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INTRODUCTION: Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism's physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson's Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing. METHODS AND ANALYSIS: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringâ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways. DISCUSSION: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes.
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Relojes Circadianos , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Relojes Circadianos/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Saliva/metabolismo , Ritmo Circadiano/genética , Estudios de Casos y Controles , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Adulto , PolisomnografíaRESUMEN
BACKGROUND: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. METHODS: Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. RESULTS: Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were the most interesting characteristics for future analysis. CONCLUSIONS: Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue.
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Fatiga , Estudios de Factibilidad , Marcha , Fatiga Mental , Enfermedades Neurodegenerativas , Caminata , Humanos , Masculino , Femenino , Persona de Mediana Edad , Fatiga/diagnóstico , Fatiga/fisiopatología , Fatiga/etiología , Caminata/fisiología , Anciano , Fatiga Mental/fisiopatología , Fatiga Mental/diagnóstico , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/fisiopatología , Enfermedades Neurodegenerativas/diagnóstico , Marcha/fisiología , Dispositivos Electrónicos Vestibles , Enfermedades del Sistema Inmune/complicaciones , Enfermedades del Sistema Inmune/diagnóstico , Adulto , Acelerometría/instrumentación , Acelerometría/métodosRESUMEN
Introduction: Computer confidence and computer self-efficacy can impact an individual's perceived ease of use and usefulness of technology, ultimately determining adherence to digital healthcare services. However, few studies focus on assessing the impact of non-clinical factors on the efficacy and adherence to digital healthcare platforms. Objective: We aimed to analyse the role of non-clinical factors (i.e. computer confidence and computer self-efficacy) in the interaction experience (IX) and the feasibility of a digital neuropsychological platform called NeuroVRehab.PT in a group of older adults with varying levels of computer confidence. Methods: Eight older adults (70.63 ± 6.1 years) evaluated the platform, and data was collected using the Think-Aloud method and a semi-structured interview. Sessions were audio-recorded and analysed through an inductive-deductive informed Thematic Analysis protocol. This study was conducted according to the Consolidated Criteria for Reporting Qualitative Research guidelines. Results: Three main themes were identified (Interaction Experience, Digital Literacy, and Attitudes toward NeuroVRehab.PT). Computer anxiety and fear of making errors were not uncommon, even among older adults who perceive themselves as confident in technology use, and negatively impacted IX. Moreover, some game elements (e.g. three-star system, progression bar) were not intuitive to all participants, leading to misleading interpretations. On the other hand, human support and the platform's realism seemed to impact participants' IX positively. Conclusions: This study shed light on the barriers raised by non-clinical factors in adopting and using digital healthcare services by older adults. Furthermore, a critical analysis of the platform's features that promote user adoption is done, and suggestions for overcoming limitations are presented.
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Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs. To address walking bouts that were short and sparse, four feature groups were considered: sequence-independent variability (SIV), sequence-dependant variability (SDV), padded SDV (PSDV), and typical gait variability (TGV) measures. These gait variability measures were extracted from step, stride, stance, and swing time, step length, and step velocity. These different approaches were compared using correlations and four machine learning classifiers to separate low/high fatigue and sleepiness.Most balanced accuracies were above 50%, the highest was 57.04% from TGV measures. The strongest correlation was 0.262 from an SDV feature against sleepiness. Overall, TGV measures had lower correlations and classification accuracies.Identifying fatigue or sleepiness from gait variability is extremely complex and requires more investigation with a larger data set, but these measures have shown performances that could contribute to a larger feature set.Clinical relevance- Gait variability has been repeatedly used to assess fatigue in the lab. The current study, however, explores gait variability for fatigue and daytime sleepiness in real-world scenarios with multiple gait-impacted disorders.
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Trastornos de Somnolencia Excesiva , Fatiga , Marcha , Enfermedades del Sistema Inmune , Enfermedades Neurodegenerativas , Somnolencia , Humanos , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/etiología , Trastornos de Somnolencia Excesiva/fisiopatología , Fatiga/diagnóstico , Fatiga/etiología , Fatiga/fisiopatología , Marcha/fisiología , Enfermedades del Sistema Inmune/complicaciones , Enfermedades del Sistema Inmune/fisiopatología , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/fisiopatología , Somnolencia/fisiologíaRESUMEN
Introduction: The SmartFeeding4Kids (SF4K) program is an online self-guided intervention for parents with the propose of changing parental feeding practices and children's dietary intake, focusing on the intake of added sugars, fruit, vegetables, and legumes. This paper aims to describe children's dietary pattern at baseline through a 24-h food recall, the SmartKidsDiet24. Methods: Overall, 89 participants recorded at least one meal of the 3-day food recall. Mean age was 36.22 ± 6.05 years and 53.09 ± 15.42 months old for parents and children, respectively. Of these, 22 participants were considered to have 2 days of near complete 24-h food recalls. Children's dietary intake are reported for these 22 participants based on parents reports and, thus, represent estimations only, as it remains unknown whether children consumed other non-reported foods. Results: Fruit was the group with the highest daily intake among children (mean 1.77 ± 1.10 portions/day), followed by added sugar foods (mean 1.48 ± 0.89 portions/day), vegetables [median 1.27 (1.64) portions/day] and legumes [median 0.12 (0.39) portions/day]. Fruit intake was positively correlated with vegetable intake (p = 0.008). Regarding Dietary Reference Values accomplishment, 13.6% of children exceeded the daily safe and adequate intake of sodium, 77.3% did not meet potassium and fiber recommendations, and 31.8% did not meet vitamin C recommendations. Discussion: All children did not meet calcium, vitamin B12 and vitamin D intake recommendations. Our findings further justify the need for dietary interventions in this field, to improve young children's diets. Clinical trial registration: ClinicalTrials.gov, identifier NCT04591496.
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Drooling is a common symptom of Parkinson's Disease (PD) experienced in up to 70% of people with PD (PwP). Drooling can be a major problem in PwP leading to adverse physical and psychosocial issues. Current medical treatments decrease the production of saliva, whereas the problem is due to decreased swallowing frequency, not over production of saliva. Such treatments are problematic as saliva is essential for good oral health. Therefore, non-invasive treatments options such as behavioural cueing methods are recommended. A wrist-worn device delivering haptic cueing has been demonstrated to be an effective treatment method to increase swallowing frequency and a socially acceptable solution for PwP. However, the device had limited functionality and was tested on a small sample size over a short period of usage. Further work is required to understand the real-world behaviours and usage of the intervention to understand the longer-term effects with a larger sample size. This research will deploy CueBand, a discrete and comfortable wrist-worn device designed to work with a smartphone application to support the real-world evaluation of haptic cueing for the management of drooling. We will recruit 3,000 PwP to wear the device day and night for the intervention period to gain a greater understanding of the effectiveness and acceptability of the technology within real-world use. Additionally, 300 PwP who self-identity as having an issue with drooling will be recruited into an intervention study to evaluate the effectiveness of the wrist-worn CueBand to deliver haptic cueing (3-weeks) compared with smartphone cueing methods (3-weeks). PwP will use our smartphone application to self-assess their drooling frequency, severity, and duration using visual analogue scales and through the completion of daily diaries. Semi-structured interviews to gain feedback about utility of CueBand will be conducted following participants completion of the intervention.
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Enfermedad de Parkinson , Sialorrea , Dispositivos Electrónicos Vestibles , Humanos , Enfermedad de Parkinson/psicología , Saliva , DegluciónRESUMEN
There is growing interest in monitoring gait patterns in people with neurological conditions. The democratisation of wearable inertial sensors has enabled the study of gait in free living environments. One pivotal aspect of gait assessment in uncontrolled environments is the ability to accurately recognise gait instances. Previous work has focused on wavelet transform methods or general machine learning models to detect gait; the former assume a comparable gait pattern between people and the latter assume training datasets that represent a diverse population. In this paper, we argue that these approaches are unsuitable for people with severe motor impairments and their distinct gait patterns, and make the case for a lightweight personalised alternative. We propose an approach that builds on top of a general model, fine-tuning it with personalised data. A comparative proof-of-concept evaluation with general machine learning (NN and CNN) approaches and personalised counterparts showed that the latter improved the overall accuracy in 3.5% for the NN and 5.3% for the CNN. More importantly, participants that were ill-represented by the general model (the most extreme cases) had the recognition of gait instances improved by up to 16.9% for NN and 20.5% for CNN with the personalised approaches. It is common to say that people with neurological conditions, such as Parkinson's disease, present very individual motor patterns, and that in a sense they are all outliers; we expect that our results will motivate researchers to explore alternative approaches that value personalisation rather than harvesting datasets that are may be able to represent these differences.
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Marcha , Enfermedad de Parkinson , Humanos , Aprendizaje Automático , Enfermedad de Parkinson/diagnóstico , Prueba de Estudio Conceptual , Análisis de OndículasRESUMEN
BACKGROUND: Caregivers' influence on young children's eating behaviors is widely recognized. Nutritional interventions that focus on the promotion of children's healthy diet should actively involve parents, focusing on their feeding behaviors and practices. METHODS: This work aims to describe the development and study protocol of the SmartFeeding4Kids (SF4K) program, an online self-guided 7-session intervention for parents of young (2-6 years old) children. The program is informed by social cognitive, self-regulation, and habit formation theoretical models and uses self-regulatory techniques as self-monitoring, goal setting, and feedback to promote behavior change. We propose to examine the intervention efficacy on children's intake of fruit, vegetables, and added sugars, and parental feeding practices with a two-arm randomized controlled with four times repeated measures design (baseline, immediately, 3 and 6 months after intervention). Parental perceived barriers about food and feeding, food parenting self-efficacy, and motivation to change will be analyzed as secondary outcomes. The study of the predictors of parents' dropout rates and the trajectories of parents' and children's outcomes are also objectives of this work. DISCUSSION: The SmartFeeding4Kids program relies on technological resources to deliver parents' self-regulation techniques that proved effective in promoting health behaviors. The study design can enhance the knowledge about the most effective methodologies to change parental feeding practices and children's food intake. As a self-guided online program, SmartFeeding4Kids might overcome parents' attrition more effectively, besides being easy to disseminate and cost-effective. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov ( NCT04591496 ) on October 19, 2020.
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Dieta Saludable , Responsabilidad Parental , Niño , Preescolar , Conducta Alimentaria , Humanos , Padres , Ensayos Clínicos Controlados Aleatorios como Asunto , VerdurasRESUMEN
Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from -0.26 to 0.42). Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.
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Mild cognitive impairment (MCI) is characterized by cognitive, psychological, and functional impairments. Digital interventions typically focus on cognitive deficits, neglecting the difficulties that patients experience in instrumental activities of daily living (IADL). The global conjecture created by COVID-19 has highlighted the seminal importance of digital interventions for the provision of healthcare services. Here, we investigated the feasibility and rehabilitation potential of a new design approach for creating highly realistic interactive virtual environments for MCI patients' neurorehabilitation. Through a participatory design protocol, a neurorehabilitation digital platform was developed using images captured from a Portuguese supermarket (NeuroVRehab.PT). NeuroVRehab.PT's main features (e.g., medium-sized supermarket, the use of shopping lists) were established according to a shopping behavior questionnaire filled in by 110 older adults. Seven health professionals used the platform and assessed its rehabilitation potential, clinical applicability, and user experience. Interviews were conducted using the think-aloud method and semi-structured scripts, and four main themes were derived from an inductive semantic thematic analysis. Our findings support NeuroVRehab.PT as an ecologically valid instrument with clinical applicability in MCI neurorehabilitation. Our design approach, together with a comprehensive analysis of the patients' past experiences with IADL, is a promising technique to develop effective digital interventions to promote real-world functioning.
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BACKGROUND: Gait impairments are common and highly disabling for Parkinson's disease (PD) patients. With the development of technology-based tools, it is now possible to measure the spatiotemporal parameters of gait with a reduced margin of error, thereby enabling a more accurate characterization of impairment. OBJECTIVE: To summarize and critically appraise the characteristics of technology-based gait analysis in PD and to provide mean and standard deviation values for spatiotemporal gait parameters. METHODS: A systematic review was conducted using the databases CENTRAL, MEDLINE, Embase, and PEDro from their inception to September 2019 to identify all observational and experimental studies conducted in PD or atypical parkinsonism that included a technology-based gait assessment. Two reviewers independently screened citations and extracted data. RESULTS: We included 95 studies, 82.1% (nâ=â78) reporting a laboratory gait assessment and 61.1% (nâ=â58 studies) using a wearable sensor. The most frequently reported parameters were gait velocity, stride and step length, and cadence. A statistically significant difference was found when comparing the mean values of each of these parameters in PD patients versus healthy controls. No statistically significant differences were found in the mean value of the parameters when comparing wearable versus non-wearable sensors, different types of wearable sensors, and different sensor locations. CONCLUSION: Our results provide useful information for performing objective technology-based gait assessment in PD, as well as mean values to better interpret the results. Further studies should explore the clinical meaningfulness of each parameter and how they behave in a free-living context and throughout disease progression.
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Fenómenos Biomecánicos/fisiología , Marcha/fisiología , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural/fisiología , Dispositivos Electrónicos Vestibles/estadística & datos numéricos , Anciano , Femenino , Humanos , MasculinoRESUMEN
Restless legs syndrome (RLS) is a neurological disorder that responds to dopaminergic drugs, indicating a common pathophysiology with Parkinson's disease (PD). The prevalence of RLS was estimated in a group of PD patients and its clinical and biochemical characteristics were analysed. Forty-eight patients with PD were evaluated into two groups, with and without RLS. Clinical characteristics assessed in both groups were age, gender, duration of PD, Hoehn and Yahr, and Schwab and England scales. Laboratory variables such as hemoglobin, s-iron, s-ferritin and creatinine were obtained. The prevalence of RLS was 18.75 percent. No significant differences regarding clinical variables and biochemical parameters were observed. The high prevalence of RLS found in PD patients suggests the concept of a common etiological link and it seems that secondary causes did not play a central role in the pathophysiology of RLS in this group of parkinsonian patients.
A síndrome das pernas inquietas (SPI) é um distúrbio sensitivo-motor que responde aos agentes dopaminérgicos, demonstrando uma possível semelhança fisiopatológica com a doença de Parkinson (DP). Foi avaliada a prevalência da SPI em um grupo de pacientes com DP e suas características clínicas e laboratoriais. Quarenta e oito pacientes diagnosticados com DP foram divididos em dois grupos: com e sem SPI. Características clínicas como idade, sexo, duração da DP, escalas de Hoehn e Yahr, e Schwab e England e achados bioquímicos como hemoglobina, ferro sérico, ferritina sérica e creatinina foram obtidos. A freqüência da SPI foi de 18,75 por cento. Não se observaram diferenças estatisticamente significativas quanto às características clínicas e aos achados bioquímicos. A alta prevalência de SPI encontrada em pacientes com DP sugere associação entre essas duas doenças. É provável que causas secundárias não exerçam papel central na fisiopatologia da SPI nesse grupo de pacientes parkinsonianos.
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Síndrome de las Piernas Inquietas/complicaciones , Ferritinas/sangre , Hemoglobinas/análisis , Hierro/sangre , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/fisiopatología , Síndrome de las Piernas Inquietas/sangre , Síndrome de las Piernas Inquietas/fisiopatología , Urea/sangreRESUMEN
Restless legs syndrome (RLS) is a neurological disorder that responds to dopaminergic drugs, indicating a common pathophysiology with Parkinson's disease (PD). The prevalence of RLS was estimated in a group of PD patients and its clinical and biochemical characteristics were analysed. Forty-eight patients with PD were evaluated into two groups, with and without RLS. Clinical characteristics assessed in both groups were age, gender, duration of PD, Hoehn and Yahr, and Schwab and England scales. Laboratory variables such as hemoglobin, s-iron, s-ferritin and creatinine were obtained. The prevalence of RLS was 18.75%. No significant differences regarding clinical variables and biochemical parameters were observed. The high prevalence of RLS found in PD patients suggests the concept of a common etiological link and it seems that secondary causes did not play a central role in the pathophysiology of RLS in this group of parkinsonian patients.