Dual tasking in Parkinson's disease: cognitive consequences while walking

Published in final edited form as: Neuropsychology. 2017 September; 31(6): 613–623. doi:10.1037/neu0000331.OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) and exacerbate the functional limitations imposed by PD's hallmark motor symptoms, including impairments in walking. Though much research has addressed the effect of dual cognitive-locomotor tasks on walking, less is known about their effect on cognition. The purpose of this study was to investigate the relation between gait and executive function, with the hypothesis that dual tasking would exacerbate cognitive vulnerabilities in PD as well as being associated with gait disturbances. METHOD: Nineteen individuals with mild-moderate PD without dementia and 13 age- and education-matched normal control adults (NC) participated. Executive function (set-shifting) and walking were assessed singly and during dual tasking. RESULTS: Dual tasking had a significant effect on cognition (reduced set-shifting) and on walking (speed, stride length) for both PD and NC, and also on stride frequency for PD only. The impact of dual tasking on walking speed and stride frequency was significantly greater for PD than NC. Though the group by condition interaction was not significant, PD had fewer set-shifts than NC on dual task. Further, relative to NC, PD showed significantly greater variability in cognitive performance under dual tasking, whereas variability in motor performance remained unaffected by dual tasking. CONCLUSIONS: Dual tasking had a significantly greater effect in PD than in NC on cognition as well as on walking. The results suggest that assessment and treatment of PD should consider the cognitive as well as the gait components of PD-related deficits under dual-task conditions. (PsycINFO Database Record)

Imposed faster and slower walking speeds influence gait stability differently in Parkinson fallers

Objective To evaluate the effect of imposed faster and slower walking speeds on postural stability in people with Parkinson disease (PD). Design Cross-sectional cohort study. Setting General community. Participants Patients with PD (n=84; 51 with a falls history; 33 without) and age-matched controls (n=82) were invited to participate via neurology clinics and preexisting databases. Of those contacted, 99 did not respond (PD=36; controls=63) and 27 were not interested (PD=18; controls=9). After screening, a further 10 patients were excluded; 5 had deep brain stimulation surgery and 5 could not accommodate to the treadmill. The remaining patients (N=30) completed all assessments and were subdivided into PD fallers (n=10), PD nonfallers (n=10), and age-matched controls (n=10) based on falls history. Interventions Not applicable. Main Outcome Measures Three-dimensional accelerometers assessed head and trunk accelerations and allowed calculation of harmonic ratios and root mean square (RMS) accelerations to assess segment control and movement amplitude. Results Symptom severity, balance confidence, and medical history were established before participants walked on a treadmill at 70%, 100%, and 130% of their preferred speed. Head and trunk control was lower for PD fallers than PD nonfallers and older adults. Significant interactions indicated head and trunk control increased with speed for PD nonfallers and older adults, but did not improve at faster speeds for PD fallers. Vertical head and trunk accelerations increased with walking speed for PD nonfallers and older adults, while the PD fallers demonstrated greater anteroposterior RMS accelerations compared with both other groups. Conclusions The results suggest that improved gait dynamics do not necessarily represent improved walking stability, and this must be respected when rehabilitating gait in patients with PD

Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

Using Kinect to classify Parkinson’s disease stages related to severity of gait impairment

Published: 10 December 2018Parkinson’s Disease (PD) is a chronic neurodegenerative disease associated with motor problems such as gait impairment. Different systems based on 3D cameras, accelerometers or gyroscopes have been used in related works in order to study gait disturbances in PD. Kinect Ⓡ has also been used to build these kinds of systems, but contradictory results have been reported: some works conclude that Kinect does not provide an accurate method of measuring gait kinematics variables, but others, on the contrary, report good accuracy results.This research work was funded by the Spanish Ministry of Economy and Competitiveness (grant FEDER/TIN2016-78011-C4-2-R). The funding bodies had no role in the design or conclusions of this study

Quantification of upper body movements during gait in older adults and in those with Parkinson's disease: impact of acceleration realignment methodologies.

The upper body accelerations of people with Parkinson’s disease (PD) measured by inertial measurement units (IMUs) may contribute towards diagnostic algorithms and help track disease progression. Before extracting variables related to upper body motion, acceleration signals require realignment to a global reference; however, the impact of these techniques on the resulting upper body variables is unclear. Therefore, the aim of this investigation was to examine the impact of four different realignment methods designed to correct acceleration signals on a range of upper body variables in older adults and in patients with PD. Two minutes of continuous gait were measured in 54 community-dwelling older adults (71.1 �6.7 years) and 60 people with PD (age: 68.5 � 9.1 years). Three IMUs placed on the 5th lumbar vertebra, 7th cervical vertebra and the back of the head recorded the acceleration of the upper body. A selection of upper body variables sensitive to impaired upper body control in PD and four acceleration realignment methods were compared. A mixed-model ANOVA showed that the choice of realignment method significantly affected the values of upper body variables as well as their ability to discriminate between the PD and control group. Our findings indicate researchers and clinicians should be cautious when comparing upper body variables extracted from IMUs using different realignment methods, and consideration of realignmenttechnique will be important when identifying the most sensitive markers of disease presence and progression. Therefore, it’s strongly recommend that researchers consider and report their realignment methods when assessing upper body variables during gai

Effects of personal and task constraints on limb coordination during walking: a systematic review and meta-analysis

Background In human behaviour, emergence of movement patterns is shaped by different, interacting constraints and consequently, individuals with motor disorders usually display distinctive lower limb coordination modes. Objectives To review existing evidence on the effects of motor disorders and different task constraints on emergent coordination patterns during walking, and to examine the clinical significance of task constraints on gait coordination in people with motor disorders. Methods The search included CINHAL Plus, MEDLINE, HSNAE, SPORTDiscus, Scopus, Pubmed and AMED. We included studies that compared intra-limb and inter-limb coordination during gait between individuals with a motor disorder and able-bodied individuals, and under different task constraints. Two reviewers independently examined the quality of studies by using the Newcastle Ottawa Scale-cohort study. Findings From the search results, we identified1416 articles that studied gait patterns and further analysis resulted in 33 articles for systematic review and 18 articles for meta-analysis-1, and 10 articles for meta-analysis-2. In total, the gait patterns of 539 patients and 358 able-bodied participants were analysed in the sampled studies. Results of the meta-analysis for group comparisons revealed a low effect size for group differences (ES = −0.24), and a moderate effect size for task interventions (ES = −0.53), on limb coordination during gait. Interpretation Findings demonstrated that motor disorders can be considered as an individual constraint, significantly altering gait patterns. These findings suggest that gait should be interpreted as functional adaptation to changing personal constraints, rather than as an abnormality. Results imply that designing gait interventions, through modifying locomotion tasks, can facilitate the emergent re-organisation of inter-limb coordination patterns during rehabilitation

Advanced technologies for axial impairment in Parkinson's disease: from early detection to outcome prediction

Axial motor symptoms—such as balance, gait, posture, and speech disorders—mark a critical milestone in the progression of Parkinson's disease (PD), significantly affecting patients’ prognosis and quality of life. However, the long-term evolution of these symptoms, especially in patients undergoing advanced therapies like subthalamic nucleus deep brain stimulation (STN-DBS), remains poorly understood. Also, current clinical evaluations lack sensitivity in detecting axial disorders at their early stages, and reliable predictors for patients at increased risk of developing these symptoms are still largely unknown. Recent technological advances in invasive neuromodulation (e.g., DBS), wearable sensors, and artificial intelligence-based computational methods provide new opportunities to address these challenges. This Thesis presents the main scientific findings from the PhD program, centred on the clinical and instrumental evaluation of axial impairment in PD using advanced technologies. The first section of the Thesis examines the short- and long-term clinical progression of axial disorders in a cohort of advanced PD patients treated with STN-DBS. Through a retrospective longitudinal analysis, a gradual worsening of axial symptoms, along with complications such as falls, was demonstrated over a period of up to 15 years post-surgery. The second section explores the use of wearable inertial and electromyographic sensors to assess gait and balance disorders in laboratory and home settings. These technologies accurately captured patient movement and quantified axial disturbances, highlighting their potential for telemedicine applications. Additionally, artificial intelligence algorithms were applied to automatically analyse speech in STN-DBS patients, revealing the impact of this therapy on vocal functions. In the third section, longitudinal regression analyses of a large PD cohort identified specific clinical predictors of axial symptoms, offering insight into patients at higher risk of developing related complications. A single wearable sensor was also used to accurately predict gait and balance impairments, demonstrating its utility for enhancing remote clinical assessments. In conclusion, the present Thesis underscores the potential of innovative monitoring and management strategies that leverage advanced technologies to improve clinical practice in PD

Advances in non-dopaminergic treatments for Parkinson's disease

Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. © 2014 Stayte and Vissel

Postural automatisms and biomechanics of gait initiation and obstacle negotiation in parkinson’s disease : characterization and effects of different interventions

A doença de Parkinson (DP) é uma doença neurodegenerativa relacionada à perda da independência funcional, com fenômenos motores, como rigidez, desequilíbrio e alterações na marcha. Os automatismos posturais, incluindo os ajustes posturais antecipatórios (APA) e compensatórios (CPA) são essenciais para o equilíbrio em resposta a uma perturbação e seu uso eficiente pode reduzir a ocorrência de quedas em tarefas cotidianas, como iniciação da marcha e negociação de obstáculos. Evidências apontam os benefícios de programas de exercícios na melhora da locomoção e controle postural na DP, entretanto, poucos estudos investigaram os efeitos sobre os automatismos posturais. Assim, a presente dissertação tem o objetivo de caracterizar as estratégias de automatismos posturais e comportamento motor relacionados à iniciação da marcha e negociação de obstáculos de pessoas com DP e comparar os efeitos de três programas de treinamento sobre esses parâmetros. No capítulo I é feita a apresentação geral e contextualização do estudo. No capítulo II é apresentada uma revisão de literatura, com informações compiladas sobre a DP, os automatismos posturais, a locomoção e como diferentes intervenções podem auxiliar na melhora dos parâmetros alterados. As lacunas identificadas na literatura motivaram a escrita de dois estudos originais. Os objetivos dos estudos foram: 1) analisar e comparar os ajustes posturais e os parâmetros biomecânicos durante a iniciação da marcha e negociação de obstáculos de pessoas com DP rígido-acinética e hipercinética; e 2) analisar e comparar os efeitos de três programas baseados em exercício físico (dança, exercícios em água funda e caminhada Nórdica) sobre os ajustes posturais e os parâmetros biomecânicos na iniciação da marcha e negociação de obstáculos em pessoas com DP. No estudo 1, foram avaliadas, de forma transversal, pessoas com DP divididas por subtipos clínicos (rígidos-acinéticos e hipercinéticos). Para o estudo 2, um ensaio clínico, estes sujeitos foram randomizados em três grupos de intervenção de 22 sessões, sendo avaliados antes e depois. Em ambos os estudos as avaliações incluíram variáveis eletromiográficas, cinéticas e cinemáticas. No estudo I, observamos que o grupo rígido-acinético apresentou maior comprometimento neuromotor, refletido por menor ação antecipatória e compensatória de músculos estabilizadores, menor deslocamento do centro de pressão, maior tempo de duplo apoio e menores comprimento e altura de passo durante as tarefas. Além disso, no estudo II as três intervenções mostraram melhoras nos parâmetros avaliados, sendo mais evidentes nos parâmetros espaço-temporais e músculos de tronco para exercícios em água funda e caminhada Nórdica, enquanto que a Dança promoveu melhores resultados na ação dos músculos de quadril. Nossos resultados são importantes para entender as diferenças no controle motor de pacientes com diferentes manifestações clínicas da DP e para auxiliar na prescrição de programas terapêuticos. Ainda, sugerimos que as três intervenções propostas possuem potencial para a manutenção e melhora neuromotora de pessoas com DP.Parkinson's disease (PD) is a neurodegenerative disease related to loss of functional independence, with motor phenomena such as rigidity, imbalance and changes in gait. Postural automatisms, including anticipatory (APA) and compensatory (CPA) postural adjustments are essential for balance in response to a disturbance and their effective use can reduce the occurrence of falls in everyday tasks, such as gait initiation and obstacle negotiation. Evidence points to the benefits of exercise programs in improving locomotion and postural control in PD, however, few studies have investigated the effects on postural automatisms. Thus, the present dissertation aims to characterize the strategies of postural automatisms and motor behavior related to the gait initiation and obstacle negotiation in people with PD and to compare the effects of three training programs on these parameters. Chapter I presents the general presentation and context of the study. Chapter II presents a literature review, with information compiled about PD, postural automatisms, locomotion and how different interventions can help to improve altered parameters. The gaps identified in the literature motivated the writing of two original studies. The aims of the studies were: 1) to analyze and compare postural adjustments to biomechanical parameters during gait initiation and obstacle negotiation in people with akinetic-rigid (AK-R) and hyperkinetic (HYP) PD; and 2) to analyze and compare the effects of three programs based on physical exercise (Brazilian dance, deep water exercises and Nordic walking) on postural adjustments and biomechanical parameters in gait initiation and obstacle negotiation in people with PD. In study 1, people with PD divided by clinical subtypes (AK-R and HYP) were evaluated in a cross-sectional research. . For study 2, a clinical trial, these subjects were randomized into three intervention groups of 22 sessions, being assessed pre and post. In both studies, evaluations included electromyographic, kinetic and kinematic variables. In study I, we observed that the AK-R group showed greater neuromotor impairment, reflected by less anticipatory and compensatory action of stabilizing muscles, less displacement of the center of pressure, longer double support time and shorter step length and height during tasks. Furthermore, in study II, the three interventions showed improvements in the parameters evaluated, being more evident in spatiotemporal parameters and trunk muscles for deep water exercises and Nordic walking, while dance promoted better results in the action of the hip muscles. Our results are important to understand the differences in motor control of patients with different clinical manifestations of PD and to assist in the prescription of therapeutic programs. In addition, we suggest that the three proposed interventions have the potential to maintain and improve neuromotor performance in people with PD