Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

BACKGROUND: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. METHODS: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). RESULTS: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. CONCLUSION: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.

New methods for the assessment of Parkinson's disease (2005 to 2015): A systematic review.

BACKGROUND: The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinson's disease with technology (NAM-PD) in laboratory, clinical, and home environments. However, the current state of NAM-PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated. METHODS: A systematic review of articles published in the field from 2005 to 2015 was performed. Of 9,503 publications identified in PubMed and the Web of Science, 848 full papers were evaluated, and 588 original articles were assessed to evaluate the technological, demographic, clinimetric, and technology transfer readiness parameters of NAM-PD. RESULTS: Of the studies, 65% included fewer than 30 patients, < 50% employed a standard methodology to validate diagnostic tests, 8% confirmed their results in a different dataset, and 87% occurred in a clinic or lab. The axial features domain was the most frequently studied, followed by bradykinesia. Rigidity and nonmotor domains were rarely investigated. Only 6% of the systems reached a technology level that justified the hope of being included in clinical assessments in a useful time period. CONCLUSIONS: This systematic evaluation provides an overview of the current options for quantitative assessment of PD and what can be expected in the near future. There is a particular need for standardized and collaborative studies to confirm the results of preliminary initiatives, assess domains that are currently underinvestigated, and better validate the existing and upcoming NAM-PD. © 2016 International Parkinson and Movement Disorder Society.

[Musculoskeletal injections during the GP residency; deliberations of GP residents on the administration of musculoskeletal injections]. / Musculoskeletale injecties in de huisartsopleiding.

OBJECTIVE: Musculoskeletal injections can alleviate pain in certain problems of the musculoskeletal system. A significant part of general practitioners (GPs) does not feel competent to administer these injections while it is also known that medical residents of several specialties lack confidence in surgical and other technical skills. However, it is not known whether GP residents feel competent in these skills at the end of their residency and which factors are associated with this self-assessed competence. METHOD: To find out how GP residents think about musculoskeletal injections, twenty Dutch GP residents were interviewed in their final year using semi-structured interview techniques. These interviews were analyzed using template analysis. RESULTS: GP residents often experience a certain reluctance in the administration of musculoskeletal injections even though they mostly find that these injections do belong in primary care. The most named barriers are a low self-assessed competence and fear of septic arthritis, while other factors relate to the resident (confidence, coping style, and views on the specialty), the supervisor (their attitude), the patient (their situation and preferences), the injection (feasibility and estimated effectiveness) and the practice organization (office hours). CONCLUSION: GP residents consider many factors in their decision to administer musculoskeletal injections, most importantly their own competence and a fear of complications. Medical departments can help their residents through education on the decision-making process and the risks of certain interventions and provide opportunities to improve specific technical skills.

Algorithm for Turning Detection and Analysis Validated under Home-Like Conditions in Patients with Parkinson's Disease and Older Adults using a 6 Degree-of-Freedom Inertial Measurement Unit at the Lower Back.

INTRODUCTION: Aging and age-associated disorders such as Parkinson's disease (PD) are often associated with turning difficulties, which can lead to falls and fractures. Valid assessment of turning and turning deficits specifically in non-standardized environments may foster specific treatment and prevention of consequences. METHODS: Relative orientation, obtained from 3D-accelerometer and 3D-gyroscope data of a sensor worn at the lower back, was used to develop an algorithm for turning detection and qualitative analysis in PD patients and controls in non-standardized environments. The algorithm was validated with a total of 2,304 turns ≥90° extracted from an independent dataset of 20 PD patients during medication ON- and OFF-conditions and 13 older adults. Video observation by two independent clinical observers served as gold standard. RESULTS: In PD patients under medication OFF, the algorithm detected turns with a sensitivity of 0.92, a specificity of 0.89, and an accuracy of 0.92. During medication ON, values were 0.92, 0.78, and 0.83. In older adults, the algorithm reached validation values of 0.94, 0.89, and 0.92. Turning magnitude (difference, 0.06°; SEM, 0.14°) and duration (difference, 0.004 s; SEM, 0.005 s) yielded high correlation values with gold standard. Overall accuracy for direction of turning was 0.995. Intra class correlation of the clinical observers was 0.92. CONCLUSION: This wearable sensor- and relative orientation-based algorithm yields very high agreement with clinical observation for the detection and evaluation of ≥90° turns under non-standardized conditions in PD patients and older adults. It can be suggested for the assessment of turning in daily life.

Evidence for a Selectively Regulated Prioritization Shift Depending on Walking Situations in Older Adults.

Background: Older adults have increased risks of balance issues and falls when walking and performing turns in daily situations. Changes of prioritization during different walking situations associated with dual tasking may contribute to these deficits. The objective of this study was therefore to investigate whether older adults demonstrate changes of prioritization during different walking paths. Methods: In total, 1,054 subjects with an age range from 50 to 83 years were selected from the first follow-up visit of the TREND (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders) study. They were classified according to their performance on the Trail Making Test (TMT) into good and poor TMT performers (based on recent results showing that cognitive flexibility affects prioritization strategies during straight walking). Absolute dual-task performance and relative dual-task costs (DTC, relative performance under dual-task conditions compared with single-task conditions) were assessed in two paradigms: walking while subtracting serial 7 s and walking while checking boxes on a clipboard. Both tasks were performed on straight and curved paths. Results: Overall, the poor TMT performers group performed worse in all single and dual tasks. Interestingly, the relative change in performance measured by dual-task costs differed in the groups between the two walking paths. On straight paths, poor TMT performers had a similar DTC of walking to that of good performers (p = 0.10) but had a significantly lower DTC of subtracting (p = 0.02). On curved paths, poor performers had a similar DTC of subtracting (p = 0.10), but their DTC of walking was significantly higher (p < 0.0001). Conclusion: Given that walking on curved paths is considered more difficult than that on straight paths and that the serial subtracting dual task is more difficult than the box checking dual task, this study in older adults provides evidence for the existence of a (walking) situation-dependent change of prioritization. If confirmed in other studies, situation-dependent change of prioritization should be included as a potential factor contributing to gait and balance impairments, and increased fall risk in older adults.

Validation of a Step Detection Algorithm during Straight Walking and Turning in Patients with Parkinson's Disease and Older Adults Using an Inertial Measurement Unit at the Lower Back.

INTRODUCTION: Inertial measurement units (IMUs) positioned on various body locations allow detailed gait analysis even under unconstrained conditions. From a medical perspective, the assessment of vulnerable populations is of particular relevance, especially in the daily-life environment. Gait analysis algorithms need thorough validation, as many chronic diseases show specific and even unique gait patterns. The aim of this study was therefore to validate an acceleration-based step detection algorithm for patients with Parkinson's disease (PD) and older adults in both a lab-based and home-like environment. METHODS: In this prospective observational study, data were captured from a single 6-degrees of freedom IMU (APDM) (3DOF accelerometer and 3DOF gyroscope) worn on the lower back. Detection of heel strike (HS) and toe off (TO) on a treadmill was validated against an optoelectronic system (Vicon) (11 PD patients and 12 older adults). A second independent validation study in the home-like environment was performed against video observation (20 PD patients and 12 older adults) and included step counting during turning and non-turning, defined with a previously published algorithm. RESULTS: A continuous wavelet transform (cwt)-based algorithm was developed for step detection with very high agreement with the optoelectronic system. HS detection in PD patients/older adults, respectively, reached 99/99% accuracy. Similar results were obtained for TO (99/100%). In HS detection, Bland-Altman plots showed a mean difference of 0.002 s [95% confidence interval (CI) -0.09 to 0.10] between the algorithm and the optoelectronic system. The Bland-Altman plot for TO detection showed mean differences of 0.00 s (95% CI -0.12 to 0.12). In the home-like assessment, the algorithm for detection of occurrence of steps during turning reached 90% (PD patients)/90% (older adults) sensitivity, 83/88% specificity, and 88/89% accuracy. The detection of steps during non-turning phases reached 91/91% sensitivity, 90/90% specificity, and 91/91% accuracy. CONCLUSION: This cwt-based algorithm for step detection measured at the lower back is in high agreement with the optoelectronic system in both PD patients and older adults. This approach and algorithm thus could provide a valuable tool for future research on home-based gait analysis in these vulnerable cohorts.

A Viewpoint on Wearable Technology-Enabled Measurement of Wellbeing and Health-Related Quality of Life in Parkinson's Disease.

In this viewpoint, we discuss how several aspects of Parkinson's disease (PD) - known to be correlated with wellbeing and health-related quality of life-could be measured using wearable devices ('wearables'). Moreover, three people with PD (PwP) having exhaustive experience with using such devices write about their personal understanding of wellbeing and health-related quality of life, building a bridge between the true needs defined by PwP and the available methods of data collection. Rapidly evolving new technologies develop wearables that probe function and behaviour in domestic environments of people with chronic conditions such as PD and have the potential to serve their needs. Gathered data can serve to inform patient-driven management changes, enabling greater control by PwP and enhancing likelihood of improvements in wellbeing and health-related quality of life. Data can also be used to quantify wellbeing and health-related quality of life. Additionally these techniques can uncover novel more sensitive and more ecologically valid disease-related endpoints. Active involvement of PwP in data collection and interpretation stands to provide personally and clinically meaningful endpoints and milestones to inform advances in research and relevance of translational efforts in PD.