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.

Parkinson's disease (PD) is the second most common neurodegenerative disease; gait impairments are typical and are associated with increased fall risk and poor quality of life. Gait is potentially a useful biomarker to help discriminate PD at an early stage, however the optimal characteristics and combination are unclear. In this study, we used machine learning (ML) techniques to determine the optimal combination of gait characteristics to discriminate people with PD and healthy controls (HC). 303 participants (119 PD, 184 HC) walked continuously around a circuit for 2-minutes at a self-paced walk. Gait was quantified using an instrumented mat (GAITRite) from which 16 gait characteristics were derived and assessed. Gait characteristics were selected using different ML approaches to determine the optimal method (random forest with information gain and recursive features elimination (RFE) technique with support vector machine (SVM) and logistic regression). Five clinical gait characteristics were identified with RFE-SVM (mean step velocity, mean step length, step length variability, mean step width, and step width variability) that accurately classified PD. Model accuracy for classification of early PD ranged between 73-97% with 63-100% sensitivity and 79-94% specificity. In conclusion, we identified a subset of gait characteristics for accurate early classification of PD. These findings pave the way for a better understanding of the utility of ML techniques to support informed clinical decision-making.

Parkinson's disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.

Participating in habitual physical activity (HPA) can support people with dementia and mild cognitive impairment (MCI) to maintain functional independence. Digital technology can continuously measure HPA objectively, capturing nuanced measures relating to its volume, intensity, pattern, and variability.

Sarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD concentrations are low in older people with sarcopenia, and increasing skeletal muscle NAD concentrations may offer a novel therapy for this condition. Acipimox is a licensed lipid-lowering agent known to act as an NAD precursor. This open-label, uncontrolled, before-and-after proof-of-concept experimental medicine study will test whether daily supplementation with acipimox improves skeletal muscle NAD concentrations.

The use of miniaturized magneto-inertial measurement units (MIMUs) allows for an objective evaluation of gait and a quantitative assessment of clinical outcomes. Spatial and temporal parameters are generally recognized as key metrics for characterizing gait. Although several methods for their estimate have been proposed, a thorough error analysis across different pathologies, multiple clinical centers and on large sample size is still missing. The aim of this study was to apply a previously presented method for the estimate of spatio-temporal parameters, named Trusted Events and Acceleration Direct and Reverse Integration along the direction of Progression (TEADRIP), on a large cohort (236 patients) including Parkinson, mildly cognitively impaired and healthy older adults collected in four clinical centers. Data were collected during straight-line gait, at normal and fast walking speed, by attaching two MIMUs just above the ankles. The parameters stride, step, stance and swing durations, as well as stride length and gait velocity, were estimated for each gait cycle. The TEADRIP performance was validated against data from an instrumented mat.

Measurement of real-world physical activity (PA) data using accelerometry in older adults is informative and clinically relevant, but not without challenges. This review appraises the reliability and validity of accelerometry-based PA measures of older adults collected in real-world conditions. Eight electronic databases were systematically searched, with 13 manuscripts included. Intraclass correlation coefficient (ICC) for inter-rater reliability were: walking duration (0.94 to 0.95), lying duration (0.98 to 0.99), sitting duration (0.78 to 0.99) and standing duration (0.98 to 0.99). ICCs for relative reliability ranged from 0.24 to 0.82 for step counts and 0.48 to 0.86 for active calories. Absolute reliability ranged from 5864 to 10,832 steps and for active calories from 289 to 597 kcal. ICCs for responsiveness for step count were 0.02 to 0.41, and for active calories 0.07 to 0.93. Criterion validity for step count ranged from 0.83 to 0.98. Percentage of agreement for walking ranged from 63.6% to 94.5%; for lying 35.6% to 100%, sitting 79.2% to 100%, and standing 38.6% to 96.1%. Construct validity between step count and criteria for moderate-to-vigorous PA was rs = 0.68 and 0.72. Inter-rater reliability and criterion validity for walking, lying, sitting and standing duration are established. Criterion validity of step count is also established. Clinicians and researchers may use these measures with a limited degree of confidence. Further work is required to establish these properties and to extend the repertoire of PA measures beyond "volume" counts to include more nuanced outcomes such as intensity of movement and duration of postural transitions.

Parkinson's disease (PD) is a common neurodegenerative disorder resulting in a range of mobility deficits affecting gait, balance and turning. In this paper, we present: (i) the development and validation of an algorithm to detect turns during gait; (ii) a method to extract turn characteristics; and (iii) the classification of PD using turn characteristics. Thirty-seven people with PD and 56 controls performed 180-degree turns during an intermittent walking task. Inertial measurement units were attached to the head, neck, lower back and ankles. A turning detection algorithm was developed and validated by two raters using video data. Spatiotemporal and signal-based characteristics were extracted and used for PD classification. There was excellent absolute agreement between the rater and the algorithm for identifying turn start and end (ICC ≥ 0.99). Classification modeling (partial least square discriminant analysis (PLS-DA)) gave the best accuracy of 97.85% when trained on upper body and ankle data. Balanced sensitivity (97%) and specificity (96.43%) were achieved using turning characteristics from the neck, lower back and ankles. Turning characteristics, in particular angular velocity, duration, number of steps, jerk and root mean square distinguished mild-moderate PD from controls accurately and warrant future examination as a marker of mobility impairment and fall risk in PD.

Ankylosing spondylitis is a major chronic rheumatic disease that predominantly affects axial joints, determining a rigid spine from the occiput to the sacrum. The dorsal hyperkyphosis may induce the patients to stand in a stooped position with consequent restriction in patients' daily living activities. The aim of this study was to develop a method for quantitatively and objectively assessing both balance and posture and their mutual relationship in ankylosing spondylitis subjects.

Quantification of gait with wearable technology is promising; recent cross-sectional studies showed that gait characteristics are potential prodromal markers for Parkinson disease (PD). The aim of this longitudinal prospective observational study was to establish gait impairments and trajectories in the prodromal phase of PD, identifying which gait characteristics are potentially early diagnostic markers of PD.

Falls are two to four times more frequent amongst older adults living in long-term care (LTC) than community-dwelling older adults and have deleterious consequences. It is hypothesised that a progressive exercise program targeting balance and strength will reduce fall rates when compared to a seated exercise program and do so cost effectively.

Parkinson's disease (PD) is a common age-related neurodegenerative disease. Gait impairment is frequent in the later stages of PD contributing to reduced mobility and quality of life. Digital biomarkers such as gait velocity and step length are predictors of motor and cognitive decline in PD. Additional gait parameters may describe different aspects of gait and motor control in PD. Sample entropy (SampEnt), a measure of signal predictability, is a nonlinear approach that quantifies regularity of a signal. This study investigated SampEnt as a potential biomarker for PD and disease duration. Real-world gait data over a seven-day period were collected using an accelerometer (Axivity AX3, York, UK) placed on the low back and gait metrics extracted. SampEnt was determined for the stride time, with vector length and threshold parameters optimized. People with PD had higher stride time SampEnt compared to older adults, indicating reduced gait regularity. The range of SampEnt increased over 36 months for the PD group, although the mean value did not change. SampEnt was associated with dopaminergic medication dose but not with clinical motor scores. In conclusion, this pilot study indicates that SampEnt from real-world data may be a useful parameter reflecting clinical status although further research is needed involving larger populations.

Early diagnosis of Parkinson's diseases (PD) is challenging; applying machine learning (ML) models to gait characteristics may support the classification process. Comparing performance of ML models used in various studies can be problematic due to different walking protocols and gait assessment systems. The objective of this study was to compare the impact of walking protocols and gait assessment systems on the performance of a support vector machine (SVM) and random forest (RF) for classification of PD. 93 PD and 103 controls performed two walking protocols at their normal pace: (i) four times along a 10 m walkway (intermittent walk-IW), (ii) walking for 2 minutes on a 25 m oval circuit (continuous walk-CW). 14 gait characteristics were extracted from two different systems (an instrumented walkway-GAITRite; and an accelerometer attached at the lower back-Axivity). SVM and RF were trained on normalized data (accounting for step velocity, gender, age and BMI) and evaluated using 10-fold cross validation with area under the curve (AUC). Overall performance was higher for both systems during CW compared to IW. SVM performed better than RF. With SVM, during CW Axivity significantly outperformed GAITRite (AUC: 87.83 ± 7.81% vs. 80.49 ± 9.85%); during IW systems performed similarly. These findings suggest that choice of testing protocol and sensing system may have a direct impact on ML PD classification results and highlight the need for standardization for wide scale implementation.

Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates.

Walking activity and gait parameters are considered among the most relevant mobility-related parameters. Currently, gait assessments have been mainly analyzed in laboratory or hospital settings, which only partially reflect usual performance (i.e., real world behavior). In this study, we aim to validate a robust walking detection algorithm using a single foot-worn inertial measurement unit (IMU) in real-life settings. We used a challenging dataset including 18 individuals performing free-living activities. A multi-sensor wearable system including pressure insoles, multiple IMUs, and infrared distance sensors (INDIP) was used as reference. Accurate walking detection was obtained, with sensitivity and specificity of 98 and 91% respectively. As robust walking detection is needed for ambulatory monitoring to complete the processing pipeline from raw recorded data to walking/mobility outcomes, a validated algorithm would pave the way for assessing patient performance and gait quality in real-world conditions.

The ability to walk independently is a primary goal for rehabilitation after stroke. Gait analysis provides a great amount of valuable information, while functional magnetic resonance imaging (fMRI) offers a powerful approach to define networks involved in motor control. The present study reports a new methodology based on both fMRI and gait analysis outcomes in order to investigate the ability of fMRI to reflect the phases of motor learning before/after electromyographic biofeedback treatment: the preliminary fMRI results of a post stroke subject's brain activation, during passive and active ankle dorsal/plantarflexion, before and after biofeedback (BFB) rehabilitation are reported and their correlation with gait analysis data investigated.

Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME).

Asymmetry is a cardinal symptom of gait post-stroke that is targeted during rehabilitation. Technological developments have allowed accelerometers to be a feasible tool to provide digital gait variables. Many acceleration-derived variables are proposed to measure gait asymmetry. Despite a need for accurate calculation, no consensus exists for what is the most valid and reliable variable. Using an instrumented walkway (GaitRite) as the reference standard, this study compared the validity and reliability of multiple acceleration-derived asymmetry variables. Twenty-five post-stroke participants performed repeated walks over GaitRite whilst wearing a tri-axial accelerometer (Axivity AX3) on their lower back, on two occasions, one week apart. Harmonic ratio, autocorrelation, gait symmetry index, phase plots, acceleration, and jerk root mean square were calculated from the acceleration signals. Test-retest reliability was calculated, and concurrent validity was estimated by comparison with GaitRite. The strongest concurrent validity was obtained from step regularity from the vertical signal, which also recorded excellent test-retest reliability (Spearman's rank correlation coefficients (rho) = 0.87 and Intraclass correlation coefficient (ICC21) = 0.98, respectively). Future research should test the responsiveness of this and other step asymmetry variables to quantify change during recovery and the effect of rehabilitative interventions for consideration as digital biomarkers to quantify gait asymmetry.

Accurate and reliable measurement of real-world walking activity is clinically relevant, particularly for people with mobility difficulties. Insights on walking can help understand mobility function, disease progression, and fall risks. People living in long-term residential care environments have heterogeneous and often pathological walking patterns, making it difficult for conventional algorithms paired with wearable sensors to detect their walking activity. We designed two walking bout detection algorithms for people living in long-term residential care. Both algorithms used thresholds on the magnitude of acceleration from a 3-axis accelerometer on the lower back to classify data as "walking" or "non-walking". One algorithm had generic thresholds, whereas the other used personalized thresholds. To validate and evaluate the algorithms, we compared the classifications of walking/non-walking from our algorithms to the real-time research assistant annotated labels and the classification output from an algorithm validated on a healthy population. Both the generic and personalized algorithms had acceptable accuracy (0.83 and 0.82, respectively). The personalized algorithm showed the highest specificity (0.84) of all tested algorithms, meaning it was the best suited to determine input data for gait characteristic extraction. The developed algorithms were almost 60% quicker than the previously developed algorithms, suggesting they are adaptable for real-time processing.