RESUMEN
Experimental, neuropathological and cerebrospinal fluid (CSF) studies support τ and amyloid-ß (Aß) relevance in Parkinson's disease (PD) related dementia. Lesser motor fluctuations (MFs) and non-motor features have also been related to PD-dementia. Yet, little is known about the association of MFs and non-motor symptoms with CSF τ and Aß in PD. We hypothesized that lesser MFs and non-motor predominance are related to these CSF markers and dementia-risk in PD. We studied 58 PD patients (dementia at baseline, n=21; dementia at 18-months, n=35) in whom CSF Aß and τ had been determined with ELISA techniques. MFs and a number of non-motor symptoms (apathy, anxiety, irritability, depression, visual hallucinations, spatial disorientation, memory complaints) over disease course were dichotomized as absent-mild vs. moderate-severe by retrospective clinical chart review blind to CSF findings. Non-motor predominance was defined as ≥3 non-motor symptoms (after the cohort-median of non-motor symptoms per patient) with ≥2 being moderate-severe and ≥1 having been present from onset, with all these being more disabling overall than motor features. Cross-sectionally, CSF biomarkers were non-parametrically compared according to dichotomized MFs and non-motor predominance. Longitudinally, dementia was the outcome (dependent variable), CSF markers, MFs and non-motor predominance were the predictors (independent variables), and potential modifiers as age, sex, and memory complaints were the covariates in binary regression models. Absent-mild MFs were associated with higher CSF τ markers and shorter time-to-dementia, while non-motor predominance and decreasing CSF Aß independently increased longitudinal dementia-risk. In summary, absent-mild MFs, non-motor predominance and CSF τ and Aß might define endophenotypes related to the timing or risk of dementia in PD.
Asunto(s)
Péptidos beta-Amiloides/líquido cefalorraquídeo , Demencia/líquido cefalorraquídeo , Actividad Motora , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Parkinson/psicología , Proteínas tau/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Estudios Transversales , Demencia/epidemiología , Demencia/etiología , Endofenotipos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Análisis de Regresión , Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Factores de TiempoAsunto(s)
Apatía , Enfermedades de los Ganglios Basales/complicaciones , Neoplasias Encefálicas/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Enfermedad de Parkinson Secundaria/etiología , Anciano , Enfermedad Cerebrovascular de los Ganglios Basales/complicaciones , Enfermedad Cerebrovascular de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Diagnóstico Diferencial , Progresión de la Enfermedad , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson Secundaria/diagnóstico , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Enfermedad de Parkinson Secundaria/metabolismoAsunto(s)
Dopaminérgicos/efectos adversos , Distonía/etiología , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Levodopa/efectos adversos , Parálisis Supranuclear Progresiva/tratamiento farmacológico , Anciano , Diagnóstico Diferencial , Dopaminérgicos/uso terapéutico , Distonía/diagnóstico , Distonía/terapia , Femenino , Trastornos Neurológicos de la Marcha/diagnóstico , Humanos , Levodopa/uso terapéutico , Parálisis Supranuclear Progresiva/diagnósticoRESUMEN
BACKGROUND: Patients with cervical dystonia (CD) present with an impaired performance of voluntary neck movements, which are usually slow and limited. We hypothesized that such abnormality could involve defective preparation for task execution. Therefore, we examined motor preparation in CD patients using the StartReact method. In this test, a startling auditory stimulus (SAS) is delivered unexpectedly at the time of the imperative signal (IS) in a reaction time task to cause a faster execution of the prepared motor programme. We expected that CD patients would show an abnormal StartReact phenomenon. METHODS: Fifteen CD patients and 15 age matched control subjects (CS) were asked to perform a rotational movement (RM) to either side as quick as possible immediately after IS perception (a low intensity electrical stimulus to the II finger). In randomly interspersed test trials (25%) a 130 dB SAS was delivered simultaneously with the IS. We recorded RMs in the horizontal plane with a high speed video camera (2.38 ms per frame) in synchronization with the IS. The RM kinematic-parameters (latency, velocity, duration and amplitude) were analyzed using video-editing software and screen protractor. Patients were asked to rate the difficulty of their RMs in a numerical rating scale. RESULTS: In control trials, CD patients executed slower RMs (repeated measures ANOVA, p<0.10(-5)), and reached a smaller final head position angle relative to the midline (p<0.05), than CS. In test trials, SAS improved all RMs in both groups (p<0.10(-14)). In addition, patients were more likely to reach beyond their baseline RM than CS (χ(2), p<0.001) and rated their performance better than in control trials (t-test, p<0.01). CONCLUSION: We found improvement of kinematic parameters and subjective perception of motor performance in CD patients with StartReact testing. Our results suggest that CD patients reach an adequate level of motor preparation before task execution.