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Results of a new study have shown the enormous potential of smartphone-collected, real-world data for the differentiation of patients with Parkinson disease from controls. This study spearheads a new phase for the evaluation of symptoms associated with Parkinson disease that is patient-centred, digital, objective, continuous and relevant to everyday life.

Many algorithms use 3D accelerometer and/or gyroscope data from inertial measurement unit (IMU) sensors to detect gait events (i.e., initial and final foot contact). However, these algorithms often require knowledge about sensor orientation and use empirically derived thresholds. As alignment cannot always be controlled for in ambulatory assessments, methods are needed that require little knowledge on sensor location and orientation, e.g., a convolutional neural network-based deep learning model. Therefore, 157 participants from healthy and neurologically diseased cohorts walked 5 m distances at slow, preferred, and fast walking speed, while data were collected from IMUs on the left and right ankle and shank. Gait events were detected and stride parameters were extracted using a deep learning model and an optoelectronic motion capture (OMC) system for reference. The deep learning model consisted of convolutional layers using dilated convolutions, followed by two independent fully connected layers to predict whether a time step corresponded to the event of initial contact (IC) or final contact (FC), respectively. Results showed a high detection rate for both initial and final contacts across sensor locations (recall ≥92%, precision ≥97%). Time agreement was excellent as witnessed from the median time error (0.005 s) and corresponding inter-quartile range (0.020 s). The extracted stride-specific parameters were in good agreement with parameters derived from the OMC system (maximum mean difference 0.003 s and corresponding maximum limits of agreement (−0.049 s, 0.051 s) for a 95% confidence level). Thus, the deep learning approach was considered a valid approach for detecting gait events and extracting stride-specific parameters with little knowledge on exact IMU location and orientation in conditions with and without walking pathologies due to neurological diseases.

Neuromodulatory or even neuroprotective therapy could soon be available for Parkinson's disease (PD), raising the question of how we should define and measure disease progression. Reported evidence suggests that several symptoms worsen with disease duration. Bradykinesia, rigidity, and activities of daily living deteriorate faster at the beginning of the disease, and this deterioration is paralleled by a decline in functional presynaptic dopaminergic activity, as shown by imaging techniques. Cognitive, speech, sleep, and gait difficulties might progress linearly in proportion to disease duration. Reduced variability in heart rate, orthostatic dysfunction, and visual hallucinations start to develop at mid-stage disease and are more common in late stages than earlier stages. In this Review, we summarise our current understanding of the progression of PD-associated symptoms and markers and conclude that an effective measurement of progression of PD must adapt to the different stages of the disease. In addition to routine clinical rating scales, new quantitative assessments of motor and non-motor symptoms, which should be more broadly available, reasonably priced, and easy-to-use, are needed.

Prevalence of gait impairments increases with age and is associated with mobility decline, fall risk and loss of independence. For geriatric patients, the risk of having gait disorders is even higher. Consequently, gait assessment in the clinics has become increasingly important. The purpose of the present study was to classify healthy young-middle aged, older adults and geriatric patients based on dynamic gait outcomes. Classification performance of three supervised machine learning methods was compared. From trunk 3D-accelerations of 239 subjects obtained during walking, 23 dynamic gait outcomes were calculated. Kernel Principal Component Analysis (KPCA) was applied for dimensionality reduction of the data for Support Vector Machine (SVM) classification. Random Forest (RF) and Artificial Neural Network (ANN) were applied to the 23 gait outcomes without prior data reduction. Classification accuracy of SVM was 89%, RF accuracy was 73%, and ANN accuracy was 90%. Gait outcomes that significantly contributed to classification included: Root Mean Square (Anterior-Posterior, Vertical), Cross Entropy (Medio-Lateral, Vertical), Lyapunov Exponent (Vertical), step regularity (Vertical) and gait speed. ANN is preferable due to the automated data reduction and significant gait outcome identification. For clinicians, these gait outcomes could be used for diagnosing subjects with mobility disabilities, fall risk and to monitor interventions.

Background Identification of individual gait events is essential for clinical gait analysis, because it can be used for diagnostic purposes or tracking disease progression in neurological diseases such as Parkinson’s disease. Previous research has shown that gait events can be detected from a shank-mounted inertial measurement unit (IMU), however detection performance was often evaluated only from straight-line walking. For use in daily life, the detection performance needs to be evaluated in curved walking and turning as well as in single-task and dual-task conditions. Methods Participants (older adults, people with Parkinson’s disease, or people who had suffered from a stroke) performed three different walking trials: (1) straight-line walking, (2) slalom walking, (3) Stroop-and-walk trial. An optical motion capture system was used a reference system. Markers were attached to the heel and toe regions of the shoe, and participants wore IMUs on the lateral sides of both shanks. The angular velocity of the shank IMUs was used to detect instances of initial foot contact (IC) and final foot contact (FC), which were compared to reference values obtained from the marker trajectories. Results The detection method showed high recall, precision and F1 scores in different populations for both initial contacts and final contacts during straight-line walking (IC: recall = 100%, precision = 100%, F1 score = 100%; FC: recall = 100%, precision = 100%, F1 score = 100%), slalom walking (IC: recall = 100%, precision ≥ 99%, F1 score = 100%; FC: recall = 100%, precision ≥ 99%, F1 score = 100%), and turning (IC: recall ≥ 85%, precision ≥ 95%, F1 score ≥ 91%; FC: recall ≥ 84%, precision ≥ 95%, F1 score ≥ 89%). Conclusions Shank-mounted IMUs can be used to detect gait events during straight-line walking, slalom walking and turning. However, more false events were observed during turning and more events were missed during turning. For use in daily life we recommend identifying turning before extracting temporal gait parameters from identified gait events.

Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers. Aging is a key risk factor for chronic diseases of the elderly. Here the authors perform large-scale miRNA profiling of blood from individuals of a range of ages and show that common diseases alter the physiological age-related blood microRNA profile.

Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them.

Step width is an important clinical motor marker for gait stability assessment. While laboratory-based systems can measure it with high accuracy, wearable solutions based on inertial measurement units do not directly provide spatial information such as distances. Therefore, we propose a magnetic estimation approach based on a pair of shank-worn magnetoelectric (ME) sensors. In this pilot study, we estimated the step width of eight healthy participants during treadmill walking and compared it to an optical motion capture (OMC) reference. In a direct comparison with OMC markers attached to the magnetic system, we achieved a high estimation accuracy in terms of the mean absolute error (MAE) for step width (≤1 cm) and step width variability (<0.1 cm). In a more general comparison with heel-mounted markers during the swing phase, the standard deviation of the error (<0.5 cm, measure for precision), the step width variability estimation MAE (<0.2 cm) and the Spearman correlation (>0.88) of individual feet were still encouraging, but the accuracy was negatively affected by a constant proxy bias (3.7 and 4.6 cm) due to the different anatomical reference points used in each method. The high accuracy of the system in the first case and the high precision in the second case underline the potential of magnetic motion tracking for gait stability assessment in wearable movement analysis.

Background Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages (“Braak stages”). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood. In this study we investigated the question of Tau spreading via small extracellular vesicles called exosomes. Methods Exosomes from different sources were analyzed by biochemical methods and electron microscopy (EM) and cryo-EM. Microfluidic devices that allow the culture of cell populations in different compartments were used to investigate the spreading of Tau. Results We show that Tau protein is released by cultured primary neurons or by N2a cells overexpressing different Tau constructs via exosomes. Neuron-derived exosomal Tau is hypo-phosphorylated, compared with cytosolic Tau. Depolarization of neurons promotes release of Tau-containing exosomes, highlighting the importance of neuronal activity. Using microfluidic devices we show that exosomes mediate trans-neuronal transfer of Tau depending on synaptic connectivity. Tau spreading is achieved by direct transmission of exosomes between neurons. In organotypic hippocampal slices, Tau-containing exosomes in conditioned medium are taken up by neurons and microglia, not astrocytes. In N2a cells, Tau assemblies are released via exosomes. They can induce inclusions of other Tau molecules in N2a cells expressing mutant human Tau. We also studied exosomes from cerebrospinal fluid in AD and control subjects containing monomeric and oligomeric Tau. Split-luciferase complementation reveals that exosomes from CSF can promote Tau aggregation in cultured cells. Conclusion Our study demonstrates that exosomes contribute to trans-synaptic Tau transmission, and thus offer new approches to control the spreading of pathology in AD and other tauopathies.

Gait speed often referred as the sixth vital sign is the most powerful biomarker of mobility. While a clinical setting allows the estimation of gait speed under controlled conditions that present functional capacity, gait speed in real-life conditions provides the actual performance of the patient. The goal of this study was to investigate objectively under what conditions during daily activities, patients perform as well as or better than in the clinic. To this end, we recruited 27 Parkinson’s disease (PD) patients and measured their gait speed by inertial measurement units through several walking tests in the clinic as well as their daily activities at home. By fitting a bimodal Gaussian model to their gait speed distribution, we found that on average, patients had similar modes in the clinic and during daily activities. Furthermore, we observed that the number of medication doses taken throughout the day had a moderate correlation with the difference between clinic and home. Performing a cycle-by-cycle analysis on gait speed during the home assessment, overall only about 3% of the strides had equal or greater gait speeds than the patients’ capacity in the clinic. These strides were during long walking bouts (>1 min) and happened before noon, around 26 min after medication intake, reaching their maximum occurrence probability 3 h after Levodopa intake. These results open the possibility of better control of medication intake in PD by considering both functional capacity and continuous monitoring of gait speed during real-life conditions.