On-Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Cueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode. OBJECTIVES: We aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states. METHOD: In this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG. RESULTS: DeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67. CONCLUSIONS: DeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. © 2024 International Parkinson and Movement Disorder Society.

A meta-analysis identifies factors predicting the future development of freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is a debilitating problem that is common among many, but not all, people with Parkinson's disease (PD). Numerous attempts have been made at treating FOG to reduce its negative impact on fall risk, functional independence, and health-related quality of life. However, optimal treatment remains elusive. Observational studies have recently investigated factors that differ among patients with PD who later develop FOG, compared to those who do not. With prediction and prevention in mind, we conducted a systematic review and meta-analysis of publications through 31.12.2022 to identify risk factors. Studies were included if they used a cohort design, included patients with PD without FOG at baseline, data on possible FOG predictors were measured at baseline, and incident FOG was assessed at follow-up. 1068 original papers were identified, 38 met a-priori criteria, and 35 studies were included in the meta-analysis (n = 8973; mean follow-up: 4.1 ± 2.7 years). Factors significantly associated with a risk of incident FOG included: higher age at onset of PD, greater severity of motor symptoms, depression, anxiety, poorer cognitive status, and use of levodopa and COMT inhibitors. Most results were robust in four subgroup analyses. These findings indicate that changes associated with FOG incidence can be detected in a subset of patients with PD, sometimes as long as 12 years before FOG manifests, supporting the possibility of predicting FOG incidence. Intriguingly, some of these factors may be modifiable, suggesting that steps can be taken to lower the risk and possibly even prevent the future development of FOG.

Multidisciplinary Intensive Rehabilitation Program for People with Parkinson's Disease: Gaps between the Clinic and Real-World Mobility.

Intensive rehabilitation programs improve motor and non-motor symptoms in people with Parkinson's disease (PD), however, it is not known whether transfer to daily-living walking occurs. The effects of multidisciplinary-intensive-outpatient rehabilitation (MIOR) on gait and balance in the clinic and on everyday walking were examined. Forty-six (46) people with PD were evaluated before and after the intensive program. A 3D accelerometer placed on the lower back measured daily-living walking during the week before and after the intervention. Participants were also stratified into "responders" and "non-responders" based on daily-living-step-counts. After the intervention, gait and balance significantly improved, e.g., MiniBest scores (p < 0.001), dual-task gait speed increased (p = 0.016) and 6-minute walk distance increased (p < 0.001). Many improvements persisted after 3 months. In contrast, daily-living number of steps and gait quality features did not change in response to the intervention (p > 0.1). Only among the "responders", a significant increase in daily-living number of steps was found (p < 0.001). These findings demonstrate that in people with PD improvements in the clinic do not necessarily carry over to daily-living walking. In a select group of people with PD, it is possible to ameliorate daily-living walking quality, potentially also reducing fall risk. Nevertheless, we speculate that self-management in people with PD is relatively poor; therefore, to maintain health and everyday walking abilities, actions such as long-term engaging in physical activity and preserving mobility may be needed.

Daily-Living Freezing of Gait as Quantified Using Wearables in People With Parkinson Disease: Comparison With Self-Report and Provocation Tests.

OBJECTIVE: Freezing of gait (FOG) is an episodic, debilitating phenomenon that is common among people with Parkinson disease. Multiple approaches have been used to quantify FOG, but the relationships among them have not been well studied. In this cross-sectional study, we evaluated the associations among FOG measured during unsupervised daily-living monitoring, structured in-home FOG-provoking tests, and self-report. METHODS: Twenty-eight people with Parkinson disease and FOG were assessed using self-report questionnaires, percentage of time spent frozen (%TF) during supervised FOG-provoking tasks in the home while off and on dopaminergic medication, and %TF evaluated using wearable sensors during 1 week of unsupervised daily-living monitoring. Correlations between those 3 assessment approaches were analyzed to quantify associations. Further, based on the %TF difference between in-home off-medication testing and in-home on-medication testing, the participants were divided into those responding to Parkinson disease medication (responders) and those not responding to Parkinson disease medication (nonresponders) in order to evaluate the differences in the other FOG measures. RESULTS: The %TF during unsupervised daily living was mild to moderately correlated with the %TF during a subset of the tasks of the in-home off-medication testing but not the on-medication testing or self-report. Responders and nonresponders differed in the %TF during the personal "hot spot" task of the provoking protocol while off medication (but not while on medication) but not in the total scores of the self-report questionnaires or the measures of FOG evaluated during unsupervised daily living. CONCLUSION: The %TF during daily living was moderately related to FOG during certain in-home FOG-provoking tests in the off-medication state. However, this measure of FOG was not associated with self-report or FOG provoked in the on-medication state. These findings suggest that to fully capture FOG severity, it is best to assess FOG using a combination of all 3 approaches. IMPACT: These findings suggest that several complementary approaches are needed to provide a complete assessment of FOG severity.

Protocol for the DeFOG trial: A randomized controlled trial on the effects of smartphone-based, on-demand cueing for freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG. METHODS: Sixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., "percentage time frozen" during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology. DISCUSSION: The DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives. TRIAL REGISTRATION: Clinicaltrials.gov NCT03978507.

Multitarget Transcranial Electrical Stimulation for Freezing of Gait: A Randomized Controlled Trial.

BACKGROUND: Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal. OBJECTIVE: The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG. METHODS: Seventy-seven individuals with Parkinson's disease and FOG were enrolled in a double-blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once-weekly sessions. FOG-provoking test performance (primary outcome), functional outcomes, and self-reported FOG severity were assessed. RESULTS: Primary analyses demonstrated no advantage for tDCS in the FOG-provoking test. In secondary analyses, tDCS, compared with sham, decreased self-reported FOG severity and increased daily living step counts. Among individuals with mild-to-moderate FOG severity, tDCS improved FOG-provoking test time and self-report of FOG. CONCLUSIONS: Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory-based FOG-provoking test performance. Improvements observed in participants with mild-to-moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society.

Dopaminergic therapy and prefrontal activation during walking in individuals with Parkinson's disease: does the levodopa overdose hypothesis extend to gait?

The "levodopa-overdose hypothesis" posits that dopaminergic replacement therapy (1) increases performance on tasks that depend on the nigrostriatal-pathway (e.g., motor-control circuits), yet (2) decreases performance on tasks that depend upon the mesocorticolimbic-pathway (e.g., prefrontal cortex, PFC). Previous work in Parkinson's disease (PD) investigated this model while focusing on cognitive function. Here, we evaluated whether this model applies to gait in patients with PD and freezing of gait (FOG). Forty participants were examined in both the OFF anti-Parkinsonian medication state (hypo-dopaminergic) and ON state (hyper-dopaminergic) while walking with and without the concurrent performance of a serial subtraction task. Wireless functional near-infrared spectroscopy measured PFC activation during walking. Consistent with the "overdose-hypothesis", performance on the subtraction task decreased (p = 0.027) after dopamine intake. Moreover, the effect of walking condition on PFC activation depended on the dopaminergic state (i.e., interaction effect p = 0.001). Gait significantly improved after levodopa administration (p < 0.001). Nonetheless, PFC activation was higher (p = 0.013) in this state than in the OFF state during usual-walking. This increase in PFC activation in the ON state suggests that dopamine treatment interfered with PFC functioning. Otherwise, PFC activation, putatively a reflection of cognitive compensation, should have decreased. Moreover, in contrast to the OFF state, in the ON state, PFC activation failed to increase (p = 0.313) during dual-tasking, perhaps due to a "ceiling effect". These findings extend the "levodopa-overdose hypothesis" and suggest that it also applies to gait in PD patients. While dopaminergic therapy improves certain aspects of motor performance, optimal treatment should consider the "double-edged sword" of levodopa.

Sensor-Based and Patient-Based Assessment of Daily-Living Physical Activity in People with Parkinson's Disease: Do Motor Subtypes Play a Role?

The benefits of daily-living physical activity are clear. Nonetheless, the relationship between physical activity levels and motor subtypes of Parkinson's disease (PD), i.e., tremor dominant (TD) and postural instability gait difficulty (PIGD), have not been well-studied. It is also unclear if patient perspectives and motor symptom severity are related to objective, sensor-based assessment of daily-living activity in those subtypes. To address these questions, total daily-living physical activity was quantified in 73 patients with PD and 29 healthy controls using a 3D-accelerometer worn on the lower back for at least three days. We found that individuals with the PIGD subtype were significantly less active than healthy older adults (p = 0.007), unlike individuals with the TD subtype. Among the PIGD subtype, higher daily physical activity was negatively associated with more severe ON bradykinesia (rS = -0.499, p = 0.002), motor symptoms (higher ON MDS-UPDRS (Unified Parkinson's Disease Rating Scale motor examination)-III scores), gait difficulties (rS = -0.502, p = 0.002), motor complications (rS = 0.466, p = 0.004), and balance (rS = 0.519, p = 0.001). In contrast, among the TD subtype, disease-related characteristics were not related to daily-living physical activity. Intriguingly, physical activity was not related to self-report of ADL difficulties (scores of the MDS-UPDRS Parts I or II) in both motor subtypes. These findings highlight the importance of objective daily-living physical activity monitoring and suggest that self-report does not necessarily reflect objective physical activity levels. Furthermore, the results point to important differences in factors related to physical activity in PD motor subtypes, setting the stage for personalized treatment programs.

Using Wearable Sensors and Machine Learning to Automatically Detect Freezing of Gait during a FOG-Provoking Test.

Freezing of gait (FOG) is a debilitating motor phenomenon that is common among individuals with advanced Parkinson's disease. Objective and sensitive measures are needed to better quantify FOG. The present work addresses this need by leveraging wearable devices and machine-learning methods to develop and evaluate automated detection of FOG and quantification of its severity. Seventy-one subjects with FOG completed a FOG-provoking test while wearing three wearable sensors (lower back and each ankle). Subjects were videotaped before (OFF state) and after (ON state) they took their antiparkinsonian medications. Annotations of the videos provided the "ground-truth" for FOG detection. A leave-one-patient-out validation process with a training set of 57 subjects resulted in 84.1% sensitivity, 83.4% specificity, and 85.0% accuracy for FOG detection. Similar results were seen in an independent test set (data from 14 other subjects). Two derived outcomes, percent time frozen and number of FOG episodes, were associated with self-report of FOG. Bother derived-metrics were higher in the OFF state than in the ON state and in the most challenging level of the FOG-provoking test, compared to the least challenging level. These results suggest that this automated machine-learning approach can objectively assess FOG and that its outcomes are responsive to therapeutic interventions.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

Advantages of timing the duration of a freezing of gait-provoking test in individuals with Parkinson's disease.

Evaluating freezing of gait (FOG) and quantifying its severity in patients with Parkinson's disease (PD) is challenging; objective assessment is not sufficiently established. We aimed to improve the ability to objectively evaluate FOG severity by investigating the value of measuring the duration of the test and its components. Seventy-one patients with PD and FOG completed a previously validated FOG-provoking test. The test was performed under three conditions: (1) usual, single task; (2) dual task (walking while carrying a tray); and (3) triple task (walking while holding a tray and subtracting 7 s). FOG and festination were scored using standard procedures. We evaluated effect sizes based on both the original scoring and the test duration for the motor-cognitive cost and before and after anti-Parkinsonian medication intake. Additionally, video recording of the test and total time frozen were measured. As expected, the original test score and the test duration increased across the three conditions of the task and were higher in OFF than in the ON-medication state (p < 0.036). For motor-cognitive cost, higher effect sizes were observed for the test duration of each condition, compared to the original scoring in OFF state (0.85 vs. 0.68, respectively). Change in effect size category was more pronounced in the ON state vs. OFF (0.87 vs. 0.55, respectively). Test duration was the only independent predictor for the self-report of FOG severity and the total time frozen during the test. These findings suggest that quantifying the duration of each condition of the FOG-provoking test improves its sensitivity to medications and task complexity. Timing can be used to provide immediate, objective feedback of freezing severity, and a clear interpretation of a patient's performance.

Tossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease.

BACKGROUND: Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum. OBJECTIVES: We assessed the prevalence of sleep disturbances and nocturnal hypokinesia in early and advanced PD and their relation to nonmotor symptoms and dopaminergic medication. METHODS: A total of 305 patients with PD with diverse disease severity (Hoehn and Yahr [H&Y] stage 1 = 47, H&Y stage 2 = 181, H&Y stage 3 = 77) and 205 healthy controls continuously wore a tri-axial accelerometer on the lower back for at least 2 days. Lying, turning, and upright -time at night were extracted from the acceleration signals. Percent upright time and nighttime walking were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed were used to evaluate nocturnal movements. RESULTS: Nocturnal lying time was similar among all groups (healthy controls, 7.5 ± 1.2 hours; H&Y stage 1, 7.3 ± 0.9 hours; H&Y stage 2, 7.2 ± 1.3 hours; H&Y stage 3, 7.4 ± 1.6 hours; P = 0.501). However, patients with advanced PD had more upright periods, whereas the number and velocity of their turns were reduced (P ≤ 0.021). Recently diagnosed patients (<1 year from diagnosis) were similar to controls in the number of nocturnal turns (P = 0.148), but showed longer turning time (P = 0.001) and reduced turn magnitude (P = 0.002). Reduced nocturnal movements were associated with increased PD motor severity and worse dysautonomia and cognition and with dopaminergic medication. CONCLUSIONS: Using wearable sensors for continuous monitoring of movement at night may offer an unbiased measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. © 2020 International Parkinson and Movement Disorder Society.

Depressive symptoms may increase the risk of the future development of freezing of gait in patients with Parkinson's disease: Findings from a 5-year prospective study.

INTRODUCTION: Prospective studies identifying predictors of freezing of gait (FOG) in Parkinson's disease (PD) are limited. We aim to explore which symptoms are associated with future development of FOG in non-freezers. METHODS: Fifty-seven PD patients without FOG at baseline were re-evaluated after a mean of five years. At baseline, disease severity [Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], gait under single and dual-tasking, balance, cognition and other non-motor symptoms were assessed. The new-FOG-questionnaire (NFOG-Q) determined FOG. Multivariate binary logistic regression determined independent predictors of FOG. RESULTS: At follow-up, 26 subjects (46%) had FOG while 31 remained non-freezers. At baseline, non-freezers (FOG-) and future freezers (FOG+) were similar (p > 0.10) with respect to age, gender, disease duration, dopaminergic medications, and cognitive function. However, FOG + had significantly worse scores on the Geriatric Depression Scale (GDS) (FOG+:5.2 ± 3.7; FOG-:2.4 ± 2.0, p = 0.005), PDQ-39, the NMS-questionnaire, UPDRS-part I, UPDRS-part III (off), and the Berg Balance Scale. In binary logistic regression, GDS, gait speed and UPDRS-III (on vs. off) were the only significant independent predictors of future FOG (GDS: OR = 10.93, p = 0.003, ΔUPDRS-III: OR = 1.34, p = 0.006). Moreover, 80% of the subjects who had marked depressive symptoms at baseline (GDS≥5) developed FOG at follow-up. In contrast, only 27% of those with few depressive symptoms at baseline became freezers (p < 0.001). CONCLUSIONS: Depressive symptoms apparently precede the development of FOG. While elucidation of the relationship between depression and FOG needs further study, our findings offer another perspective regarding the pathophysiology of FOG and may help clinicians to estimate the risk of developing this debilitating phenomenon.

The transition between turning and sitting in patients with Parkinson's disease: A wearable device detects an unexpected sequence of events.

BACKGROUND: When older adults turn to sit, about 80% of the subjects complete the turn before starting to sit i.e., a distinct-strategy, while in about 20%, part of the turning and sitting take place concurrently, i.e., an overlapping-strategy. A prolonged duration of the separation between tasks in the distinct-strategy (D-interval) and a prolonged duration of the overlap interval in overlapping-strategy (O-interval) are related to worse motor symptoms and poorer cognition. In the present study, we evaluated what strategy is employed by patients with Parkinson's disease (PD) when they transition from turning to sitting. METHODS: 96 participants with PD performed turn to sit as part of the Timed Up and Go test, both with and without medications, while wearing a body-fixed sensor. We quantified the turn-to-sit transition and determined which strategy (distinct or overlapping) was employed. We then stratified the cases and used regression models adjusted for age, gender, height, and weight to examine the associations of the D-interval or O-interval with parkinsonian features and cognition. RESULTS: Most patients (66%) employed the overlapping-strategy, both off and on anti-parkinsonian medications. Longer O-intervals were associated with longer duration of PD, more severe PD motor symptoms, a higher postural-instability-gait-disturbance (PIGD) score, and worse freezing of gait. Longer D-intervals were not associated with disease duration or PD motor symptoms. Neither the D- nor O-intervals were related to cognitive function. Individuals who employed the overlapping-strategy had more severe postural instability (i.e., higher PIGD scores), as compared to those who used the distinct-strategy. SIGNIFICANCE: In contrast to older adults without PD, most patients with PD utilize the overlapping strategy. Poorer postural and gait control are associated with the strategy choice and with the duration of concurrent performance of turning and sitting. Additional work is needed to further explicate the mechanisms underlying these strategies and their clinical implications.

SPARC: a new approach to quantifying gait smoothness in patients with Parkinson's disease.

BACKGROUND: Impairments in biomechanics and neural control can disrupt the timing and muscle pattern activation necessary for smooth gait. Gait is one of the most affected motor characteristics in Parkinson's disease (PD), but its smoothness has not been well-studied. This work applies the recently proposed spectral arc length measure (SPARC) to study, for the first time, gait in patients with PD. We hypothesized that the gait of patients with PD would be less smooth than that of healthy controls, as reflected in the SPARC measures. METHODS: The gait of 101 PD patients and 39 healthy controls was assessed using an inertial sensor. Smoothness of gait was estimated with SPARC (respectively from acceleration and angular velocity signals, SPARC-Acc and SPARC-Gyro) and harmonic ratios. Correlations between SPARC, traditional gait measures and the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Measurements and analysis were conducted with and without anti-PD medication. RESULTS: SPARC measures were lower (less smooth) in PD than in controls (SPARC-Acc: PD: - 6.11 ± 0.74; CO: -5.17 ± 0.79; p <  0.001). When comparing PD to controls, SPARC-Acc differed more than other measures of gait (i.e., largest effect size, which was > 1). SPARC measures were correlated with UPDRS motor score (r = - 0.65), while they were independent of other measures of gait smoothness. PD gait in the on state was smoother than in the off state (p <  0.001). CONCLUSIONS: SPARC calculated from trunk acceleration and angular velocity signals provide valid measures of walking smoothness in PD. SPARC is sensitive to Parkinson's disease and PD medications and can be used of as another, complementary measure of the motor control of walking in PD.

Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson's Disease.

In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

Turn Around Freezing: Community-Living Turning Behavior in People with Parkinson's Disease.

Difficulty in turning while walking is common among patients with Parkinson's disease (PD). This difficulty often leads to significant disability, falls, and loss of function; moreover, turning is a common trigger for freezing of gait (FoG). We hypothesized that the quantity and quality of turning mobility while walking during daily life would be different among subjects with PD with and without FoG. Here, we investigated, for the first time, the turning quality during daily life as it relates to FoG in people with PD using a single inertial sensor. Ninety-four subjects with PD (among whom 25 had FoG) wore an inertial sensor attached by a belt on the lower back during normal daily activity consecutively for 3 days. An algorithm identified periods of walking and calculated the number and quality metrics of turning. Quality, but not the quantity, of turning at home was different in freezers compared to the non-freezers. The number of turns (19.3 ± 9.2/30 min in freezers, 22.4 ± 12.9/30 min non-freezers; p = 0.194) was similar in the two groups. Some aspects of quality of turns, specifically mean jerkiness, mean and variability of medio-lateral jerkiness were significantly higher (p < 0.05) in the freezers, compared to non-freezers. Interestingly, subjects with FoG showed specific turning differences in the turns with larger angles compared to those without FoG. These findings suggest that turning during daily activities among patients with PD is impaired in subjects with FoG, compared to subject without freezing. As such, clinical decision-making and rehabilitation assessment may benefit from measuring the quality of turning mobility during daily activities in PD.

Who will remain tremor dominant? The possible role of cognitive reserve in the time course of two common Parkinson's disease motor subtypes.

In a prospective 5-year study among Parkinson's disease (PD) tremor-dominant (TD) patients, we investigated who will remain TD and who will later convert into the postural instability gait difficulty (PIGD) phenotype. At follow-up, 38% were still considered TD. At baseline the TD non-convertors had more years of education and better cognitive function than the convertors and significantly smaller deterioration in gait, balance, cognitive function and other non-motor symptoms. These results highlight the potential role of cognition in protecting against the development of PIGD symptoms.