Levodopa Equivalent Daily Dose Research Articles

Early factors for predicting discontinuation to subcutaneous Apomorphine infusion in Parkinson's disease: A prospective analysis of the Thai Apomorphine Registry

IntroductionAlthough continuous subcutaneous apomorphine infusion (CSAI) is an effective therapy for Parkinson's disease (PD) with motor fluctuations, data from Asian cohorts is limited. The therapy is often discontinued due to the complexity of its delivery. MethodsFifty-one PD patients undergoing CSAI as an add-on therapy were enrolled in the Thai Apomorphine Registry, an electronic database that recorded clinical characteristics and parameters during the 14-consecutive-day titration and long-term follow-up. Factors at the time of titration were documented in order to identify predictors of long-term discontinuation. ResultsFollowing initiation, PD patients were administered a mean CSAI dose of 5.89 mg/h (SD 1.36) over a mean time of 12.28 h (SD 1.90) each day. The mean follow-up period was 626.2 days (SD 619.17). Significant reductions in UPDRS-I, II, III, and IV scores, total NMSQ score, PDQ-8 score, daily off and dyskinesia hours, Timed Up and Go test, walking step test, levodopa-equivalent daily dose, number of times a day the levodopa was taken versus pre-CSAI values were observed (p < 0.05, each). Thirty-five (68.6%) patients discontinued during the follow-up period. Relative risks of variables recorded at the time of titration that determined discontinuation of CSAI therapy were an absence of full-time caregivers, achieving a daily off hours reduction <3.5 h, and NMSQ scores at the time of CSAI titration ≥9.5 points. ConclusionIdentifying factors that predict discontinuation of CSAI at the time of its initiation may help physicians to better understand the patient's drug response and how to manage them long-term.

Stability of MDS-UPDRS Motor Subtypes Over Three Years in Early Parkinson's Disease.

Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated.Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability.Methods: Participants (n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years.Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes (p < 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [p < 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios (p < 0.05, OR 1.77, 95% CI: 1.29–2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669–0.876), sensitivity = 57.8%, and specificity = 89.7%.Conclusion: Only 50–62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.

Dizziness in Parkinson\u2019s disease patients is associated with vestibular function

Dizziness is common in Parkinson’s disease (PD) patients. It is known that orthostatic hypotension (OH) is the main cause of such dizziness, but even without OH, quite a few PD patients complain of dizziness in the clinic. It can be regarded as non-specific because most of these patients have no neurological abnormalities. We hypothesized that this type of dizziness would be associated with vestibular function, although included patients did not have clinically confirmed vestibulopathy. We studied 84 patients without OH among 121 PD patients. Their clinical features and function were compared between patients with and without dizziness. Hoehn and Yahr stage (H&Y stage), the Unified Parkinson's Disease Rating Scale (UPDRS) part III, the Korean version of the Mini-Mental State Examination (K-MMSE), education years, disease duration, total levodopa equivalent daily dose (LEDD), the presence of dizziness, the dizziness severity, and orthostatic hypotension were tested. Vestibular evoked myogenic potentials (VEMPs) were used to characterize vestibular function. Ocular (oVEMPs) and cervical (cVEMPs) were recorded. oVEMPs in the right side showed significantly reduced potentials (p = 0.016) in PD patients with dizziness, but cVEMPs did not (all ps > 0.2). Bilateral absent oVEMP responses were more common in PD patients with dizziness (p = 0.022), but the frequencies of bilateral absent cVEMP responses were not different between the dizzy and non-dizzy groups (p = 0.898). Dizziness in PD patients without orthostatic hypotension may be associated with vestibular hypofunction. Our results provide evidence that can aid clinicians when making a treatment plan for patients with dizziness. i.e., strategies to enhance reduced vestibular function may be helpful, but this suggestion remains to be evaluated.

Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients

BackgroundImpaired bioenergetics are partially involved in the pathogenesis of Parkinson's disease (PD). Phosphoglycerate kinase (PGK), an essential enzyme for glycolysis, has recently attracted attention due to its pathogenic role in PD and as a target for disease-modifying therapies. This study is aimed to evaluate the profiles of PGK activity in red blood cells (RBCs) of PD patients and controls. MethodsSixty-eight PD patients and thirty-four age-matched unrelated controls were enrolled. PGK activities of RBCs were measured by the established colorimetric assay and standardized by the same RBC samples. ResultsPGK activity of the PD group was significantly higher than that of the control group in participants aged sixty-five years or younger, whereas it was not significantly different between the two groups at any age. PGK activity was positively correlated with aging in the control group, but this was not noted in the PD group. On multivariable analysis by partial correlation in the PD group, PGK activity was negatively correlated with the specific binding ratio of dopamine transporter scintigraphy in the striatum. The levodopa-equivalent daily dose was not significantly correlated with the enzyme activity. ConclusionThe results support the following: 1) elevation of PGK activities in RBCs can be detected in relatively young PD patients and with normal aging; 2) the degree of striatonigral degeneration is associated with elevated PGK activities. These are important considerations when the PGK assay is applied as a diagnostic biomarker of PD and to therapeutically monitor PGK-enhancing treatments.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn...

Short- and long-term motor outcome ofSTN-DBS in Parkinson's Disease: focus on sex differences.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson's disease (PD) with motor complications; the contribution of sex in determining the outcome is still not understood. We included 107 patients (71 males) with PD consecutively implanted with STN-DBS at our center. We reviewed patient charts from our database and retrospectively collected demographical and clinical data at baseline and at three follow-up visits (1, 5 and 10years). We found a long-lasting effect of DBS on motor complications, despite a progressive worsening of motor performances in the ON medication condition. Bradykinesia and non-dopaminergic features seem to be the major determinant of this progression. Conversely to males, females showed a trend towards worsening in bradykinesia already at 1-year follow-up and poorer scores in non-dopaminergic features at 10-year follow-up. Levodopa Equivalent Daily Dose (LEDD) was significantly reduced after surgery compared to baseline values; however, while in males LEDD remained significantly lower than baseline even 10years after surgery, in females LEDD returned at baseline values. Males showed a sustained effect on dyskinesias, but this benefit was less clear in females; the total electrical energy delivered was consistently lower in females compared to males. The profile of adverse events did not appear to be influenced by sex. Our data suggest that there are no major differences on the motor effect of STN-DBS between males and females. However, there may be some slight differences that should be specifically investigated in the future and that may influence therapeutic decisions in the chronic follow-up.

Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson\u2019s disease

Cognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

Subthalamic and pallidal deep brain stimulation for Parkinson\u2019s disease\u2014meta-analysis of outcomes

Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson’s disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson’s Disease Rating Scale (UPDRS) III motor scores at baseline and 6–12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.

Unilateral pallidothalamic tractotomy for akinetic-rigid Parkinson's disease: a prospective open-label study.

Neurosurgical ablation is an effective treatment for medically refractory motor symptoms of Parkinson's disease (PD). A limited number of studies have reported the effect of ablation of the pallidothalamic tract for PD. In this study, the authors evaluated the safety and efficacy of unilateral pallidothalamic tractotomy for akinetic-rigid (AR)-PD. Fourteen AR-PD patients, who were enrolled in this prospective open-label study, underwent unilateral pallidothalamic tractotomy. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and Part IV (dyskinesia and dystonia) scores and levodopa equivalent daily dose (LEDD) were evaluated at baseline and at 3 and 12 months postoperatively. Of the 14 patients enrolled in the study, 4 were lost to follow-up and 10 were analyzed. The total MDS-UPDRS Part III score significantly improved from 45 ± 4.6 at baseline to 32.9 ± 4.8 at 12 months postoperatively (p = 0.005). Contralateral side rigidity and bradykinesia significantly improved from 4.4 ± 0.5 and 10.4 ± 1.5 at baseline to 1.7 ± 0.4 (p = 0.005) and 5.2 ± 1.4 (p = 0.011) at 12 months, respectively. While posture significantly improved with a 20% reduction in scores (p = 0.038), no significant improvement was found in gait (p = 0.066). Dyskinesia and dystonia were improved with a 79.2% (p = 0.0012) and 91.7% (p = 0.041) reduction in scores, respectively. No significant change was found in the LEDD. Hypophonia was noted in 2 patients, eyelid apraxia was noted in 1 patient, and a reduced response to levodopa, which resulted in an increase in the daily dose of levodopa, was noted in 3 patients. No serious permanent neurological deficits were observed. Unilateral pallidothalamic tractotomy improved contralateral side rigidity and bradykinesia, dyskinesia, and dystonia in patients with AR-PD. Clinical trial registration no.: UMIN000031138 (umin.ac.jp).

Evaluation of the effect of bilateral subthalamic nucleus deep brain stimulation on fatigue in Parkinson’s Disease as measured by the non-motor symptoms scale

Background Fatigue is a common and disabling non-motor symptom (NMS) in Parkinson’s disease (PD) patients. However, the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on fatigue has not been widely studied. Objective To determine the effect of STN DBS on fatigue in PD patients, measured by the Non-motor symptoms scale (NMSS). Methods Cross-sectional analysis of 50 patients with PD who underwent STN DBS at King’s College Hospital and Salford Royal Hospital with fatigue scores (measured by question number 4 from domain 2 (sleep/fatigue) of the NMSS as the primary outcome measure. Secondary outcome measures included the PD Sleep Scale (PDSS), Scales for Outcome in PD (SCOPA)-motor examination, activities of daily living, motor complications, Hoehn and Yahr (HY) stage and changes in Levodopa Equivalent Daily Dose (LEDD). Results 50 patients with a mean follow-up period of 1.98 ± 1.36 years were studied. Significant improvement in median fatigue scores (4.00 (0.75–9.00) to 1.00 (0.00–4.50); p = .001) was observed. In addition, improvements in question 5 (sleep maintenance and fragmentation; 8.00 (4.00–12.00) to 0.00 (0.00–4.00); p < .001) and in domain 2 total score (sleep/fatigue; 20.00 (8.75–27.25) to 6.00 (0.75–16.00); p < .001) were also significant, together with improvements in NMSS total score, SCOPA scores and HY stage (p ≤ .02). Moreover, LEDD but especially dopamine agonists LEDD was significantly reduced after DBS (310.00 (0.00–480.00) to 150.00 (0.00–300.00); p < .020). Conclusions Even though open label and not using a validated fatigue scale, this observational analysis suggest that fatigue improves significantly after STN DBS with persisting benefits at two years follow-up.

Eight-year follow-up outcome of subthalamic deep brain stimulation for Parkinson's disease: Maintenance of therapeutic efficacy with a relatively low levodopa dosage and stimulation intensity.

AimsThis follow‐up study aimed to examine the 8‐year efficacy and safety of subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD) in southern China.MethodsThe follow‐up data of 10 patients with PD undergoing STN‐DBS were analyzed. Motor symptoms were assessed before and 1, 3, 5, and 8 years after the surgery with stimulation‐on in both off‐medication (off‐med) and on‐medication (on‐med) status using the Unified Parkinson's disease Rating Scale Part III. The quality of life was assessed using the 39‐item Parkinson's Disease Questionnaire. The sleep, cognition, and emotion were evaluated using a series of nonmotor scales. Levodopa equivalent daily dose (LEDD) and stimulation parameters were recorded at each follow‐up.ResultsThe motor symptoms were improved by 50.9%, 37.7%, 36.7%, and 37.3% in 1, 3, 5, and 8 years, respectively, in the off‐med / stimulation‐on status compared with the baseline. The quality of life improved by 39.7% and 56.1% in 1 and 3 years, respectively, but declined to the preoperative level thereafter. The sleep, cognition, and emotion were mostly unchanged. LEDD reduced from 708.1 ± 172.5 mg to 330 ± 207.8 mg in 8 years. The stimulation parameters, including amplitude, pulse width, and frequency, were 2.77 ± 0.49 V, 71.3 ± 12.8 μs, and 121.5 ± 21 Hz, respectively, in 8 years.ConclusionLong‐term therapeutic efficacy of STN‐DBS could be achieved even with relatively low stimulation intensity and medication dosage for PD patients in southern China. Motor improvement and medication reduction were maintained through the 8‐year follow‐up, but improvement in quality of life lasted for only 3 years. No definite changes was found in nonmotor symptoms after STN‐DBS.

Does antiretroviral therapy alter the course of Parkinson's disease in people living with HIV?

South Africa has the world's largest antiretroviral programme which has resulted in an increase in life expectancy in persons living with HIV. Parkinson's disease (PD) is an age-related neurodegenerative disorder. No data has been published in this setting with regards to the interaction between PD and people infected with HIV. This was a retrospective study which matched two HIV non-infected PD patients to one HIV-infected patient with PD. Patients with secondary causes of Parkinsonism were excluded. Demographic, clinical and laboratory data were extracted from the charts. Hoehn and Yahr scale was used to assess PD severity. Twenty PD patients were recruited from 1 January 2008 to 31 October 2020 and were diagnosed with HIV for a median of 72 months. The median age at onset of PD was 52 years. All patients were on antiretroviral therapy. There were no statistically significant differences in the levodopa equivalent daily dose, clinical phenotype, impulse control disorders (ICDs) and frequency of a positive family history between the two groups. HIV-infected patients had a higher frequency of dopamine dysregulation syndrome. At the end of follow-up, 3 (15%) PLH-PD had moderate to severe PD compared to 16 (40%) of PD controls. The OR of having moderate to severe PD in HIV non-infected PD patients was 4. Persons living with HIV and Parkinson's disease present with PD symptoms at a younger age, progress slower to a severe stage and respond well to dopaminergic replacement therapy.

Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson’s disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.

Lateralization of Motor Signs Affects Symptom Progression in Parkinson Disease.

Background: Asymmetry of motor signs is a cardinal feature of Parkinson disease which may impact phenotypic expression.Objective: To investigate the relationship between lateralization of motor signs and symptom progression and severity during longitudinal observation for up to 4 years in a naturalistic study.Methods: We analyzed data prospectively collected during the NINDS Parkinson Disease Biomarker Project (PDBP). We defined the Movement Disorder Society Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II as the primary measure of symptom progression. Left side predominant subjects were those whose lateralized motor scores on the MDS-UPDRS part III were ≥2 points higher on the left side than on the right side of the body. Multiple regression models (controlled for age, gender, education years, ethnicity, levodopa equivalent daily dose (LEDD) at baseline, and years with PD) were used to estimate the rate of symptom progression comparing left predominant (LPD) with non-left predominant (NLPD) subjects. A sensitivity analysis was performed using the same multiple regression models in the subgroups of low (0–26) or high (>27) MDS-UPDRS II score at baseline to determine if PD severity influenced the results.Results: We included 390 participants, 177 LPD and 213 NLPD. We found that MDS-UPDRS part II progression from baseline to 48 months was faster in LPD compared to NLPD (0.6 points per year faster in LPD, p = 0.05). Additionally, the LPD group was statistically significantly worse at baseline and at 48 months in several subparts of the MDS-UPDRS and the Parkinson's Disease Questionnaire-39 (PDQ-39) mobility score. Significantly slower progression (difference of −0.8, p = 0.01) and lower score at 48 months (difference of −3.8, p = 0.003) was seen for NLPD vs. LPD in the group with lower baseline MDS-UPDRS part II score.Conclusion: Left side lateralization was associated with faster symptom progression and worse outcomes in multiple clinical domains in our cohort. Clinicians should consider using motor predominance in their counseling regarding prognosis.

A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson’s disease

BackgroundPrevious studies suggest deep brain stimulation of the subthalamic nucleus (STN-DBS) may improve olfaction and constipation in PD, using subjective measures. ObjectiveTo utilize objective measures to assess olfaction and constipation in PD following STN-DBS. MethodsIn this prospective pilot study, olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), bowel symptoms (ROME III questionnaires, daily bowel diaries, 100 mm visual analog scales for satisfaction with treatment and bowel habits), and motor manifestations of PD were evaluated before and after STN-DBS. Levodopa equivalent daily dose (LEDD) was calculated. ResultsTen patients (8 men, mean age 67.4 ± 6.0 years) with mean PD duration of 7.5 ± 3.7 years underwent bilateral STN-DBS, with mean follow-up of 3 months for all measures, except 7 months follow-up for bowel diaries. There was improvement in the Unified Parkinson’s Disease Rating Scale motor “off” scores (33.7 ± 6.7 before and 16.1 ± 10.8 after, P = 0.001). Mean UPSIT scores (20.0 ± 6.6 versus 17.5 ± 5.7, P = 0.03) worsened from severe to total hyposmia. Seven patients had baseline constipation and completed bowel diaries. There was improvement in number of complete spontaneous bowel motions (CBSM) per week (2.2 ± 1.9 before versus 4.7 ± 2.4 after, P = 0.04), satisfaction with treatment of constipation (44 ± 27 before versus 64 ± 25 after, P = 0.02), and with bowel motions (33 ± 22 before and 48 ± 20 after, P = 0.2). However, laxative use (P = 0.15) and LEDD (P = 0.15) were unchanged. ConclusionOlfaction worsened while symptoms of constipation improved but did not resolve after STN-DBS.

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.

Improving Medication Regimen Recommendation for Parkinson's Disease Using Sensor Technology.

Parkinson’s disease medication treatment planning is generally based on subjective data obtained through clinical, physician-patient interactions. The Personal KinetiGraph™ (PKG) and similar wearable sensors have shown promise in enabling objective, continuous remote health monitoring for Parkinson’s patients. In this proof-of-concept study, we propose to use objective sensor data from the PKG and apply machine learning to cluster patients based on levodopa regimens and response. The resulting clusters are then used to enhance treatment planning by providing improved initial treatment estimates to supplement a physician’s initial assessment. We apply k-means clustering to a dataset of within-subject Parkinson’s medication changes—clinically assessed by the MDS-Unified Parkinson’s Disease Rating Scale-III (MDS-UPDRS-III) and the PKG sensor for movement staging. A random forest classification model was then used to predict patients’ cluster allocation based on their respective demographic information, MDS-UPDRS-III scores, and PKG time-series data. Clinically relevant clusters were partitioned by levodopa dose, medication administration frequency, and total levodopa equivalent daily dose—with the PKG providing similar symptomatic assessments to physician MDS-UPDRS-III scores. A random forest classifier trained on demographic information, MDS-UPDRS-III scores, and PKG time-series data was able to accurately classify subjects of the two most demographically similar clusters with an accuracy of 86.9%, an F1 score of 90.7%, and an AUC of 0.871. A model that relied solely on demographic information and PKG time-series data provided the next best performance with an accuracy of 83.8%, an F1 score of 88.5%, and an AUC of 0.831, hence further enabling fully remote assessments. These computational methods demonstrate the feasibility of using sensor-based data to cluster patients based on their medication responses with further potential to assist with medication recommendations.

Cognitive phenotypes in Parkinson's disease: A latent profile analysis.

Neurocognitive disorders in Parkinson's disease (PD) are common and heterogeneous. The aim of this study was to use a data-driven method to describe different cognitive phenotypes in PD and to explore anxiety, depression, and motor disturbances across the different cognitive profiles. Latent profile analysis was applied to the neuropsychological performances of 65 patients with idiopathic PD assessed by means of a battery of tests that encompass measures of attention, memory, executive functions, social cognition, language, and visuospatial abilities. A three-cluster model produced the best solution: Cluster A (21.54%) included patients with intact cognition or with a relatively slight cognitive impairment in memory and executive functioning; Cluster B (53.85%) included patients with an intermediate level of cognitive impairment; and Cluster C (24.61%) included patients with the most severe cognitive impairment, with greater deficit compared to Cluster B in executive functioning, and, notably, in tasks with a predominantly posterior cortical basis (naming and visuospatial abilities). The three subgroups did not differ in terms of age, gender, disease duration, motor symptom severity or side of onset, levodopa equivalent daily dose, level of anxiety, or depression; however, patients from Cluster C showed greater impairment than patients from Cluster A in measures of everyday functioning. We presented a qualitative description of three distinct cognitive phenotypes emerging from a sample of 65 PD patients. The three clusters seem to be related to daily functioning but are independent from the stage of disease, motor functioning, anxiety, and depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of Progression of Parkinson's Disease on Swallowing Ability and Oral Environment.

This study investigated the impact of the severity and treatment of Parkinson's disease (PD) on the swallowing ability and oral environment of patients. Swallowing dysfunction increases the aspiration risk and may lead to poor oral health among patients with PD. We investigated the influences of PD progression and drug treatment on the swallowing ability and oral environment using simple noninvasive screening measurements. We recruited 87 patients with PD (mean age, 71.9 ± 8.0 years; mean Hoehn and Yahr score, 2.9 ± 0.9). The PD condition was assessed in each patient using the unified Parkinson's disease rating scale (UPDRS) part III, diet type and oropharyngeal function using the swallowing disturbances questionnaire (SDQ), maximum bite force (MBF), tongue pressure (TP), and oral bacterial count (OBC). Levodopa equivalent daily dose (LEDD) was also calculated for 56 participants. Based on an SDQ score of ≥11, 29.5% of patients were dysphagic, but almost all were still on a regular diet. The SDQ score was positively correlated with disease duration (rho = 0.228, p=0.047) and UPDRS part III score (rho = 0.307, p=0.007) but was negatively correlated with OBC (rho = −0.289, p=0.012). OBC was significantly higher among patients with an SDQ score of <11 (nondysphagic) (p=0.01), and the SDQ score was lower in patients with higher OBC requiring professional oral care (p=0.03). However, OBC was also negatively correlated with LEDD (rho = −0.411, p=0.004). These results indicated low self-awareness of dysphagia among the participants and an association between dysphagia and PD progression. Moreover, the oral environment could have deteriorated with swallowing dysfunction. Patients and clinicians should be aware that higher LEDD can increase xerostomia and associated deficits in oral health.

Evaluation of the Direct Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Levodopa-Induced On-Dyskinesia in Parkinson's Disease.

Objective: This study aimed to evaluate the direct anti-dyskinesia effect of deep brain stimulation (DBS) of subthalamic nucleus (STN) on levodopa-induced on-dyskinesia in Parkinson's disease (PD) patients during the early period after surgery without reducing the levodopa dosage.Methods: We retrospectively reviewed PD patients who underwent STN-DBS from January 2017 to October 2019 and enrolled patients with levodopa-induced on-dyskinesia before surgery and without a history of thalamotomy or pallidotomy. The Unified Dyskinesia Rating Scale (UDysRS) parts I+III+IV and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were monitored prior to surgery, and at the 3-month follow-up, the location of active contacts was calculated by postoperative CT–MRI image fusion to identify stimulation sites with good anti-dyskinesia effect.Results: There were 41 patients enrolled. The postoperative levodopa equivalent daily dose (LEDD) (823.1 ± 201.5 mg/day) was not significantly changed from baseline (844.6 ± 266.1 mg/day, P = 0.348), while the UDysRS on-dyskinesia subscores significantly decreased from 24 (10–58) to 0 (0–18) [median (range)] after STN stimulation (P < 0.0001). The levodopa-induced on-dyskinesia recurred in stimulation-off/medication-on state in all the 41 patients and disappeared in 39 patients when DBS stimulation was switched on at 3 months of follow-up. The active contacts which correspond to good effect for dyskinesia were located above the STN, and the mean coordinate was 13.05 ± 1.24 mm lateral, −0.13 ± 1.16 mm posterior, and 0.72 ± 0.78 mm superior to the midcommissural point.Conclusions: High-frequency electrical stimulation of the area above the STN can directly suppress levodopa-induced on-dyskinesia.