RESUMEN
Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1â year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.
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Apatía , Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Enfermedad de Parkinson/complicaciones , Núcleo Subtalámico/fisiología , Apatía/fisiología , Estudios Prospectivos , Estimulación Encefálica Profunda/métodos , Cognición , Resultado del TratamientoRESUMEN
Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.
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Esclerosis Amiotrófica Lateral , Cafeína , Citocromo P-450 CYP1A2 , Progresión de la Enfermedad , Polimorfismo de Nucleótido Simple , Receptor de Adenosina A2A , Humanos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Receptor de Adenosina A2A/genética , Citocromo P-450 CYP1A2/genética , Cognición/fisiología , Cognición/efectos de los fármacos , Estudios Prospectivos , Citocromo P-450 CYP1A1/genética , Receptores de Hidrocarburo de Aril/genética , Adulto , Disfunción Cognitiva/genética , Riluzol/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Factores de Transcripción con Motivo Hélice-Asa-Hélice BásicoRESUMEN
BACKGROUND: Little is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition. OBJECTIVE: Our objective was to determine the frequency and severity of cognitive impairment in RFC1-positive patients and describe the pattern of deficits. METHODS: Participants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules was measured in those who underwent a 3 Tesla-magnetic resonance scan. RESULTS: Twenty-one patients underwent a complete assessment, including 71% scoring lower than the cutoff at the Montreal Cognitive assessment and 71% having a definite cerebellar cognitive affective/Schmahmann syndrome. Three patients had dementia and seven met the criteria of mild cognitive impairment. Severity of cognitive impairment did not correlate with severity of clinical manifestations. Performance at memory and visuospatial functions tests negatively correlated with the severity of cerebellar manifestations. CONCLUSION: Cognitive manifestations are frequent in RFC1-related disorders. They should be included in the phenotype and screened systematically. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Ataxia Cerebelosa , Disfunción Cognitiva , Fenotipo , Humanos , Femenino , Masculino , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Ataxia Cerebelosa/fisiopatología , Ataxia Cerebelosa/complicaciones , Persona de Mediana Edad , Anciano , Adulto , Pruebas Neuropsicológicas , Proteína de Replicación C/genética , Imagen por Resonancia Magnética , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Cerebelo/patología , Enfermedades Vestibulares/fisiopatologíaRESUMEN
The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/terapia , Medicina de Precisión , Progresión de la Enfermedad , Comités ConsultivosRESUMEN
BACKGROUND: The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. OBJECTIVE: The aim was to identify resting-state functional modifications associated with these subtypes. METHODS: Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. RESULTS: Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. CONCLUSION: MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. © 2021 International Parkinson and Movement Disorder Society.
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Disfunción Cognitiva , Enfermedad de Parkinson , Encéfalo/patología , Mapeo Encefálico , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patologíaRESUMEN
OBJECTIVE: Anxiety is a prominent concern in Parkinson's disease (PD) that negatively impacts quality of life, increases functional disability, and complicates clinical management. Atypical presentations of anxiety are under-recognized and inadequately treated in patients with PD, compromising global PD care. METHODS: This systematic review focuses on the prevalence, symptomology and clinical correlates of atypical presentations of PD-related anxiety following PRISMA guidelines. RESULTS: Of the 60 studies meeting inclusion criteria, 14 focused on 'Anxiety Not Otherwise Specified (NOS)' or equivalent, 31 reported on fluctuating anxiety symptoms, and 22 reported on 'Fear of Falling (FOF)'. Anxiety NOS accounted for a weighted mean prevalence of 14.9%, fluctuating anxiety for 34.19%, and FOF for 51.5%. These latter two exceeded the average reported overall prevalence rate of 31% for anxiety disorders in PD. We identified a diverse array of anxiety symptoms related to motor and non-motor symptoms of PD, to complications of PD medication (such as "on" and "off" fluctuations, or both), and, to a lesser extent, to cognitive symptoms. CONCLUSION: Atypical anxiety is common, clinically relevant, and heterogeneous in nature. A better understanding of the phenomenology, clinical course, and pathophysiology of varied forms of atypical anxiety in PD is needed to improve recognition, advance therapeutic development and ultimately optimize quality of life in PD.
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Enfermedad de Parkinson , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/epidemiología , Miedo/psicología , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Calidad de Vida/psicologíaRESUMEN
BACKGROUND: The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico-striato-thalamocortical circuit. METHODS: Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single-photon emission computed tomography were included. RESULTS: The severity of anxiety was associated with changes in the fear circuit and the cortico-striato-thalamocortical limbic circuit. In the fear circuit, a reduced gray-matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico-striato-thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported. CONCLUSION: To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico-striato-thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Amígdala del Cerebelo , Ansiedad/diagnóstico por imagen , Ansiedad/etiología , Trastornos de Ansiedad/diagnóstico por imagen , Trastornos de Ansiedad/etiología , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagenRESUMEN
BACKGROUND: Anxiety disorders are among the most prevalent and disabling neuropsychiatric syndromes in patients with Parkinson's disease (PD), but no randomized controlled treatment trials of anxiety have been published to date. OBJECTIVE: The aim of this study was to assess the effectiveness of cognitive behavioral therapy (CBT) in the treatment of anxiety in patients with PD. METHODS: Forty-eight patients with PD with anxiety were randomized 1:1 between CBT and clinical monitoring only (CMO). The CBT program was developed to specifically address anxiety symptoms in PD and consisted of 10 weekly sessions. Assessments were conducted by blinded assessors at baseline, at the end of the intervention, after 3 months, and after 6 months (CBT group only). Main outcome measures were the Hamilton Anxiety Rating Scale (HARS) and the Parkinson Anxiety Scale (PAS). RESULTS: Both the CBT and CMO groups showed clinically relevant improvement. Although there was no between-group difference in outcome on the Hamilton Anxiety Rating Scale (6.7-point reduction in the CBT group versus 3.9-point reduction in the CMO group; P = 0.15), there was both a statistically significant and a clinically relevant between-group difference on the total PAS in favor of CBT (9.9-point reduction in the CBT group versus 5.2-point reduction in the CMO group; P = 0.012), which was due to improvement on the PAS subscales for episodic (situational) anxiety and avoidance behavior. This greater improvement was maintained at 3- and 6-month follow-ups. CONCLUSION: CBT is an effective treatment for anxiety in patients with PD and reduces situational and social anxiety, as well as avoidance behavior. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Terapia Cognitivo-Conductual , Enfermedad de Parkinson , Ansiedad/etiología , Ansiedad/terapia , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/terapia , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Cognitive impairment is a frequent nonmotor symptom of Parkinson's disease. Depending on severity, patients are considered to have mild cognitive impairment or dementia. However, among the cognitively intact patients, some may have deficits in a less severe range. The early detection of such subtle symptoms may be important for the initiation of care strategies. OBJECTIVE: To identify imaging markers of early cognitive symptoms, potentially before usual signs, such as atrophy, become manifest. METHODS: A total of 102 patients with Parkinson's disease and 17 age-matched cognitively intact healthy controls underwent extensive neuropsychological assessment and T1-weighted magnetic resonance imaging. Parkinson's disease patients were separated into 3 groups according to their cognitive status: intact, with slight slowing, and with mild deficits in executive functions. Texture features as measured by first-order and second-order statistics were computed in the following 6 brain regions: the hippocampus, thalamus, amygdala, putamen, caudate nucleus, and pallidum. They were tested between the groups, and their correlation with cognition was examined. Volumetric measurements were made for comparison. RESULTS: Texture analysis showed significant between-group differences for 2 features-skewness and entropy in the hippocampus, the thalamus, and the amygdala-and the volume analysis revealed no between-group difference. These features were significantly correlated with cognitive performance. CONCLUSION: These results support the assumption that signal alterations associated with Parkinson's disease-related cognitive decline can be captured very early by texture analysis. As these changes appear to reflect clinical phenomena, texture analysis may be a promising marker for helping cognitive phenotyping in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.
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Trastornos del Conocimiento , Disfunción Cognitiva , Enfermedad de Parkinson , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagenRESUMEN
Motor programme for gait initiation can vary as a function of attentional resources. The objective of the present study was to determine whether alertness, orientation and executive control can modulate cortical activation during step initiation. The attention network test (ANT) was used to control the influence of different attentional components on kinetic characteristics of step initiation and the associated cortical activity. Thirty healthy adults performed ANT combined with step initiation. The step execution time (SET) and anticipatory postural adjustments (APAs) were recorded. Movement-related cortical potentials (MRCPs) and event-related spectral perturbations (ERSPs) after response emission were analysed according to the presence or absence of cueing or conflict resolution. Step reaction time and thus SET were significantly shorter with cueing, whereas APA duration and SET were longer during conflict resolution. Moreover, alertness was related to a higher rate of anticipated responses, and conflicting situations were associated with a greater amount of multiple APAs. Attentional load did not affect MRCPs but ERSPs: trials with a cue showed earlier posterior alpha and beta desynchronisations before APA onset. Furthermore, we found earlier, more pronounced and longer alpha- and beta-band desynchronisations over the sensorimotor cortex for trials with incongruent flankers. Our results showed that attention has an impact on step initiation. A specific pattern of response-locked ERSPs seems to mirror behavioural effects of attentional load on step initiation. This new paradigm combining ANT and step initiation is, therefore, promising to investigate the interaction between attention and gait initiation in pathological populations.
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Atención/fisiología , Cognición/fisiología , Marcha/fisiología , Equilibrio Postural/fisiología , Adulto , Potenciales Evocados/fisiología , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Postura/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Cognitive symptoms are common in patients with Parkinson's disease. Characterization of a patient's cognitive profile is an essential step toward the identification of predictors of cognitive worsening. OBJECTIVE: The aim of this study was to investigate the use of the combination of resting-state EEG and data-mining techniques to build characterization models. METHODS: Dense EEG data from 118 patients with Parkinson's disease, classified into 5 different groups according to the severity of their cognitive impairments, were considered. Spectral power analysis within 7 frequency bands was performed on the EEG signals. The obtained quantitative EEG features of 100 patients were mined using 2 machine-learning algorithms to build and train characterization models, namely, support vector machines and k-nearest neighbors models. The models were then blindly tested on data from 18 patients. RESULTS: The overall classification accuracies were 84% and 88% for the support vector machines and k-nearest algorithms, respectively. The worst classifications were observed for patients from groups with small sample sizes, corresponding to patients with the severe cognitive deficits. Whereas for the remaining groups for whom an accurate diagnosis was required to plan the future healthcare, the classification was very accurate. CONCLUSION: These results suggest that EEG features computed from a daily clinical practice exploration modality in-that it is nonexpensive, available anywhere, and requires minimal cooperation from the patient-can be used as a screening method to identify the severity of cognitive impairment in patients with Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society.
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Trastornos del Conocimiento/fisiopatología , Electroencefalografía , Aprendizaje Automático , Enfermedad de Parkinson/fisiopatología , Anciano , Algoritmos , Cognición/fisiología , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Máquina de Vectores de SoporteRESUMEN
Cognitive deficits are common in Parkinson's disease and we suspect that dysfunctions of connected brain regions can be the source of these deficits. The aim of the present study was to investigate changes in whole-brain intrinsic functional connectivity according to differences in cognitive profiles in Parkinson's disease. 119 participants were enrolled and divided into four groups according to their cognitive phenotypes (determined by a cluster analysis): (i) 31 cognitively intact patients (G1), (ii) 31 patients with only slight mental slowing (G2), (iii) 43 patients with mild to moderate deficits mainly in executive functions (G3), (iv) 14 patients with severe deficits in all cognitive domains (G4-5). Rs-fMRI whole-brain connectivity was examined by two complementary approaches: graph theory for studying network functional organization and network-based statistics (NBS) for exploring functional connectivity amongst brain regions. After adjustment for age, duration of formal education and center of acquisition, there were significant group differences for all functional organization indexes: functional organization decreased (G1 > G2 > G3 > G4-5) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, P < 0.01) mainly concerned the ventral prefrontal, parietal, temporal and occipital cortices as well as the basal ganglia. In Parkinson's disease, brain network organization is progressively disrupted as cognitive impairment worsens, with an increasing number of altered connections between brain regions. We observed reduced connectivity in highly associative areas, even in patients with only slight mental slowing. The association of slowed mental processing with loss of connectivity between highly associative areas could be an early marker of cognitive impairment in Parkinson's disease and may contribute to the detection of prodromal forms of Parkinson's disease dementia. Hum Brain Mapp 38:1604-1621, 2017. © 2016 Wiley Periodicals, Inc.
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Mapeo Encefálico , Encéfalo/patología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Vías Nerviosas/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Anciano , Atención/fisiología , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Función Ejecutiva , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oxígeno/sangreRESUMEN
BACKGROUND: Parkinsonian patients have a tendency to speed up during repetitive motor tasks (festination) and to experience sudden motor blocks (freezing). In this article, we prospectively studied the appearance and progression of these phenomena in 30 early-stage PD patients. METHODS: A total of 30 controls and early-stage PD patients were assessed in the "off-drug" condition at baseline and 2 years later. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients also performed diadochokinetic tasks with 3 different effectors (repetitive, antiphase movements for the hands and feet, and repetitive syllable production for the orofacial effector) at frequencies ranging from 1 to 7 Hz (in random order). The primary endpoint was the occurrence of freezing and festination. RESULTS: At baseline, freezing was observed in 6.5% of the trials in PD patients (43% of the patients) and 2.3% of the trials in controls, and festination was observed in 5.7% of the trials in patients (53% of the patients) and 0.8% of the trials in controls. These proportions were slightly higher in patients 2 years later. None of the patients presented freezing of gait at baseline, but 2 displayed this condition 2 years later. These phenomena occurred more frequently for the limb effectors than for the orofacial effector. Freezing and festination were associated with the akinetic-rigid subtype, although tremor-dominant patients displayed greater rhythm variability outside episodes. CONCLUSION: Freezing and festination of the upper and lower limbs are observed soon after the diagnosis of PD and may be early biomarkers for disease progression. © 2016 International Parkinson and Movement Disorder Society.
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Progresión de la Enfermedad , Trastornos Neurológicos de la Marcha/fisiopatología , Actividad Motora/fisiología , Enfermedad de Parkinson/fisiopatología , Anciano , Femenino , Trastornos Neurológicos de la Marcha/etiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Estudios Prospectivos , Temblor/etiología , Temblor/fisiopatologíaRESUMEN
BACKGROUND: The aim of this work was to construct a model for anxiety in PD and compare the relative contributions of PD-specific and -nonspecific general population risk factors for anxiety in this model. METHODS: Structural equation modeling of associations of risk factors with the anxiety outcome using a cross-sectional data set of 342 patients with PD were used. RESULTS: A model with acceptable to good fit was generated that explained 65% of the variance in anxiety scores. A previous history of depression and the severity of the depressive symptoms scored on the Hamilton Depression Rating Scale were the only nonspecific variables with a direct effect on anxiety. The presence of motor fluctuations and disease-related decline in activities of daily living were PD-specific markers of anxiety. Nonspecific risk factors had a greater influence in the model than PD-specific risk factors. Standardized regression coefficients suggested that the Hamilton Depression Rating Scale score was the most important contributor to the variation in anxiety. A post-hoc analysis showed that the effects of the following variables on anxiety levels were fully mediated by depression: sex; family history of depression; previous history of anxiety; cognitive status; difficulties in non-disease-specific activities of daily living; and severity of motor signs. CONCLUSION: In this cross-sectional study, we showed that nonspecific general population risk factors are more important markers for anxiety than PD-specific risk factors. Depression was the most prominent marker. PD-specific markers for anxiety appear to be more situational and related to off periods and disease-specific disturbances of activities of daily living.
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Actividades Cotidianas/psicología , Trastornos de Ansiedad/psicología , Ansiedad/psicología , Depresión/psicología , Trastorno Depresivo/psicología , Enfermedad de Parkinson/psicología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores de RiesgoRESUMEN
Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). These adjustments create the propulsive forces required to reach the steady-state gait at the end of the first step and can be studied by the displacement of the centre of pressure. The objective of this study was to demonstrate that APAs can be modulated by visuospatial attentional processes prior to motor execution. An adaptation of the Posner paradigm was used to assess attention during step initiation. Twelve healthy subjects performed a gait initiation task under three conditions: a no-cue condition (the control experiment), a double-cue condition (alerting attention) and a single-cue condition (orienting attention). The kinetic and kinematic parameters of the APAs and step initiation were recorded. The time to step initiation was significantly shorter in the alerting condition than in the control condition. This effect was associated with the earlier occurrence of APAs. Orienting condition also had an effect and was associated with the modulation of APA errors (defined as a contralateral shift of the CoP on the cue side before corrective shifting to the target side). Behavioural measurements (such as postural preparation of step initiation) may reflect the interaction between attention and locomotion. Our results show that the different components of attention each have a specific influence on step initiation parameters.
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Atención/fisiología , Marcha/fisiología , Equilibrio Postural/fisiología , Percepción Espacial/fisiología , Adulto , Fenómenos Biomecánicos , Señales (Psicología) , Electromiografía , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Anciano , Catecol O-Metiltransferasa , Dopamina/metabolismo , Método Doble Ciego , Genotipo , Humanos , Levodopa/uso terapéutico , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test-retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C.
Asunto(s)
Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/etiología , Enfermedad de Parkinson/complicaciones , Escalas de Valoración Psiquiátrica , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Psicometría/métodos , Análisis de Regresión , Índice de Severidad de la EnfermedadRESUMEN
The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n=260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ=0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ=0.56); apathy with the Lille Apathy Rating Scale (ρ=0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia.