Application of single wrist-wearable accelerometry for objective motor diary assessment in fluctuating Parkinson's disease.

Advanced Parkinson's disease (PD) is characterized by motor fluctuations including unpredictable oscillations remarkably impairing quality of life. Effective management and development of novel therapies for these response fluctuations largely depend on clinical rating instruments such as the widely-used PD home diary, which are associated with biases and errors. Recent advancements in digital health technologies provide user-friendly wearables that can be tailored for continuous monitoring of motor fluctuations. Their criterion validity under real-world conditions using clinical examination as the gold standard remains to be determined. We prospectively examined this validity of a wearable accelerometer-based digital Parkinson's Motor Diary (adPMD) using the Parkinson's Kinetigraph (PKG®) in an alternative application by converting its continuous data into one of the three motor categories of the PD home diary (Off, On and Dyskinetic state). Sixty-three out of 91 eligible participants with fluctuating PD (46% men, average age 66) had predefined sufficient adPMD datasets (>70% of half-hour periods) from 2 consecutive days. 92% of per-protocol assessments were completed. adPMD monitoring of daily times in motor states showed moderate validity for Off and Dyskinetic state (ICC = 0.43-0.51), while inter-rating methods agreements on half-hour-level can be characterized as poor (median Cohen's κ = 0.13-0.21). Individualization of adPMD thresholds for transferring accelerometer data into diary categories improved temporal agreements up to moderate level for Dyskinetic state detection (median Cohen's κ = 0.25-0.41). Here we report that adPMD real-world-monitoring captures daily times in Off and Dyskinetic state in advanced PD with moderate validities, while temporal agreement of adPMD and clinical observer diary data is limited.

Dyskinesia and impulsive compulsive behaviour in Parkinson's disease are not related: Insights from a study with a wearable sensor.

INTRODUCTION: Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. OBJECTIVES: To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device. METHODS: In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient's and clinician's based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson's KinetiGraph™(PKG). RESULTS: We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample. CONCLUSION: Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.

Quality of life implications for elevated trait impulsivity in people with Parkinson's disease.

BACKGROUND: Several non-motor features of Parkinson's disease (PD) are known to adversely affect patient health-related quality of life (HRQL). However, the specific impact of neuropsychiatric complications, such as impulsive behaviour, is yet to be elucidated. OBJECTIVES: The present cross-sectional, observational study aimed to investigate the effects of heightened trait impulsivity on HRQL in individuals with PD. METHODS: A total of 322 people with idiopathic PD were sequentially recruited from Movement Disorder clinics across Australia. Trait impulsivity in patients was determined by Barratt's Impulsiveness Scale Version 11 (BIS-11), and grouped into tertiles (low, medium, and high). Patient HRQL was determined by the 39-item Parkinson's Disease Questionnaire (PDQ-39), complemented by the Cambridge Behavioural Inventory-Revised (CBI-R) indicating caregivers' perception of patient HRQL. RESULTS: When total BIS-11 scores were grouped into tertiles, patient perceived and caregiver-perceived HRQL were 1.7-fold (p < .001) and 2.2-fold (p < .001) worse in the high BIS-11 group when compared to patients in the low group. Univariate analysis revealed significant associations between second-order attentional (p < .001) and non-planning (p < .001) impulsivity domains with PDQ-39 scores. When controlling for confounding demographic and clinical variables, a multivariate linear regression model revealed second-order attentional impulsivity was independently predictive of poor patient perceived HRQL (p < .001). CONCLUSION: These findings suggest that increasing trait impulsivity is significantly associated with patient perceived HRQL in PD. Improved knowledge and recognition of subclinical impulsivity may guide clinicians' treatment and reduce disease burden for patients experiencing PD symptoms.

Elevated Serum Ceruloplasmin Levels Are Associated with Higher Impulsivity in People with Parkinson's Disease.

BACKGROUND: Heightened impulsivity has been reported in a subset of people with Parkinson's disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. OBJECTIVES: To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP. METHODS: The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores. RESULTS: Serum ceruloplasmin was higher in females with PD (p < 0.001) and associated with MDS-UPDRS III, Hoehn and Yahr, and ACE-R scores (p < 0.05). When correcting for covariates, higher serum ceruloplasmin concentrations were associated with the 2nd order nonplanning impulsivity and with the 1st order self-control and cognitive complexity impulsivity domains. CONCLUSIONS: Higher serum ceruloplasmin levels are independently associated with heightened nonplanning impulsivity in PwP. Thus, serum ceruloplasmin levels may have clinical utility as a marker for heightened impulsivity in PD.

Elevated Serum Homocysteine Levels Have Differential Gender-Specific Associations with Motor and Cognitive States in Parkinson's Disease.

BACKGROUND: Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson's disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. METHODS: Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson's disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. RESULTS: People with Parkinson's disease displayed significantly elevated homocysteine levels (p < 0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson's disease (r s = 0.319, p < 0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson's disease (r s = -0.449, p < 0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). CONCLUSION: Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson's disease and poorer cognitive performance in females with Parkinson's disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

Quantitative Assessment of Cerebella Ataxia, through Automated Limb-Coordination tests.

The disabilities affecting the peripheral regions of the body can be often as a result of cerebellar damage. Tremor, poor and inaccurate coordination, and irregular movements associated with gait, balance and speech are some of the manifestations. Conventionally expert opinion determines severity of Cerebellar Ataxia (CA) and the assessment is likely to be inherently subjective. The automated versions of two commonly used tests: Finger to Nose test (FNT) and Heel to Shin Test (HST), are investigated in this paper for evaluating disability and movement deficits due to CA. Limb movements are measured using Inertial Measurement Units (IMU) that captures the disability related information, using kinematic parameters such as acceleration and angular velocity considered in both time and frequency domain. Using the Singular Spectrum Analysis (SSA), the collective dominance in the data distributions of the underlying features were observed. The dominant features were combined to substantiate the correlation with the expert clinical assessments through Linear Discriminant and Regression analysis where the classifier performance was also verified by means of cross-validation. This study found that IMU features captured characteristic movements as intention tremor in FNT and not in HST. In FNT predominantly consisting of translational movements, the rotation was a dominant feature whereas acceleration were observed to be more dominant for the case of HST.