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Freezing of gait (FOG) is a debilitating symptom of Parkinson disease (PD). It is episodic and variable in nature, making assessment difficult. Wearable sensors used in conjunction with specialized algorithms, such as our group's pFOG algorithm, provide objective data to better understand this phenomenon. While these methods are effective at detecting FOG retrospectively, more work is needed. The purpose of this paper is to explore how the existing pFOG algorithm can be refined to improve the detection and prediction of FOG. To accomplish this goal, previously collected data were utilized to assess the prediction ability of the current algorithm, the potency of each FOG assessment task(s) for eliciting FOG, and the maintenance of detection accuracy when modifying the sampling rate. Results illustrate that the algorithm was able to predict upcoming FOG episodes, but false positive rates were high. The Go Out and Turn-Dual Task was most potent for eliciting FOG, and the 360-Dual Task elicited the longest duration of FOG. The detection accuracy of the pFOG algorithm was maintained at a sampling rate of 60 Hz but significantly worse at 30 Hz. This work is an important step in refining the pFOG algorithm for improved clinical utility. [ABSTRACT FROM AUTHOR]

Bradykinesia is a term describing several manifestations of movement disruption caused by Parkinson's disease (PD), including movement slowing, amplitude reduction, and gradual decrease of speed and amplitude over multiple repetitions of the same movement. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves bradykinesia in patients with PD. We examined the effect of DBS on specific components of bradykinesia when applied at two locations within the STN, using signal processing techniques to identify the time course of amplitude and frequency of repeated hand pronation-supination movements performed by participants with and without PD. Stimulation at either location increased movement amplitude, increased frequency, and decreased variability, though not to the range observed in the control group. Amplitude and frequency showed decrement within trials, which was similar in PD and control groups and did not change with DBS. Decrement across trials, by contrast, differed between PD and control groups, and was reduced by stimulation. We conclude that DBS improves specific aspects of movement that are disrupted by PD, whereas it does not affect short-term decrement that could reflect muscular fatigue. NEW & NOTEWORTHY: In this study, we examined different components of bradykinesia in patients with Parkinson's disease (PD). We identified different components through signal processing techniques and their response to deep brain stimulation (DBS). We found that some components of bradykinesia respond to stimulation, whereas others do not. This knowledge advances our understanding of brain mechanisms that control movement speed and amplitude. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that remains difficult to assess. Wearable movement sensors and associated algorithms can be used to quantify FOG in laboratory settings, but the utility of such methods for real world use is unclear. We aimed to determine the suitability of our wearable sensor-based FOG assessment method for real world use by assessing its performance during in-clinic simulated real world activities. Accuracy of the sensor-based method during simulated real-world tasks was calculated using expert rated video as the gold standard. To determine feasibility for unsupervised home use, we also determined correlations between the percent of active time spent freezing (%ATSF) during unsupervised home use and in-clinic activities. Nineteen people with PD and FOG participated in this study. Results from our sensor-based method demonstrated an accuracy above 90% compared to gold-standard expert review during simulated real-world tasks. Additionally, %ATSF from our sensor-based method during unsupervised home use correlated strongly with %ATSF from our sensor-based method during in-clinic simulated real-world activities (ρ = 0.73). Accuracy values and correlation patterns suggest our method may be useful for FOG assessment in the real world. [ABSTRACT FROM AUTHOR]

Background: Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a "connected behavioral approach" that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology.Methods/design: The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity.Discussion: We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018.Trial Registration: ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original. [ABSTRACT FROM AUTHOR]

Glucocerebrosidase (GBA) mutations have been associated with Parkinson's disease in numerous studies. However, it is unknown whether the increased risk of Parkinson's disease in GBA carriers is due to a loss of glucocerebrosidase enzymatic activity. We measured glucocerebrosidase enzymatic activity in dried blood spots in patients with Parkinson's disease (n = 517) and controls (n = 252) with and without GBA mutations. Participants were recruited from Columbia University, New York, and fully sequenced for GBA mutations and genotyped for the LRRK2 G2019S mutation, the most common autosomal dominant mutation in the Ashkenazi Jewish population. Glucocerebrosidase enzymatic activity in dried blood spots was measured by a mass spectrometry-based assay and compared among participants categorized by GBA mutation status and Parkinson's disease diagnosis. Parkinson's disease patients were more likely than controls to carry the LRRK2 G2019S mutation (n = 39, 7.5% versus n = 2, 0.8%, P < 0.001) and GBA mutations or variants (seven homozygotes and compound heterozygotes and 81 heterozygotes, 17.0% versus 17 heterozygotes, 6.7%, P < 0.001). GBA homozygotes/compound heterozygotes had lower enzymatic activity than GBA heterozygotes (0.85 µmol/l/h versus 7.88 µmol/l/h, P < 0.001), and GBA heterozygotes had lower enzymatic activity than GBA and LRRK2 non-carriers (7.88 µmol/l/h versus 11.93 µmol/l/h, P < 0.001). Glucocerebrosidase activity was reduced in heterozygotes compared to non-carriers when each mutation was compared independently (N370S, P < 0.001; L444P, P < 0.001; 84GG, P = 0.003; R496H, P = 0.018) and also reduced in GBA variants associated with Parkinson's risk but not with Gaucher disease (E326K, P = 0.009; T369M, P < 0.001). When all patients with Parkinson's disease were considered, they had lower mean glucocerebrosidase enzymatic activity than controls (11.14 µmol/l/h versus 11.85 µmol/l/h, P = 0.011). Difference compared to controls persisted in patients with idiopathic Parkinson's disease (after exclusion of all GBA and LRRK2 carriers; 11.53 µmol/l/h, versus 12.11 µmol/l/h, P = 0.036) and after adjustment for age and gender (P = 0.012). Interestingly, LRRK2 G2019S carriers (n = 36), most of whom had Parkinson's disease, had higher enzymatic activity than non-carriers (13.69 µmol/l/h versus 11.93 µmol/l/h, P = 0.002). In patients with idiopathic Parkinson's, higher glucocerebrosidase enzymatic activity was associated with longer disease duration (P = 0.002) in adjusted models, suggesting a milder disease course. We conclude that lower glucocerebrosidase enzymatic activity is strongly associated with GBA mutations, and modestly with idiopathic Parkinson's disease. The association of lower glucocerebrosidase activity in both GBA mutation carriers and Parkinson's patients without GBA mutations suggests that loss of glucocerebrosidase function contributes to the pathogenesis of Parkinson's disease. High glucocerebrosidase enzymatic activity in LRRK2 G2019S carriers may reflect a distinct pathogenic mechanism. Taken together, these data suggest that glucocerebrosidase enzymatic activity could be a modifiable therapeutic target. [ABSTRACT FROM AUTHOR]

People generally select a similar speed for a given motor task, such as reaching for a cup. One well established determinant of movement time is the speed--accuracy trade-off: movement time increases with the accuracy requirement. A second possible determinant is the energetic cost of making a movement. Parkinson's disease (PD), a condition characterized by generalized movement slowing (bradykinesia), provides the opportunity to directly explore this second possibility. We compared reaching movements of patients with PD with those of control subjects in a speed--accuracy trade-off task comprising conditions of increasing difficulty. Subjects completed as many trials as necessary to make 20 movements within a required speed range (trials to criterion, Nc). Difficulty was reflected in endpoint accuracy and Nc. Patients were as accurate as control subjects in all conditions (i.e., PD did not affect the speed--accuracy trade-off). However, Nc was consistently higher in patients, indicating reluctance to move fast although accuracy was not compromised. Specifically, the dependence of Nc on movement energy cost (slope SN) was steeper in patients than in control subjects. This difference in SN suggests that bradykinesia represents an implicit decision not to move fast because of a shift in the cost/benefit ratio of the energy expenditure needed to move at normal speed. SN was less steep, but statistically significant, in control subjects, which demonstrates a role for energetic cost in the normal control of movement speed. We propose that, analogous to the established role of dopamine in explicit reward-seeking behavior, the dopaminergic projection to the striatum provides a signal for implicit "motor motivation." [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about "The Freezing of Time as a Presenting Symptom of Parkinson's Disease," by Pietro Mazzoni and Blair Ford.