in all three states, though statistical significance was only achieved reliably in one state. For tremor, strong correlations between various device and physician measures of tremor severity were present (r = 0.5–0.8). For bradykinesia, moderate correlations existed between the state which had achieved statistical significance in the on-off state comparison (r ~ 0.5). Patient perception surveys noted most individuals were willing to incorporate similar devices into their care. <h3>Conclusions:</h3> VR devices are can detect patient responsiveness to levodopa and device generated metrics correlate with validated physician metrics. Device use is accepted and essentially side-effect free. This study argues for the further evaluation of PD by VR devices with future focus on complex tasks. <b>Disclosure:</b> An immediate family member of Dr. Hirczy has received personal compensation for serving as an employee of Meta. Dr. Hirczy has received personal compensation in the range of $500-$4,999 for serving as a Author with Slack Enterprises. The institution of Dr. Salinas has received research support from North Texas VA Health Care System New Investigator Award.

CircEPS15, as a sponge of MIR24-3p ameliorates neuronal damage in Parkinson disease through boosting PINK1-PRKN-mediated mitophagy

ABSTRACT Despite growing evidence that has declared the importance of circRNAs in neurodegenerative diseases, the clinical significance of circRNAs in dopaminergic (DA) neuronal degeneration in the pathogenesis of Parkinson disease (PD) remains unclear. Here, we performed rRNA-depleted RNA sequencing and detected more than 10,000 circRNAs in the plasma samples of PD patients. In consideration of ROC and the correlation between Hohen-Yahr stage (H-Y stage) and Unified Parkinson Disease Rating Scale-motor score (UPDRS) of 40 PD patients, circEPS15 was selected for further research. Low expression of circEPS15 was found in PD patients and there was a negative positive correlation between the circEPS15 level and severity of PD motor symptoms, while overexpression of circEPS15 protected DA neurons against neurotoxin-induced PD-like neurodegeneration in vitro and in vivo. Mechanistically, circEPS15 acted as a MIR24-3p sponge to promote the stable expression of target gene PINK1, thus enhancing PINK1-PRKN-dependent mitophagy to eliminate damaged mitochondria and maintain mitochondrial homeostasis. Thus, circEPS15 rescued DA neuronal degeneration through the MIR24-3p-PINK1 axis-mediated improvement of mitochondrial function. This study reveals that circEPS15 exerts a critical role in participating in PD pathogenesis, and may give us an insight into the novel avenue to develop potential biomarkers and therapeutic targets for PD. Abbreviations: AAV: adeno-associated virus; DA: dopaminergic; FISH: fluorescence in situ hybridizations; HPLC: high-performance liquid chromatography; H-Y stage: Hohen-Yahr stage; LDH: lactate dehydrogenase; MMP: mitochondrial membrane potential; MPTP/p: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid; NC: negative control; PD: Parkinson disease; PINK1: PTEN induced kinase 1; PBS: phosphate-buffered saline; ROS: reactive oxygen species; SNpc: substantia nigra pars compacta; TEM: transmission electron microscopy; UPDRS: Unified Parkinson’s Disease Rating Scale-motor score

Association of GBA genotype with motor and cognitive decline in Chinese Parkinson's disease patients.

Variants in the glucocerebrosidase (GBA) gene are the most common and significant risk factor for Parkinson's disease (PD). However, the impact of GBA variants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance of GBA status on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD. The entire GBA gene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43 GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations of GBA genotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models. The estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [-0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); -0.29 (0.04) points/year; respectively]. In addition, the GBA-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [-0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); -0.07 (0.01) points/year; respectively]. GBA-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding of GBA-PD progression may help predict prognosis and improve clinical trial design.

Disease-Associated α-Synuclein Aggregates as Biomarkers of Parkinson Disease Clinical Stage.

Robust biomarkers that can mirror Parkinson disease (PD) are of great significance. In this study, we present a novel approach to investigate disease-associated α-synuclein (αSyn) aggregates as biomarkers of PD clinical stage. We combined both seed amplification assay (SAA) and ELISA to provide a quantitative test readout that reflects the clinical severity of patients with PD. To attain this goal, we initially explored the potential of our test using 2 sets of human brain homogenates (pilot and validation sets) and then verified it with 2 independent human CSF cohorts; discovery (62 patients with PD and 34 controls) and validation (49 patients with PD and 48 controls) cohorts. We showed that oligomers-specific ELISA robustly quantified SAA end product from patients with PD or dementia with Lewy bodies with high sensitivity and specificity scores (100%). Analysis also demonstrated that seeding activity could be detected earlier with oligomeric ELISA as the test readout rather than SAA alone. Of more importance, multiplexing the assays provided robust information about the patients' clinical disease stage. In the discovery cohort, levels of CSF-seeded αSyn oligomers correlated with the severity of the clinical symptoms of PD as measured by the Unified Parkinson Disease Rating Scale (UPDRS) motor (r = 0.58, p < 0.001) and Hoehn and Yahr (H&Y) scores (r = 0.43, p < 0.01). Similar correlations were observed in the validation cohort between the concentrations of CSF-seeded αSyn oligomers and both UPDRS motor (r = 0.50, p < 0.01) and H&Y scores (r = 0.49, p < 0.01). At 20 hours, receiver operating characteristic curves analysis yielded a sensitivity of 91.9% (95% CI 82.4%-96.5%) and a specificity of 85.3% (95% CI 69.8%-93.5%), with an area under the curve of 0.969 for CSF-seeded αSyn oligomers differentiating those with PD from controls in the discovery CSF cohort, whereas, a sensitivity of 80.7% (95% CI 69.1%-88.5%), a specificity of 76.5% (95% CI 60.0%-87.5%), and area under the curve of 0.860 were generated with thioflavin T maximum intensity of fluorescence at the same time point. We showed that combining SAA and ELISA assays is a more promising diagnostic tool than SAA alone, providing information about the disease stage by correlating with clinical measures of disease severity. This study provides Class III evidence that CSF-seeded αSyn oligomers can accurately discriminate patients with PD and normal controls and CSF-seeded αSyn oligomers levels correlate with PD severity.

Neuropsychiatric Burden Is a Predictor of Early Freezing and Motor Progression in Drug-Naïve Parkinson's Disease.

Neuropsychiatric symptoms (NPS) are the most common non-motor symptom in Parkinson's disease (PD). To investigate the association between the burden of NPS and motor prognosis in patients with PD. We enrolled 329 drug-naïve patients with PD, who was non-demented and followed-up≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging and neuropsychiatric inventory (NPI) scores. We performed a survival analysis and a linear mixed model analysis to assess longitudinal motor outcomes according to the NPI total score. The Kaplan-Meier analysis showed no difference in the development of levodopa-induced dyskinesia and wearing-off according to the NPI total score. However, higher burden of NPI total score was associated with earlier freezing of gait (FOG) development in the time-dependent Cox regression models after adjusting for age at symptom onset, sex, disease duration, Unified PD Rating Scale motor score, baseline Mini-Mental State Examination score, DAT activity in the posterior putamen and levodopa-equivalent daily dose (LEDD) (Hazard ratio 1.047, p = 0.002). A linear mixed model analysis revealed that patients with a higher NPI total score had a more rapid LEDD increment (NPI×time, p = 0.003). Among 52 patients with PD who eventually developed FOG during the follow-up period, there was a significant correlation between the NPI total score and time with FOG development (γ= -0.472; p = 0.001) after adjusting for confounding factors. The present study demonstrated that the severity of NPS is a predictor of early freezing and motor progression in patients with PD.

Revisiting the L-Dopa Response as a Predictor of Motor Outcomes After Deep Brain Stimulation in Parkinson's Disease.

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.

Asleep Surgery May Improve the Therapeutic Window for Deep Brain Stimulation of the Subthalamic Nucleus

ObjectiveThe effect of anesthesia type in terms of asleep vs. awake deep brain stimulation (DBS) surgery on therapeutic window (TW) has not been investigated so far. The objective of the study was to investigate whether asleep DBS surgery of the subthalamic nucleus (STN) improves TW for both directional (dDBS) and omnidirectional (oDBS) stimulation in a large single-center population. Materials and MethodsA total of 104 consecutive patients with Parkinson’s disease (PD) undergoing STN-DBS surgery (80 asleep and 24 awake) were compared regarding TW, therapeutic threshold, side effect threshold, improvement of Unified PD Rating Scale motor score (UPDRS-III) and degree of levodopa equivalent daily dose (LEDD) reduction. ResultsAsleep DBS surgery led to significantly wider TW compared to awake surgery for both dDBS and oDBS. However, dDBS further increased TW compared to oDBS in the asleep group only and not in the awake group. Clinical efficacy in terms of UPDRS-III improvement and LEDD reduction did not differ between groups. ConclusionsOur study provides first evidence for improvement of therapeutic window by asleep surgery compared to awake surgery, which can be strengthened further by dDBS. These results support the notion of preferring asleep over awake surgery but needs to be confirmed by prospective trials.

Association between freezing of gait and bone mineral density in patients with Parkinson's disease.

Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

Prevalence, risk factors, and clinical correlations of underweight in Chinese newly diagnosed and drug-naïve patients with Parkinson's disease.

Studies have shown that patients with Parkinson's disease (PD) will experience weight loss during the progression of the illness, which suggests an increased rate of underweight. However, few studies have addressed underweight in early de novo population. This study aimed to examine the prevalence, risk factors, and clinical correlations of underweight in Chinese newly diagnosed and drug-naïve patients with PD. A total of 245 inpatients with newly diagnosed PD and 213 age-, sex-, and education-matched healthy controls were enrolled in Ningbo. BMI, demographics, supine and upright blood pressure, Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) together with fasting blood glucose, low-density lipoprotein, total cholesterol, uric acid (UA), and homocysteine were collected in all subjects. Hoehn and Yahr (HY) rating and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were also measured in patients. Overall, 35 (14.3%) patients were underweight and 14 (6.6%) controls were underweight. Binary regression analyses showed that low MoCA (p = 0.035), ΔSBP and ΔDBP values (both p < 0.001) were risk factors for underweight. Furthermore, correlation analysis indicated that BMI was associated with HY grade, UPDRS motor, HAMA, HAMD, MoCA, ΔSBP, ΔDBP, and UA values, stepwise multiple regression revealed significant correlations between BMI and ΔSBP (p < 0.001), ΔDBP (p = 0.001), MoCA (p = 0.002), UPDRS motor (p = 0.005), and HAMD scores (p = 0.014). Our study showed that the prevalence of underweight was significantly higher in Chinese newly diagnosed and drug-naïve patients with PD than in the healthy population, and several clinical variables were risk factors for underweight.

Sex differences in underweight and body mass index in Chinese early de novo patients with Parkinson's disease.

ObjectiveThere have been studies investigating sex differences in clinical manifestation of Parkinson's disease (PD). However, sex differences in underweight and body mass index (BMI) in de novo PD patients lacked systematic study. We aimed to compare sex differences in clinical features and related factors of underweight and BMI in Chinese de novo PD patients.Materials and MethodsA total of 253 untreated PD inpatients and 218 controls were recruited from Ningbo. BMI, demographics, Montreal Cognitive Assessment (MoCA), supine and upright blood pressure, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), homocysteine (HCY), uric acid, glycated hemoglobin, and lipid parameters were examined. Patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and Hoehn and Yahr (HY) Rating Scale.ResultsFemale patients had a significantly lower incidence of underweight and higher BMI than male patients, and there were sex differences in serum lipids, HCY levels, and depression severity. Binary regression analysis showed that only in male patients was underweight associated with the UPDRS motor score and lower ΔSBP and ΔDBP values (all p < .05). Further multiple regression analysis indicated, in addition to the correlations between BMI and ΔSBP and ΔDBP values in both sexes (all p < .001), BMI was also associated with MoCA and lower UPDRS motor scores in male patients and lower HAMD scores in female patients.ConclusionOur study suggests that there are significant sex differences in the prevalence of underweight, BMI, and factors associated with underweight and BMI among de novo PD patients.

Cost-Effectiveness Analysis of Deep Brain Stimulation for Parkinson Disease in Taiwan

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost. A Markov decision model was constructed on the basis of a societal perspective. The Hoehn and Yahr scale and Unified PD Rating Scale motor score were used in the polytomous logistic regression model. Markov Chain Monte Carlo simulation was used to initiate the probabilistic cost-effectiveness analysis. The life-year gained (LYG) in the STN-DBS group and medication group was, respectively, 2.937 and 2.632 years at the 3-year follow-up and 7.417 and 5.971 years at the 10-year follow-up. The quality-adjusted life-year (QALY) gained in the STN-DBS and medication groups was, respectively, 1.739 and 1.220 at the 3-year follow-up and 4.189 and 2.88 at the 10-year follow-up. The incremental cost-effectiveness ratio of STN-DBS compared with medication was $147,065 per LYG and $123,436 per QALY gained at the 3-year follow-up and $36,833 and $69,033 at the 10-year follow-up, respectively. STN-DBS is an optimal strategy when the willingness to pay is $150,000 per LYG and over $90,000 per QALY gained in 3 years and when the willingness to pay is over $38,000 per LYG and over $41,000 per QALY gained in 10 years. This study provided data comparing STN-DBS and medical treatment for PD with respect to LYG and QALY gained. STN-DBS was more cost-effective in terms of LYG and QALY gained according to the current gross domestic product of Taiwan.

Aquatic Physiotherapy and Parkinson’s Disease: Effects on Functional Motor Skills

Parkinson’s Disease (PD) is a progressive disease with motor impairment, and as such requires a multidisciplinary team that includes physiotherapy. Physiotherapy can stimulate learning ability, motor recovery, neuroplasticity and neuroprotection. The aquatic physiotherapy (AP) for PD enables movements to be progressively and safely executed, reducing the risk of falls. Hence, the objective of this study is to analyze the effects of an AP program on the functional motor skills of people with PD. This is a controlled quasi-experimental clinical trial, with blind assessor. The participants were male and female, diagnosed with PD, Hoehn and Yahr stages 1 to 4 and medical certificate for AP. The exclusion criteria were: not presenting independent walking; sensorial deficit; contraindications for attending a heated pool; alterations in levodopa ingestion. The functional assessments conducted on land were: walking speed test; Five Times Sit to Stand Test; Mini BESTest, Unified Parkinson’s Disease Rating Scale (UPDRS) for activities of daily living (ADL); and motor skill parts, evaluated before, after and 4 months after AP. The aquatic assessment was conducted through the Aquatic Functional Assessment Scale (AFAS). The participants were allocated in two groups: Control Group (CG), which did not take part in the pool activities, and Experimental Group (EG), which was submitted to AP, throughout 32 twice-a-week, 50-minute-long appointments. Functional exercises were proposed to respect the principles of specificity and progression regarding complexity in the aquatic activities through aquatic motor skills learning phases. Groups and times were compared statistically. At the end of the study, the EG was composed of 11 participants and the CG 7. There were no differences between the groups at the beginning of the study. A difference was observed between groups for gait speed in evaluation 2; difference between assessment 1 and 2 for GE in the ADL and motor, as well as between assessment 2 and 3 for GE in the motor assessment. CG presented a decline from assessment 1 and 3. In the aquatic assessment, the EG had a statistical difference after the intervention. It was observed that the AP program can modify the aquatic motor skills and the land motor skills of walking speed, the UPDRS ADL and the UPDRS motor.

Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

Parkinsonian motor signs are common and disabling in older adults without Parkinson's disease (PD), but its risk factors are not completely understood. We assessed the influence of striatal dopamine levels, cerebral small vessel disease, and other factors on age-related parkinsonian motor signs in non-PD adults. Striatal dopamine transporter (DAT) binding was quantified via [11C]-CFT positron emission tomography in 87 neurologically intact adults (20-85 years, 57.47% female) with concurrent data on: Unified Parkinson's Disease Rating Scale motor (UPDRSm), white matter hyperintensities (WMH), and other risk factors (grip strength, vibratory sensitivity, cardio- and cerebro-vascular comorbidities). Sex-adjusted nonparametric models first estimated the associations of age, DAT, WMH, and other factors with UPDRSm; next, interactions of age by DAT, WMH, or other factors were tested. To quantify the influence of DAT, WMH, and other risk factors on the main association of age with UPDRSm, multivariable mediation models with bootstrapped confidence intervals (CI) were used. Older age, lower DAT, higher WMH, and worse risk factors significantly predicted worse UPDRSm (sex-adjusted p < .04 for all). DAT, but not WMH or other factors, positively and significantly interacted with age (p = .02). DAT significantly reduced the age-UPDRSm association by 30% (results of fully adjusted mediation model: indirect effect: 0.027; bootstrapped 95% CI: 0.0007, 0.074). Striatal dopamine appears to influence to some extent the relationship between age and parkinsonian signs. However, much of the variance of parkinsonian signs appears unexplained. Longitudinal studies to elucidate the multifactorial causes of this common condition of older age are warranted.

Long Term Response to Levodopa in Parkinson's Disease.

Levodopa is the most efficacious medication in controlling the motor symptoms of Parkinson's disease (PD). There continues to be a controversy as to whether levodopa remains effective after years of therapy. To assess the long-term effectiveness of levodopa in PD patients. The response to levodopa in PD patients undergoing a levodopa challenge for deep brain stimulation (DBS) surgery evaluation from June 1997 through March 2017 were evaluated. The patients were broken into four groups based on disease duration (Group I: 0- 5 years, Group II: 6- 10 years, Group III: 11- 15 years, and Group IV:≥16 years). Levodopa response was calculated based on the changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) scores in the medication ON and OFF states. A total of 361 PD patients were included. The mean age in Group I was 59.4 years with a mean disease duration of 3.9 years (n = 29), Group II was 61 years with a mean disease duration of 8.1 years (n = 131), Group III was 64 years with a mean disease duration of 12.8 years (n = 143), and IV was 66.5 years with a mean disease duration of 18.5 years (n = 58). There was a significant improvement in UPDRS motor and ADL scores after the levodopa challenge for all groups. In a subgroup of PD patients who were evaluated for DBS surgery, there was a marked improvement in UPDRS motor and ADL scores which did not decrease with disease progression.

Normalized Mutual Information of phonetic sound to distinguish the speech of Parkinson's disease.

This study has investigated the use of inter-personnel mutual information computed from the phonetic sound recordings to differentiate between Parkinson's disease (PD) and control subjects. The normalized mutual information (NMI) denotes the amount of information shared between the voice recordings of people within the same group: PD and Control. The hypothesis of this study was that within group NMI will be significantly different when compared with inter- group NMI. For each phonetic sound, the NMI was computed for every pairing of recordings for both the PD and control groups. Pearson correlation coefficient analysis was used to determine the association of NMI with clinical parameters including Unified Parkinson's Disease Rating Scale (UPDRS), Montreal cognitive assessment (MoCA) and disease duration. ANOVA test for the three phonetic sounds of control and PD subjects showed that there is significant difference between the intra-group mean NMI for the two groups (p <; 0.003) and also showed significant association with the UPDRS motor examination score, MoCA and disease duration.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms. Methods Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis. Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P 0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P 0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms. Key words: Parkinson disease; Dopamine plasma membrane transport proteins; Signs and symptoms; Positron-emission computed; Deoxyglucose