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Abstract Parkinson’s disease (PD) can cause postural instability, which may result in falls. These issues have been associated with motor and non-motor symptoms (NMS), including cognitive dysfunction. Several techniques have been employed to investigate the underlying neural mechanisms involved in postural control in PD. These include behavioural studies assessing associations between cognition and postural control, functional neuroimaging studies, and resting-state neural correlates. This review provides an overview of these emerging bodies of research. Scopus, PubMed, and ProQuest were searched and detailed the brain-imaging technique, cohort, and postural control measures. A total of 79 studies were identified. Findings supported the notion of cortical involvement in postural control function to compensate for subcortical damage resulting from PD. Future studies should standardise their outcome measures and data analysis to allow comparisons of results across studies and ensure more comprehensive and robust data collection to enhance the reliability and validity of these findings.

Ocular microtremor (OMT) is a fixational eye movement that cannot be seen with the naked eye but is always present, even when the eye appears motionless/still. The link between OMT and brain function provides a strong rationale for investigation as there lies potential for its use as a biomarker in populations with neurological impairments. OMT frequency is typically 70-80Hz in healthy adults and research suggests that this will be reduced in those with neurological disease such as Parkinson's Disease (PD). This study aims to examine OMT in people with PD compared to healthy older adults. This is an exploratory, observational study that will use a novel handheld device-The iTremor ONE, which has been developed to rapidly, non-invasively assess and evaluate OMT frequency. This device uses incident laser technology directed at the sclera. People with PD who meet the inclusion criteria will participate in a home-based assessment involving cognitive, motor (using the UPDRS-III) and OMT measures. With OMT as the primary outcome, assessment with the iTremor is quick, taking just three seconds to obtain a reading. People with PD will be invited into the laboratory to perform extensive cognitive assessments along with an assessment of balance, gait, and turning using wearable sensors. People with PD will be assessed both off, and on, their anti-parkinsonian medication following a 12 hour washout period. We will recruit 30 People with PD, 30 people with suspected PD and 30 age-matched healthy control participants for assessment of OMT. 20 People with PD will complete a test-retest reliability assessment at the same approximate time, exactly one week after their initial visit under the same conditions to explore consistency. This will be the first study of its kind to non-invasively investigate OMT frequency as a marker/monitor for PD with advanced technology that could be used within the clinic, laboratory, or home. Identifying OMT as a PD biomarker could better support clinical assessment, enabling improved provision of care to patients with advanced disease monitoring. Clinical trial registration: This trial is registered at clinicaltrials.gov (NCT06051877; September 2023).

BackgroundThere is currently no pharmacological treatment for visuo-cognitive impairments in Parkinson's disease. Alternative strategies are needed to address these non-motor symptoms given their impact on quality of life. Novel technologies have potential to deliver multimodal rehabilitation of visuo-cognitive dysfunction, but more research is required to determine their feasibility in Parkinson's.ObjectiveTo determine the feasibility and preliminary efficacy of a home-based, technological visuo-cognitive training (TVT) intervention using a mobile application and exercise with stroboscopic glasses compared to non-technological care in people with Parkinson's.MethodsThis 18-month, parallel, two-arm pilot trial took place between July 2021-December 2022. Participants were community-dwelling individuals with a diagnosis of Parkinson's, aged over 50 years. Participants were randomly allocated to one of two active four-week interventions, TVT (n = 20) or standard care (SC) (n = 20). A physiotherapist delivered 8 home visits over 4 weeks, lasting 45-60 mins. Participants were evaluated at baseline and then on completion of the intervention. Primary outcomes were feasibility of the study design and intervention (recruitment/retention, adherence, assessment time scale, equipment and safety). Exploratory outcomes included assessments of cognitive, visual, clinical and motor function. (Blinding of participants was not possible due to the nature of the intervention).ResultsThe recruitment rate was 60% (40/67), and the retention rate was 98% (39/40). Adherence to both arms of the intervention was high, with participants attending 98% of visits in the TVT group and 96% of visits in the SC group. 35% (9/20) of participants in the TVT group experienced mild symptoms associated with use of the stroboscopic glasses which included dizziness, queasiness and unsteadiness. There were minimal between group differences, with both interventions having positive effects on a variety of clinical, cognitive, and physical performance outcomes.ConclusionsOur findings suggest that home-based TVT with a physiotherapist is feasible in people with Parkinson's and could provide an alternative approach to addressing cognitive and motor dysfunction in this population. We make recommendations for future trials and invite ensuing studies to improve upon the design and utilise stroboscopic visual training and digital tools to investigate this emerging area of multimodal rehabilitation. This trial was prospectively registered at ISRCTN (registration number: ISRCTN46164906; https://doi.org/10.1186/ISRCTN46164906).

Abstract Wearable inertial measurement units (IMUs) are being used to quantify gait characteristics that are associated with increased fall risk, but the current limitation is the lack of contextual information that would clarify IMU data. Use of wearable video-based cameras would provide a comprehensive understanding of an individual’s habitual fall risk, adding context to clarify abnormal IMU data. Generally, there is taboo when suggesting the use of wearable cameras to capture real-world video, clinical and patient apprehension due to ethical and privacy concerns. This perspective proposes that routine use of wearable cameras could be realized within digital medicine through AI-based computer vision models to obfuscate/blur/shade sensitive information while preserving helpful contextual information for a comprehensive patient assessment. Specifically, no person sees the raw video data to understand context, rather AI interprets the raw video data first to blur sensitive objects and uphold privacy. That may be more routinely achieved than one imagines as contemporary resources exist. Here, to showcase/display the potential an exemplar model is suggested via off-the-shelf methods to detect and blur sensitive objects (e.g., people) with an accuracy of 88%. Here, the benefit of the proposed approach includes a more comprehensive understanding of an individual’s free-living fall risk (from free-living IMU-based gait) without compromising privacy. More generally, the video and AI approach could be used beyond fall risk to better inform habitual experiences and challenges across a range of clinical cohorts. Medicine is becoming more receptive to wearables as a helpful toolbox, camera-based devices should be plausible instruments.

Eye-movement assessment is a key component of neurological evaluation, offering valuable insights into neural deficits and underlying mechanisms. This narrative review explores the emerging subject of digital eye-movement outcomes (DEMOs) and their potential as sensitive biomarkers for neurological impairment. Eye tracking has become a useful method for investigating visual system functioning, attentional processes, and cognitive mechanisms. Abnormalities in eye movements, such as altered saccadic patterns or impaired smooth pursuit, can act as important diagnostic indicators for various neurological conditions. The non-invasive nature, cost-effectiveness, and ease of implementation of modern eye-tracking systems makes it particularly attractive in both clinical and research settings. Advanced digital eye-tracking technologies and analytical methods enable precise quantification of eye-movement parameters, complementing subjective clinical evaluations with objective data. This review examines how DEMOs could contribute to the localisation and diagnosis of neural impairments, potentially serving as useful biomarkers. By comprehensively exploring the role of eye-movement assessment, this review aims to highlight the common eye-movement deficits seen in neurological injury and disease by using the examples of mild traumatic brain injury and Parkinson’s Disease. This review also aims to enhance the understanding of the potential use of DEMOs in diagnosis, monitoring, and management of neurological disorders, ultimately improving patient care and deepening our understanding of complex neurological processes. Furthermore, we consider the broader implications of this technology in unravelling the complexities of visual processing, attention mechanisms, and cognitive functions. This review summarises how DEMOs could reshape our understanding of brain health and allow for more targeted and effective neurological interventions.

Visual problems are common in people who have neurological injury or disease, with deficits linked to postural control and gait impairment. Vision therapy could be a useful intervention for visual impairment in various neurological conditions such as stroke, head injury, or Parkinson’s disease. Stroboscopic visual training (SVT) has been shown to improve aspects of visuomotor and cognitive performance in healthy populations, but approaches vary with respect to testing protocols, populations, and outcomes. The purpose of this structured review was to examine the use of strobe glasses as a training intervention to inform the development of robust protocols for use in clinical practice. Within this review, any studies using strobe glasses as a training intervention with visual or motor performance–related outcomes was considered. PubMed, Scopus, and ProQuest databases were searched in January 2023. Two independent reviewers (JD and RM) screened articles that used strobe glasses as a training tool. A total of 33 full text articles were screened, and 15 met inclusion/exclusion criteria. Reported outcomes of SVT included improvements in short–term memory, attention, and visual response times, with emerging evidence for training effects translating to balance and physical performance. However, the lack of standardisation across studies for SVT protocols, variation in intervention settings, duration and outcomes, and the limited evidence within clinical populations demonstrates that further work is required to determine optimal strobe dosage and delivery. This review highlights the potential benefits, and existing research gaps regarding the use of SVT in clinical practice, with recommendations for clinicians considering adopting this technology as part of future studies in this emerging field. Author summary Visual problems are common in people who have neurological disease and can affect balance and walking. Vision therapy could be a useful intervention for visual problems in various neurological conditions such as stroke, head injury, or Parkinson’s disease. Stroboscopic visual training (SVT) is a type of visual training that involves the use of specialist glasses equipped with liquid crystal technology lenses. These lenses regulate visual information by producing an intermittent clear and opaque flicker effect without light or flash being used. Training with these glasses has been shown to improve aspects of visuomotor and cognitive (thinking) performance in healthy populations, but approaches to training vary. Here, we examine the use of strobe glasses as a training intervention with the aim to help develop protocols for use in clinical practice. We found evidence that SVT can improve visual skills, with the potential to enhance aspects of physical performance such as balance. However, we also found a lack of standardisation across studies for SVT protocols, and there was limited evidence for use of SVT within clinical populations. Our review not only highlights the potential benefits of using SVT in clinical practice but also emphasises where there are gaps in the current research. Based on our finding, we have made recommendations to help guide future research in this emerging field.

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.

BackgroundMobile applications and technology (e.g., stroboscopic glasses) are increasingly being used to deliver combined visual and cognitive (termed visuo-cognitive) training that replaces standard pen and paper-based interventions. These 'technological visuo-cognitive training' (TVT) interventions could help address the complex problems associated with visuo-cognitive dysfunction in people with long term neurological conditions such as Parkinson's disease. As data emerges to support the effectiveness of these technologies, patient perspectives offer an insight into how novel TVT is received by people living with long term neurological conditions.ObjectiveTo explore experiences of people with Parkinson's in using technology as part of a home-based visuo-cognitive training programme compared to traditional approaches to rehabilitation.MethodsEight people with Parkinson's who took part in a pilot randomised cross-over trial, investigating the efficacy and feasibility of TVT compared to standard care, were interviewed to explore their experiences of each arm of the training they received. Integration of Normalisation Process Theory (NPT) into the analysis enabled examination of the potential to embed novel TVT into a home-based rehabilitation intervention for people with Parkinson's disease.ResultsThree key themes emerged from the thematic analysis as factors influencing the implementation potential of TVT for people with Parkinson's disease: perceived value of technology, perceived ease of use and support mechanisms. Further examination of the data through the lens of NPT revealed that the implantation and embedding of novel technology was dependent on positive user experience, individual disease manifestation and engagement with a professional.ConclusionsOur findings provide insights into the challenges of engaging with technology-based interventions while living with a progressive and fluctuating disease. When implementing technology-based interventions for people with Parkinson's, we recommend that patients and clinicians collaborate to determine whether the technology fits the capacity, preference, and treatment needs of the individual patient.

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.

BackgroundPhysical activity is encouraged for people with Multiple Sclerosis. Yoga is a popular form of physical activity and is chosen by some people with Multiple Sclerosis. However, little is known about the impact of yoga for this population, alongside what influences ongoing engagement.AimThe aim of this study is to qualitatively explore the impact of online home-based yoga on people with Multiple Sclerosis and to explore factors that influence engagement.MethodsA qualitative study using semi-structured interviews and focus groups with people with Multiple Sclerosis and a yoga teacher. Thematic analysis was used to analyse the data. Ethical Approval was gained from Northumbria University.FindingsThree overarching themes emerged from the analysis. 'Yoga as engagement in physical activity' captured the reasoning for participating in yoga and how this method of physical activity was an alternative to physical activity done prior to diagnosis. Frustration was apparent within this theme that some individuals were unable to engage in the range of physical activity that they wished to. 'Yoga is a personalised approach' demonstrated the flexibility and inclusivity of yoga, for individuals with varying symptoms to be able to engage with. Finally, 'yoga impacts individuals both physically and psychologically' captured the focus on the psychological impact of yoga, improving wellbeing and control.ConclusionsYoga gives people with Multiple Sclerosis the feeling of control over their symptoms and a means to engage with meaningful physical activity. Prior involvement in physical activity influenced engagement in yoga and wanting to push themselves. There was reluctance among this group to engage with aerobic activity, which warrants future investigation and support from health and exercise professionals.

Gait assessment is essential to understand injury prevention mechanisms during running, where high-impact forces can lead to a range of injuries in the lower extremities. Information regarding the running style to increase efficiency and/or selection of the correct running equipment, such as shoe type, can minimize the risk of injury, e.g., matching a runner's gait to a particular set of cushioning technologies found in modern shoes (neutral/support cushioning). Awareness of training or selection of the correct equipment requires an understanding of a runner's biomechanics, such as determining foot orientation when it strikes the ground. Previous work involved a low-cost approach with a foot-mounted inertial measurement unit (IMU) and an associated zero-crossing-based methodology to objectively understand a runner's biomechanics (in any setting) to learn about shoe selection. Here, an investigation of the previously presented ZC-based methodology is presented only to determine general validity for running gait assessment in a range of running abilities from novice (8 km/h) to experienced (16 km/h+). In comparison to Vicon 3D motion tracking data, the presented approach can extract pronation, foot strike location, and ground contact time with good [ICC(2,1) > 0.750] to excellent [ICC(2,1) > 0.900] agreement between 8–12 km/h runs. However, at higher speeds (14 km/h+), the ZC-based approach begins to deteriorate in performance, suggesting that other features and approaches may be more suitable for faster running and sprinting tasks.

Although the multifactorial nature of falls in Parkinson’s disease (PD) is well described, optimal assessment for the identification of fallers remains unclear. Thus, we aimed to identify clinical and objective gait measures that best discriminate fallers from non-fallers in PD, with suggestions of optimal cutoff scores. METHODS: Individuals with mild-to-moderate PD were classified as fallers (n = 31) or non-fallers (n = 96) based on the previous 12 months’ falls. Clinical measures (demographic, motor, cognitive and patient-reported outcomes) were assessed with standard scales/tests, and gait parameters were derived from wearable inertial sensors (Mobility Lab v2); participants walked overground, at a self-selected speed, for 2 min under single and dual-task walking conditions (maximum forward digit span). Receiver operating characteristic curve analysis identified measures (separately and in combination) that best discriminate fallers from non-fallers; we calculated the area under the curve (AUC) and identified optimal cutoff scores (i.e., point closest-to-(0,1) corner). RESULTS: Single gait and clinical measures that best classified fallers were foot strike angle (AUC = 0.728; cutoff = 14.07°) and the Falls Efficacy Scale International (FES-I; AUC = 0.716, cutoff = 25.5), respectively. Combinations of clinical + gait measures had higher AUCs than combinations of clinical-only or gait-only measures. The best performing combination included the FES-I score, New Freezing of Gait Questionnaire score, foot strike angle and trunk transverse range of motion (AUC = 0.85). CONCLUSION: Multiple clinical and gait aspects must be considered for the classification of fallers and non-fallers in PD.

BackgroundYoga has multiple benefits for individuals living with Multiple Sclerosis (MS), including reduced pain, depression, fatigue, strength, and improved quality of life. During the COVID-19 pandemic, home-based delivery of yoga increased. However, no studies to date have explored online home-based yoga for individuals living with MS, more specifically the motivations, experiences, or the sustainability of home-based yoga practice for individuals living with MS.AimThis study aimed to explore the facilitators and barriers of online yoga provision for individuals living with MS.MethodsOne focus group and three semi-structured interviews were carried out online via Zoom with one yoga instructor and seven yoga participants living with MS. Thematic Analysis was used to analyse this data.FindingsTwo themes were generated from the interviews, the environment and future provision, each with their own sub-themes. The themes reflect various facilitators and barriers of home-based yoga provision which differed depending upon the individuals home environment, social connections, physical ability, and confidence practising yoga. Furthermore, preferences of home provision fluctuated over time depending upon symptoms of MS.ConclusionsHome-based yoga practice is a viable and enjoyable option for individuals living with MS. It is recommended that yoga studios offering home-based yoga provision consider individual differences in preference, as well as fluctuations in symptoms that may create inequitable access to services and may prevent participation for some.

Visual and cognitive dysfunction are common in Parkinson's disease and relate to balance and gait impairment, as well as increased falls risk and reduced quality of life. Vision and cognition are interrelated (termed visuo-cognition) which makes intervention complex in people with Parkinson's (PwP). Non-pharmacological interventions for visuo-cognitive deficits are possible with modern technology, such as combined mobile applications and stroboscopic glasses, but evidence for their effectiveness in PwP is lacking. We aim to investigate whether technological visuo-cognitive training (TVT) can improve visuo-cognitive function in PwP. We will use a parallel group randomised controlled trial to evaluate the feasibility and acceptability of TVT versus standard care in PwP. Forty PwP who meet our inclusion criteria will be randomly assigned to one of two visuo-cognitive training interventions. Both interventions will be carried out by a qualified physiotherapist in participants own homes (1-hour sessions, twice a week, for 4 weeks). Outcome measures will be assessed on anti-parkinsonian medication at baseline and at the end of the 4-week intervention. Feasibility of the TVT intervention will be assessed in relation to safety and acceptability of the technological intervention, compliance and adherence to the intervention and usability of equipment in participants homes. Additionally, semi structured interviews will be conducted to explore participants' experience of the technology. Exploratory efficacy outcomes will include change in visual attention measured using the Trail Making Test as well as changes in balance, gait, quality of life, fear of falling and levels of activity. This pilot study will focus on the feasibility and acceptability of TVT in PwP and provide preliminary data to support the design of a larger, multi-centre randomised controlled trial. This trial is registered at isrctn.com (ISRCTN46164906).

Running gait assessment is essential for the development of technical optimization strategies as well as to inform injury prevention and rehabilitation. Currently, running gait assessment relies on (i) visual assessment, exhibiting subjectivity and limited reliability, or (ii) use of instrumented approaches, which often carry high costs and can be intrusive due to the attachment of equipment to the body. Here, the use of an IoT-enabled markerless computer vision smartphone application based upon Google’s pose estimation model BlazePose was evaluated for running gait assessment for use in low-resource settings. That human pose estimation architecture was used to extract contact time, swing time, step time, knee flexion angle, and foot strike location from a large cohort of runners. The gold-standard Vicon 3D motion capture system was used as a reference. The proposed approach performs robustly, demonstrating good (ICC(2,1) > 0.75) to excellent (ICC(2,1) > 0.90) agreement in all running gait outcomes. Additionally, temporal outcomes exhibit low mean error (0.01–0.014 s) in left foot outcomes. However, there are some discrepancies in right foot outcomes, due to occlusion. This study demonstrates that the proposed low-cost and markerless system provides accurate running gait assessment outcomes. The approach may help routine running gait assessment in low-resource environments.

Background: Turning is a complex measure of gait that accounts for over 50% of daily steps. Traditionally, turning has been measured in a research grade laboratory setting, however, there is demand for a low-cost and portable solution to measure turning using wearable technology. This study aimed to determine the suitability of a low-cost inertial sensor-based device (AX6, Axivity) to assess turning, by simultaneously capturing and comparing to a turn algorithm output from a previously validated reference inertial sensor-based device (Opal), in healthy young adults. Methodology: Thirty participants (aged 23.9 ± 4.89 years) completed the following turning protocol wearing the AX6 and reference device: a turn course, a two-minute walk (including 180° turns) and turning in place, alternating 360° turn right and left. Both devices were attached at the lumbar spine, one Opal via a belt, and the AX6 via double sided tape attached directly to the skin. Turning measures included number of turns, average turn duration, angle, velocity, and jerk. Results: Agreement between the outcomes from the AX6 and reference device was good to excellent for all turn characteristics (all ICCs > 0.850) during the turning 360° task. There was good agreement for all turn characteristics (all ICCs > 0.800) during the two-minute walk task, except for moderate agreement for turn angle (ICC 0.683). Agreement for turn outcomes was moderate to good during the turns course (ICCs range; 0.580 to 0.870). Conclusions: A low-cost wearable sensor, AX6, can be a suitable and fit-for-purpose device when used with validated algorithms for assessment of turning outcomes, particularly during continuous turning tasks. Future work needs to determine the suitability and validity of turning in aging and clinical cohorts within low-resource settings.

Turning is a common impairment of mobility in people with Parkinson’s disease (PD), which increases freezing of gait (FoG) episodes and has implications for falls risk. Visual cues have been shown to improve general gait characteristics in PD. However, the effects of visual cues on turning deficits in PD remains unclear. We aimed to (i) compare the response of turning performance while walking (180° and 360° turns) to visual cues in people with PD with and without FoG; and (ii) examine the relationship between FoG severity and response to visual cues during turning. This exploratory interventional study measured turning while walking in 43 participants with PD (22 with self-reported FoG) and 20 controls using an inertial sensor placed at the fifth lumbar vertebrae region. Participants walked straight and performed 180° and 360° turns midway through a 10 m walk, which was done with and without visual cues (starred pattern). The turn duration and velocity response to visual cues were assessed using linear mixed effects models. People with FoG turned slower and longer than people with PD without FoG and controls (group effect: p < 0.001). Visual cues reduced the velocity of turning 180° across all groups and reduced the velocity of turning 360° in people with PD without FoG and controls. FoG severity was not significantly associated with response to visual cues during turning. Findings suggest that visual cueing can modify turning during walking in PD, with response influenced by FoG status and turn amplitude. Slower turning in response to visual cueing may indicate a more cautious and/or attention-driven turning pattern. This study contributes to our understanding of the influence that cues can have on turning performance in PD, particularly in freezers, and will aid in their therapeutic application.

Background: Gait disturbance is an early, cardinal feature of Parkinson’s disease (PD) associated with falls and reduced physical activity. Progression of gait impairment in Parkinson’s disease is not well characterized and a better understanding is imperative to mitigate impairment. Subtle gait impairments progress in early disease despite optimal dopaminergic medication. Evaluating gait disturbances over longer periods, accounting for typical aging and dopaminergic medication changes, will enable a better understanding of gait changes and inform targeted therapies for early disease. This study aimed to describe gait progression over the first 6 years of PD by delineating changes associated with aging, medication, and pathology.Methods: One-hundred and nine newly diagnosed PD participants and 130 controls completed at least two gait assessments. Gait was assessed at 18-month intervals for up to 6 years using an instrumented walkway to measure sixteen spatiotemporal gait characteristics. Linear mixed-effects models assessed progression.Results: Ten gait characteristics significantly progressed in PD, with changes in four of these characteristics attributable to disease progression. Age-related changes also contributed to gait progression; changes in another two characteristics reflected both aging and disease progression. Gait impairment progressed irrespective of dopaminergic medication change for all characteristics except step width variability.Conclusions: Discrete gait impairments continue to progress in PD over 6 years, reflecting a combination of, and potential interaction between, disease-specific progression and age-related change. Gait changes were mostly unrelated to dopaminergic medication adjustments, highlighting limitations of current dopaminergic therapy and the need to improve interventions targeting gait decline.

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.

Participating in habitual physical activity (HPA) may slow onset of dependency and disability for people with Parkinson’s disease (PwP). While cognitive and physical determinants of HPA are well understood, psychosocial influences are not. This pilot study aimed to identify psychosocial factors associated with HPA to guide future intervention development. Sixty-four PwP participated in this study; forty had carer informants. PwP participants wore a tri-axial accelerometer on the lower back continuously for seven days at two timepoints (18 months apart), measuring volume, pattern and variability of HPA. Linear mixed effects analysis identified relationships between demographic, clinical and psychosocial data and HPA from baseline to 18 months. Key results in PwP with carers indicated that carer anxiety and depression were associated with increased HPA volume (p < 0.01), while poorer carer self-care was associated with reduced volume of HPA over 18 months (p < 0.01). Greater carer strain was associated with taking longer walking bouts after 18 months (p < 0.01). Greater carer depression was associated with lower variability of HPA cross-sectionally (p = 0.009). This pilot study provides preliminary novel evidence that psychosocial outcomes from PwP’s carers may impact HPA in Parkinson’s disease. Interventions to improve HPA could target both PwP and carers and consider approaches that also support psychosocial wellbeing.

Early features of Parkinson's disease (PD) include both motor and cognitive changes, suggesting shared common pathways. A common motor dysfunction is postural instability, a known predictor of falls, which have a major impact on quality of life. Understanding mechanisms of postural dynamics in PD and specifically how they relate to cognitive changes is essential for developing effective interventions. The aims of this study were to examine the changes that occur in postural metrics over time and explore the relationship between postural and cognitive dysfunction. The study group consisted of 35 people (66 ± 8years, 12 female, UPDRS III: 22.5 ± 9.6) diagnosed with PD who were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—PD Gait (ICICLE-GAIT) study. Postural and cognitive assessments were performed at 18, 36, and 54 months after enrolment. Participants stood still for 120 s, eyes open and arms by their side. Postural dynamics were measured using metrics derived from a single tri-axial accelerometer (Axivity AX3, York, UK) on the lower back. Accelerometry metrics included jerk (derivative of acceleration), root mean square, frequency, and ellipsis (acceleration area). Cognition was evaluated by neuropsychological tests including the Montreal Cognitive Assessment (MoCA) and digit span. There was a significant decrease in accelerometry parameters, greater in the anteroposterior direction, and a decline in cognitive function over time. Accelerometry metrics were positively correlated with lower cognitive function and increased geriatric depression score and negatively associated with a qualitative measure of balance confidence. In conclusion, people with PD showed reduced postural dynamics that may represent a postural safety strategy. Associations with cognitive function and depression, both symptoms that may pre-empt motor symptoms, suggest shared neural pathways. Further studies, involving neuroimaging, may determine how these postural parameters relate to underlying neural and clinical correlates.