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Abstract Parkinson’s Disease is a progressive neurodegenerative disorder afflicting almost 12 million people. Increased understanding of its complex and heterogenous disease pathology, etiology and symptom manifestations has resulted in the need to design, capture and interrogate substantial clinical datasets. Herein we advocate how advances in the deployment of artificial intelligence models for Federated Data Analysis and Federated Learning can help spearhead coordinated and sustainable approaches to address this grand challenge.

Abstract The extent to which the heterogeneity of gait and balance problems in PD may be explained by genetic variation is unknown. Variants in the glucocerebrosidase (GBA) gene are the strongest known genetic risk factor for PD and are associated with greater motor and cognitive severity. However, the impact of GBA variants on comprehensive measures of gait and balance and their relationship to cognition remains unknown. We aimed to determine differences in gait and balance impairments in those with and without GBA variants (mutation carriers and E326K polymorphism) and explore direct and indirect effects of GBA status on gait, balance, and cognition. 332 participants, 43 of whom had GBA variants, were recruited. Participants completed a comprehensive, objective assessment of gait and standing balance using body-worn inertial sensors. Group differences in gait and balance between PD with and without GBA variants were assessed with linear regression, adjusting for age, gender, clinical testing site, disease duration, and apolipoprotein E (APOE) ɛ4 status. Structural equation modeling (SEM) explored direct relationships between GBA status and gait and balance and indirect relationships between GBA status and gait and balance via cognition. The GBA variant group had more impaired gait (pace and variability) and balance (sway area/jerk and sway velocity), than the non-GBA variant group. SEM demonstrated cognition as a mediator of GBA status on gait and balance. The close relationships among GBA, gait/balance, and cognition suggest potential for novel therapeutics to target the GBA pathway and/or cognition to improve mobility in PD GBA variants.

Background: Gait and balance impairments are among the most troublesome and heterogeneous in Parkinson’s disease (PD). This heterogeneity may, in part, reflect genetic variation. The apolipoprotein E (APOE) gene has three major allelic variants (ε2, ε3 and ε4). Previous work has demonstrated that older adult (OA) APOE ε4 carriers demonstrate gait deficits. This study compared gait and balance measures between APOE ε4 carriers and non-carriers in both OA and PD. Methods: 334 people with PD (81 APOE ε4 carriers and 253 non-carriers) and 144 OA (41 carriers and 103 non-carriers) were recruited. Gait and balance were assessed using body-worn inertial sensors. Two-way analyses of covariance (ANCOVA) compared gait and balance characteristics between APOE ε4 carriers and non-carriers in people with PD and OA, controlling for age, gender, and testing site. Results: Gait and balance were worse in people with PD compared to OA. However, there were no differences between APOE ε4 carriers and non-carriers in either the OA or PD group. In addition, there were no significant group (OA/PD) by APOE ε4 status (carrier/non-carrier) interaction effects for any measures of gait or balance. Conclusions: Although we found expected impairments in gait and balance in PD compared to OA, gait and balance characteristics did not differ between APOE ε4 carriers and non-carriers in either group. While APOE status did not impact gait and balance in this cross-sectional study, future work is needed to determine whether progression of gait and balance deficits is faster in PD APOE Ɛ4 carriers.

BackgroundWearable sensors could be a simple way to quantify and characterize mobility in patients with hematologic cancer scheduled to receive autologous hematopoietic stem cell transplant (autoHSCT) and how they may be related to common treatment-related symptoms and side effects of induction chemotherapy. ObjectiveWe aimed to conduct a cross-sectional study comparing mobility in patients scheduled to receive autoHSCT with that in healthy, age-matched adult controls and determine the relationships between patient mobility and chemotherapy-related symptoms. MethodsPatients scheduled to receive autoHSCT (78/156, 50%) and controls (78/156, 50%) completed the prescribed performance tests using wearable inertial sensors to quantify mobility including turning (turn duration and number of steps), gait (gait speed, stride time, stride time variability, double support time, coronal trunk range of motion, heel strike angle, and distance traveled), and balance (coronal sway, coronal range, coronal velocity, coronal centroidal frequency, sagittal sway, sagittal range, sagittal velocity, and sagittal centroidal frequency). Patients completed the validated patient-reported questionnaires to assess symptoms common to chemotherapy: chemotherapy-induced peripheral neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity subscale), nausea and pain (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), fatigue (Patient-Reported Outcomes Measurement Information System Fatigue Short Form 8a), vertigo (Vertigo Symptom Scale–short form), and depression (Center for Epidemiological Studies–Depression). Paired, 2-sided t tests were used to compare mobility between patients and controls. Stepwise multivariable linear regression models were used to evaluate associations between patient mobility and symptoms. ResultsPatients aged 60.3 (SD 10.3) years had significantly worse turning (turn duration; P

Abstract Background Many prostate cancer survivors are treated with androgen deprivation therapy (ADT), but these therapies may increase frailty, worsen physical functioning, and increase fall risk. While exercise may counter functional declines associated with ADT, no studies have tested whether and which type of exercise may reduce falls and frailty. The purpose of this trial is to compare the relative efficacy of strength training versus tai ji quan training against each other and to a stretching control group on falls, frailty, and physical functioning in men expose to ADT for prostate cancer. Methods Prostate cancer survivors treated with ADT (N = 360) who have fallen in the past year or are at risk of a fall based on validated risk factors will be recruited to participate in this single-blind, parallel group, randomized trial. Participants will be randomized to one of three supervised, group training programs: (i) strength training, (ii) tai ji quan training, or (iii) stretching (control), that train 3×/week for 6 months. Outcomes are assessed at baseline, 3 (mid-intervention), 6 (immediately post-intervention), and 12 (follow-up) months. The primary outcome is falls assessed by monthly self-report. Secondary outcomes include the following: frailty (low lean body mass (by bioelectrical impedance analysis), exhaustion (by SF-36 vitality scale), low activity (by CHAMPS physical activity survey), slowness (by 4 m usual walk speed), and weakness (by chair stand time)); objective and subjective measures of physical function will also be collected. Negative binomial regression models will be used to assess differences in falls between groups, while mixed effects modeling will be used to compare the relative efficacy of training group on secondary outcomes. Discussion Exercise represents a non-pharmacologic approach to mitigate the problem of falls experienced among men treated with ADT. By engaging in appropriate exercise, men may be able to avoid or delay falls, frailty, and disability associated with their cancer treatment. Findings of the trial are expected to inform clinical practice about how exercise could be prescribed as part of cancer care for prostate cancer survivors prescribed ADT. Trial registration ClinicalTrials.gov NCT03741335 . Registered on November 18, 2018.

Background: Mobility and sensorimotor inhibition impairments are heterogeneous in Parkinson's disease (PD). Genetics may contribute to this heterogeneity since the apolipoprotein (APOE) ε4 allele and glucocerebrosidase (GBA) gene variants have been related to mobility impairments in otherwise healthy older adult (OA) and PD cohorts. The purpose of this study is to determine if APOE or GBA genetic status affects sensorimotor inhibition and whether the relationship between sensorimotor inhibition and mobility differs in genetic sub-groups of PD.Methods: Ninety-three participants with idiopathic PD (53 non-carriers; 23 ε4 carriers; 17 GBA variants) and 72 OA (45 non-carriers; 27 ε4 carriers) had sensorimotor inhibition characterized by short-latency afferent inhibition. Mobility was assessed in four gait domains (pace/turning, rhythm, trunk, variability) and two postural sway domains (area/jerkiness and velocity) using inertial sensors.Results: Sensorimotor inhibition was worse in the PD than OA group, with no effect of genetic status. Gait pace/turning was slower and variability was higher (p < 0.01) in PD compared to OA. Postural sway area/jerkiness (p < 0.01) and velocity (p < 0.01) were also worse in the PD than OA group. Genetic status was not significantly related to any gait or postural sway domain. Sensorimotor inhibition was significantly correlated with gait variability (r = 0.27; p = 0.02) and trunk movement (r = 0.23; p = 0.045) in the PD group. In PD non-carriers, sensorimotor inhibition related to variability (r = 0.35; p = 0.010) and trunk movement (r = 0.31; p = 0.025). In the PD ε4 group, sensorimotor inhibition only related to rhythm (r = 0.47; p = 0.024), while sensorimotor inhibition related to pace/turning (r = −0.49; p = 0.046) and rhythm (r = 0.59; p = 0.013) in the PD GBA group. Sensorimotor inhibition was significantly correlated with gait pace/turning (r = −0.27; p = 0.04) in the OA group. There was no relationship between sensorimotor inhibition and postural sway.Conclusion: ε4 and GBA genetic status did not affect sensorimotor inhibition or mobility impairments in this PD cohort. However, worse sensorimotor inhibition was associated with gait variability in PD non-carriers, but with gait rhythm in PD ε4 carriers and with gait rhythm and pace in PD with GBA variants. Impaired sensorimotor inhibition had a larger effect on mobility in people with PD than OA and affected different domains of mobility depending on genetic status.

Introduction: This study aims at investigating whether impaired anticipatory postural adjustments (APA) during gait initiation contribute to the occurrence of freezing of gait (FOG) or whether altered APAs compensate for FOG in Parkinson’s disease (PD).Methods: Gait initiation after 30 s quiet stance was analyzed without and with a cognitive dual task (DT) in 33 PD subjects with FOG (PD+FOG), 30 PD subjects without FOG (PD-FOG), and 32 healthy controls (HC). APAs were characterized with inertial sensors and muscle activity of the tensor fasciae latae (TFL), gastrocnemius, and tibialis anterior was captured with electromyography recordings. Nine trials (of 190) were associated with start hesitation/FOG and analyzed separately.Results: PD+FOG and PD-FOG did not differ in disease duration, disease severity, age, or gender. PD+FOG had significantly smaller medio-lateral (ML) and anterio-posterior APAs compared to PD-FOG (DT, p < 0.05). PD+FOG had more co-contraction of left and right TFL during APAs compared to PD-FOG (p < 0.01). Within the PD+FOG, the ML size of APA (DT) was positively correlated with the severity of FOG history (NFOG-Q), with larger APAs associated with worse FOG (rho = 0.477, p = 0.025). ML APAs were larger during trials with observed FOG compared to trials of PD+FOG without FOG.Conclusions: People with PD who have a history of FOG have smaller ML APAs (weight shifting) during gait initiation compared to PD-FOG and HC. However, start hesitation (FOG) is not caused by an inability to sufficiently displace the center of mass toward the stance leg because APAs were larger during trials with observed FOG. We speculate that reducing the acceleration of the body center of mass with hip abductor co-contraction for APAs might be a compensatory strategy in PD+FOG, to address postural control deficits and enable step initiation.

Difficulty with turning is a major contributor to mobility disability and falls in people with movement disorders, such as Parkinson’s disease (PD). Turning often results in freezing and/or falling in patients with PD. However, asking a patient to execute a turn in the clinic often does not reveal their impairments. Continuous monitoring of turning with wearable sensors during spontaneous daily activities may help clinicians and patients determine who is at risk of falls and could benefit from preventative interventions. In this study, we show that continuous monitoring of natural turning with wearable sensors during daily activities inside and outside the home is feasible for people with PD and elderly people. We developed an algorithm to detect and characterize turns during gait, using wearable inertial sensors. First, we validate the turning algorithm in the laboratory against a Motion Analysis system and against a video analysis of 21 PD patients and 19 control (CT) subjects wearing an inertial sensor on the pelvis. Compared to Motion Analysis and video, the algorithm maintained a sensitivity of 0.90 and 0.76 and a specificity of 0.75 and 0.65, respectively. Second, we apply the turning algorithm to data collected in the home from 12 PD and 18 CT subjects. The algorithm successfully detects turn characteristics, and the results show that, compared to controls, PD subjects tend to take shorter turns with smaller turn angles and more steps. Furthermore, PD subjects show more variability in all turn metrics throughout the day and the week.

Purpose Chemotherapy-induced peripheral neuropathy (CIPN) may persist after treatment ends and may lead to functional decline and falls. This study compared objective and self-report measures of physical function, gait patterns, and falls between women cancer survivors with and without symptoms of CIPN to identify targets for functional rehabilitation. Methods A secondary data analysis of 512 women cancer survivors (age, 62 ± 6 years; time since diagnosis, 5.8 ± 4.1 years) categorized and compared women self-reporting symptoms of CIPN (CIPN+) with asymptomatic women (CIPN-) on the following: maximal leg strength, timed chair stand, physical function battery, gait characteristics (speed; step number, rate, and length; base of support), self-report physical function and disability, and falls in the past year. Results After an average of 6 years after treatment, 47% of women still reported symptoms of CIPN. CIPN+ had significantly worse self-report and objectively measured function than did CIPN-, with the exception of maximal leg strength and base of support during a usual walk. Gait was slower among CIPN+, with those women taking significantly more, but slower and shorter, steps than did CIPN- (all P < .05). CIPN+ reported significantly more disability and 1.8 times the risk of falls compared with CIPN- ( P < .0001). Increasing symptom severity was linearly associated with worsening function, increasing disability, and higher fall risk (all P < .05). Conclusion This work makes a significant contribution toward understanding the functional impact of CIPN symptoms on cancer survivors. Remarkably, 47% of women in our sample had CIPN symptoms many years after treatment, together with worse function, greater disability, and more falls. CIPN must be assessed earlier in the clinical pathway, and strategies to limit symptom progression and to improve function must be included in clinical and survivorship care plans.