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BACKGROUND: In 2015, the International Parkinson and Movement Disorder Society Task Force recommended research criteria for the estimation of prodromal PD. OBJECTIVES: We aimed to evaluate, for the first time, the criteria in first-degree relatives of Ashkenazi Jewish G2019S-LRRK2 PD patients, who are considered a population at risk for developing PD, and assess the sensitivity and specificity of the criteria in identifying phenoconverters. METHODS: Participants were evaluated longitudinally over a period of 5 years (average follow-up: 49.2 ± 12.3 months). Likelihood ratios and probability estimations were calculated based on the International Parkinson and Movement Disorder Society Research Criteria for Prodromal Parkinson's Disease markers and examined for each assessment point. RESULTS: One hundred twenty healthy carriers (49.53 ± 13.4 years; 54% female) and 111 healthy noncarriers (48.43 ± 15.79 years; 49% female) participated in this study. Probability scores were significantly higher in healthy carriers than healthy noncarriers (P < 0.0001). Of the 20 participants (8.6%) who met criteria for probable prodromal PD at baseline, 17 were healthy carriers. Participants who reached the threshold were older (P < 0.0001), had higher UPDRS-III (P < 0.001), lower cognitive function (P = 0.001), and more nonmotor symptoms (P < 0.0001), compared to those who did not. Ten participants were diagnosed with incident PD within 5 years from baseline resulting in a specificity of 91.82% (95% confidence interval: 86.69-96.94), sensitivity of 80% (95% confidence interval: 55.21-100), positive predictive value of 47.06% (95% confidence interval: 23.33-70.79), and negative predictive value of 98.06% (95% confidence interval: 95.39-100). All 10 phenoconvertors were G2019S-LRRK2 carriers. CONCLUSIONS: The results showed the utility of using the criteria and high sensitivity and specificity in identifying prodromal PD in this high-risk unique cohort. These results may be valuable for future disease modification clinical trials. © 2018 International Parkinson and Movement Disorder Society.
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Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/genética , Mutación/genética , Síntomas Prodrómicos , Sociedades Médicas/normas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glicina/genética , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Serina/genética , Adulto JovenRESUMEN
BACKGROUND: Obstacle negotiation is a daily activity that requires the integration of sensorimotor and cognitive information. Recent studies provide evidence for the important role of prefrontal cortex during obstacle negotiation. We aimed to explore the effects of obstacle height and available response time on prefrontal activation. METHODS: Twenty healthy young adults (age: 30.1⯱â¯1.0â¯years; 50% women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 50â¯mm and 100â¯mm. Prefrontal activation was measured using a functional near-infrared spectroscopy system. Kinect cameras measured the obstacle negotiation strategy. Prefrontal activation was defined based on mean level of HbO2 before, during and after obstacle negotiation and the HbO2 slope from gait initiation and throughout the task. Changes between types of obstacles were assessed using linear-mix models and partial correlation analyses evaluated the relationship between prefrontal activation and the distance between the feet as the subjects traversed the obstacles. RESULTS: Different obstacle heights showed similar changes in prefrontal activation measures (pâ¯>â¯0.210). However, during unanticipated obstacles, the slope of the HbO2 response was steeper (pâ¯=â¯0.048), as compared to anticipated obstacles. These changes in prefrontal activation during negotiation of unanticipated obstacles were correlated with greater distance of the leading foot after the obstacles (râ¯=â¯0.831, pâ¯=â¯0.041). CONCLUSIONS: These findings are the first to show that the pattern of prefrontal activation depends on the nature of the obstacle. More specifically, during unanticipated obstacles the recruitment of the prefrontal cortex is faster and greater than during negotiating anticipated obstacles. These results provide evidence of the important role of the prefrontal cortex and the ability of healthy young adults to tailor the activation pattern to different types of obstacles.
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Marcha/fisiología , Corteza Prefrontal/fisiología , Caminata/fisiología , Adulto , Femenino , Neuroimagen Funcional , Humanos , Masculino , Corteza Prefrontal/diagnóstico por imagen , Tiempo de Reacción/fisiología , Espectroscopía Infrarroja CortaRESUMEN
OBJECTIVE: To investigate EEG changes during an auditory odd-ball task while walking (dual-task) in young adults, older adults, and patients with Parkinson's disease. METHODS: 11 young adults, 10 older adults, and 10 patients with Parkinson's disease (PD) performed an auditory oddball task during standing and walking on a treadmill, while wearing a wireless EEG cap. The amplitude and latency of P300 were compared between groups and within conditions using linear mix model analysis. Gait was evaluated using wearable sensors and cognition was assessed using the Color Trail Test. RESULTS: P300 latency became longer during walking in all groups (pâ¯=â¯0.005). During walking, older adults (pâ¯=â¯0.005) and patients with PD (pâ¯=â¯0.001) showed prolonged P300 latency compared to young adults. Significant task by group interaction was found in P300 amplitude (pâ¯=â¯0.008). Patients with PD demonstrated reduced P300 amplitude during walking compared to standing (pâ¯=â¯0.023). Among all subjects, better motor and cognitive performance correlated with shorter P300 latency (râ¯=â¯0.457, pâ¯=â¯0.014 and râ¯=â¯0.431, pâ¯=â¯0.040, respectively). CONCLUSIONS: These findings provide direct evidence of the physiological recruitment of attentional networks during walking and their impact by ageing and disease. SIGNIFICANCE: This study is the first to report on changes in P300 latency and amplitude during dual-task oddball walking in older adults and patients with PD.
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Envejecimiento/fisiología , Percepción Auditiva/fisiología , Potenciales Relacionados con Evento P300/fisiología , Enfermedad de Parkinson/fisiopatología , Caminata/fisiología , Estimulación Acústica/métodos , Adulto , Anciano , Envejecimiento/psicología , Electroencefalografía/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/psicología , Distribución Aleatoria , Caminata/psicologíaRESUMEN
OBJECTIVE: Circadian and sleep dysfunction have long been symptomatic hallmarks of a variety of devastating neurodegenerative conditions. The gold standard for sleep monitoring is overnight sleep in a polysomnography (PSG) laboratory. However, this method has several limitations such as availability, cost and being labour-intensive. In recent years there has been a heightened interest in home-based sleep monitoring via wearable sensors. Our objective was to demonstrate the use of printed electrode technology as a novel platform for sleep monitoring. APPROACH: Printed electrode arrays offer exciting opportunities in the realm of wearable electrophysiology. In particular, soft electrodes can conform neatly to the wearer's skin, allowing user convenience and stable recordings. As such, soft skin-adhesive non-gel-based electrodes offer a unique opportunity to combine electroencephalography (EEG), electromyography (EMG), electrooculography (EOG) and facial EMG capabilities to capture neural and motor functions in comfortable non-laboratory settings. In this investigation temporary-tattoo dry electrode system for sleep staging analysis was designed, implemented and tested. MAIN RESULTS: EMG, EOG and EEG were successfully recorded using a wireless system. Stable recordings were achieved both at a hospital environment and a home setting. Sleep monitoring during a 6 h session shows clear differentiation of sleep stages. SIGNIFICANCE: The new system has great potential in monitoring sleep disorders in the home environment. Specifically, it may allow the identification of disorders associated with neurological disorders such as rapid eye movement (REM) sleep behavior disorder.
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Electroencefalografía/métodos , Electromiografía/métodos , Electrooculografía/métodos , Polisomnografía/métodos , Fases del Sueño/fisiología , Tatuaje/métodos , Adulto , Electrodos , Electroencefalografía/instrumentación , Electromiografía/instrumentación , Electrooculografía/instrumentación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/métodos , Polisomnografía/instrumentación , Tatuaje/instrumentación , Dispositivos Electrónicos VestiblesRESUMEN
BACKGROUND: Among patients with Parkinson's disease (PD), gait is typically disturbed and less automatic. These gait changes are associated with impaired rhythmicity and increased prefrontal activation, presumably in an attempt to compensate for reduced automaticity. RESEARCH QUESTION: We investigated whether during treadmill walking, when the pace is determined and fixed, prefrontal activation in patients with PD is lower, as compared to over-ground walking. METHODS: Twenty patients with PD (age: 69.8⯱â¯6.5 yrs.; MoCA: 26.9⯱â¯2.4; disease duration: 7.9⯱â¯4.2 yrs) walked at a self-selected walking speed over-ground and on a treadmill. A wireless functional near infrared spectroscopy (fNIRS) system measured prefrontal lobe activation, i.e., oxygenated hemoglobin (Hb02) in the pre-frontal area. Gait was evaluated using 3D-accelerometers attached to the lower back and ankles (Opal™, APDM). Dynamic gait stability was assessed using the maximum Lyapunov exponent to investigate automaticity of the walking pattern. RESULTS: Hb02 was lower during treadmill walking than during over-ground walking (pâ¯=â¯0.001). Gait stability was greater on the treadmill, compared to over-ground walking, in both the anteroposterior and medio-lateral axes (pâ¯<â¯0.001). SIGNIFICANCE: These findings support the notion that when gait is externally paced, prefrontal lobe activation is reduced in patients with PD, perhaps reflecting a reduced need for compensatory cognitive mechanisms.
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Lóbulo Frontal/fisiopatología , Marcha/fisiología , Enfermedad de Parkinson/fisiopatología , Modalidades de Fisioterapia , Velocidad al Caminar/fisiología , Anciano , Anciano de 80 o más Años , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/rehabilitaciónRESUMEN
Background: Recent work demonstrated that the gait of people with mild cognitive impairment (MCI) differs from that of age-matched controls and, in general, that walking ability, as measured in the clinic, does not necessarily reflect actual, daily performance. We evaluated if the quantity and quality of everyday walking (ie, community ambulation) differs in older adults with MCI, compared to age-matched controls. Methods: Inclusion criteria included: age 65-90 years, able to walk at least 5 minutes unassisted, and ≥2 falls in the past 6 months. Subjects with MCI were included if they scored 0.5 on the Clinical Dementia Rating Scale. To assess stepping quantity and quality, subjects wore a tri-axial accelerometer on the lower-back for 7 days. Results: Age and gender were similar (p > .10) in MCI (n = 36, 77.8 ± 6.4 years; 27.8% men) and controls (n = 100, 76.0 ± 6.2 years; 22.0% men). As expected, Montreal Cognitive Assessment scores were lower (p < .001) in MCI (21.31 ± 4.05), compared to controls (25.81 ± 2.64). Walking time was lower (p = .016) in MCI (0.74 ± 0.48 hours/d), compared to controls (1.05 ± 0.66 hours/d). Within-bout walking (eg, stride regularity) was less consistent (p = .024) in MCI (0.51 ± 0.14), compared to controls (0.58 ± 0.14). Changes in stride regularity across bouts were lower (p < .001) in MCI (0.13 ± 0.04), compared to controls (0.17 ± 0.01). Conclusions: Older adults with MCI walk less and with a more variable within-bout and less variable across-bout walking pattern, as compared to cognitively-intact subjects matched with respect to age and gender. These findings extend previous clinical work and suggest that MCI affects both the quantity and quality of community ambulation.