Protective Activity of Erythropoyetine in the Cognition of Patients with Parkinson's Disease.

Introduction: Treatment strategies in Parkinson's disease (PD) can improve a patient's quality of life but cannot stop the progression of PD. We are looking for different alternatives that modify the natural course of the disease and recent research has demonstrated the neuroprotective properties of erythropoietin. In Cuba, the Center for Molecular Immunology (CIM) is a cutting edge scientific center where the recombinant form (EPOrh) and recombinant human erythropoietin with low sialic acid (NeuroEPO) are produced. We performed two clinical trials to evaluate the safety and tolerability of these two drugs in PD patients. In this paper we want to show the positive results of the additional cognitive tests employed, as part of the comprehensive assessment. Materials and method: Two studies were conducted in PD patients from the outpatient clinic of CIREN, including n = 10 and n = 26 patients between 60 and 66 years of age, in stages 1 to 2 of the Hoehn and Yahr Scale. The first study employed recombinant human (rhEPO) and the second an intranasal formulation of neuroEPO. All patients were evaluated with a battery of neuropsychological scales composed to evaluate global cognitive functioning, executive function, and memory. Results: The general results in both studies showed a positive response to the cognitive functions in PD patients, who were undergoing pharmacological treatment with respect to the evaluation (p < 0.05) before the intervention. Conclusions: Erythropoietin has a discrete positive effect on the cognitive functions of patients with Parkinson's disease, which could be interpreted as an effect of the neuroprotective properties of this molecules. To confirm the results another clinical trial phase III with neuroEPO is in progress, also designed to discard any influence of a placebo effect on cognition.

Unilateral subthalamotomy in Parkinson's disease: Cognitive, psychiatric and neuroimaging changes.

Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency.

Effectiveness of a Computer-Based Training Program of Attention and Memory in Patients with Acquired Brain Damage.

Many training programs have been designed using modern software to restore the impaired cognitive functions in patients with acquired brain damage (ABD). The objective of this study was to evaluate the effectiveness of a computer-based training program of attention and memory in patients with ABD, using a two-armed parallel group design, where the experimental group (n = 50) received cognitive stimulation using RehaCom software, and the control group (n = 30) received the standard cognitive stimulation (non-computerized) for eight weeks. In order to assess the possible cognitive changes after the treatment, a post-pre experimental design was employed using the following neuropsychological tests: Wechsler Memory Scale (WMS) and Trail Making test A and B. The effectiveness of the training procedure was statistically significant (p < 0.05) when it established the comparison between the performance in these scales, before and after the training period, in each patient and between the two groups. The training group had statistically significant (p < 0.001) changes in focused attention (Trail A), two subtests (digit span and logical memory), and the overall score of WMS. Finally, we discuss the advantages of computerized training rehabilitation and further directions of this line of work.

Clinical impact of RehaCom software for cognitive rehabilitation of patients with acquired brain injury.

We describe the clinical impact of the RehaCom computerized cognitive training program instituted in the International Neurological Restoration Center for rehabilitation of brain injury patients. Fifty patients admitted from 2008 through 2010 were trained over 60 sessions. Attention and memory functions were assessed with a pre- and post-treatment design, using the Mini-Mental State Examination, Wechsler Memory Scale and Trail Making Test (Parts A and B). Negative effects were assessed, including mental fatigue, headache and eye irritation. The program's clinical usefulness was confirmed, with 100% of patients showing improved performance in trained functions.

Correlación entre el examen mínimo del estado mental y la escala de memoria de Wechsler en una muestra de pacientes con daño cerebral / Correlation between mini mental state examination and the Wechsler memory scale in a sample of patients with sequel

Introducción. La afectación de los procesos cognitivos es muy frecuente en pacientes con daño cerebral adquirido (DCA). Una adecuada evaluación neuropsicológica permite arribar a un diagnóstico certero de la magnitud del déficit y su repercusión funcional. Este estudio examina la correlación entre un test de cribado tradicional, el Examen Mínimo del Estado Mental (MMSE) y un test específico para la evaluación de la memoria, la Escala de Memoria de David Wechsler-I (WMS-I), en una muestra de 124 pacientes con DCA. Para ello se empleó el Método de Pearson. La correlación global obtenida entre ambos test fue significativa (p≤0.05) Conclusiones. Los test de cribado constituyen una manera breve y práctica para aproximarnos al diagnóstico neuropsicológico y este estudio de correlación constata la sensibilidad y el valor predictivo del MMSE como uno de los test de rastreo más empleados en la práctica clínica para orientar la exploración de las funciones comprometidas tras la lesión cerebral. No obstante, consideramos que en modo alguno deberían sustituirse las pruebas neuropsicológicas por los test de cribado para evaluar cognición en pacientes con daño cerebral adquirido.

Introduction. The cognitive impairments are frequently in patients with acquired brain injury (ABI). The neuropsychological assessment must provide a good diagnosis of the severity and functional repercussion of the cognitive impairments. This study examines the correlation between a traditional screening test, Mini–Mental State Examination (MMSE) and a specific test for the memory evaluation, the Wechsler Memory Scale I (WMS)I, in a sample of 124 patients with sequel of ABI. The global correlation (using coefficient of Pearson) between MMSE and WMS I was statistical significant (p≤0.05). Conclusions. The screening test constitutes an easy and brief way to obtain an adequate neuropsychological diagnosis. This correlation verifies the sensibility and the predictor value of the MMSE like one of the most employees test in the clinical practice to guide the exploration by damaged functions after the brain injury. Nevertheless, we consider that neuropsychological assessment in acquired brain injury patients should not be substituted by a scrutiny instrument.

Semantic and phonemic verbal fluency in Parkinson's disease: Influence of clinical and demographic variables.

Changes of cognitive function in PD have been extensively documented and defined as a 'frontal' type executive dysfunction. One of the main components of this executive dysfunction is the impairment of verbal fluency. The aim of the present study was to assess semantic and phonemic fluency in a large sample of PD patients and to investigate the effect of clinical and sociodemographic variables on verbal fluency in this patient group. Three hundred patients with idiopathic Parkinson's disease who were consecutive referrals to our clinic and 50 age and education matched healthy controls completed the phonemic and semantic verbal fluency tasks. Both phonemic and semantic verbal fluency were significantly impaired in PD patients relative to matched controls. Stage of illness, presence of depression, education and age influenced verbal fluency measures. Regression analyses established that global measures of cognitive ability (MMSE) and executive function (FAB) and side of onset of motor symptoms predicted 36-37% of variance of phonemic or semantic verbal fluency measures. Thus, future studies aimed at assessing cognitive functioning in PD patients treated by deep brain stimulation (DBS) should adequately take into account several factors (stage of illness, depression, executive functioning) which may potentially influence performance on verbal fluency tasks.

Use of Cuban recombinant human erythropoietin in Parkinson's disease treatment.

INTRODUCTION: Recombinant human erythropoietin is used primarily to treat anemia. There is evidence of its neuroprotective capacity from preclinical studies in Parkinson's disease and other neurodegenerative diseases. Recombinant human erythropoietin produced in Cuba (ior-EPOCIM) is registered and approved for use in humans in Cuba and in a number of other countries. OBJECTIVE: Assess safety and possible neuroprotective effect of ior-EPOCIM in a group of Parkinson's disease patients. METHODS: A three-phase exploratory study (proof of concept) was conducted from August 2008 to April 2009: preliminary assessment, treatment (weeks 1-5), and post-treatment (weeks 6-35). Participants were 10 Parkinson's disease patients (8 men, 2 women) from the outpatient clinic at the International Neurological Restoration Center, all at least one year post onset, aged 47-65 years. The ior-EPOCIM was administered subcutaneously in a once-weekly dose (60 IU/kg body weight) for five weeks. Therapy with patients' antiparkinsonian drugs was maintained throughout the study, except during motor examination, conducted following a 12-hour withdrawal (OFF condition). Safety was evaluated primarily by recording adverse events (by intensity and causality) from start of treatment until the study's completion. Hematological parameters and blood pressure were also measured because of their direct relationship to the medication's action. To evaluate possible neuroprotective activity, variables were included related to patients' motor function and cognitive and affective status, measured using internationally recognized scales. All variables were evaluated before, during and after treatment. Data were processed using a fixed-effects linear model, with a repeated-measures design (significance level p ≤ 0.05). RESULTS: Three patients experienced mild adverse events (precordial discomfort and hypertension in one; leg fatigue in another; renal colic in a third), with a possible causal relationship in the first two that was neither life threatening nor required hospitalization. Hemoglobin was the only hematological parameter that showed a growing and significant increase (p < 0.001), but without reaching pathological levels. The other variables presented clinically positive and statistically significant changes compared to pretreatment assessment: motor function (p < 0.001), cognitive status (p < 0.001) and mood (p = 0.013). CONCLUSIONS At the dosage used, ior-EPOCIM was safe and well tolerated in these Parkinson's disease patients. Further studies are needed to corroborate these results and evaluate the medication's possible neuroprotective effect. KEYWORDS Parkinson disease, erythropoietin, recombinant proteins, neuroprotective agents, clinical trial, safety, ior-EPOCIM, Cuba.

Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson's disease.

Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.

Event related potentials to the subject's own face

When subjects are able to recognize facial stimulus, ERPs display a tendency for an increased positivity in response to Familiar Faces (FF) and increased negativity in response to Unfamiliar Faces (UF). These changes seem to depend upon the experimental manipulation of the psychological variables (timing of face presentation in order to access either early or late subcomponents associated with face recognition). Characteristic of the aforementioned studies: faces presnt only two degrees of familiarity (UF vs. FF); a given face is presented for a limited number of times; previous studies used as FF famous people which the Ss only knew via the mass media. To our knowledge the faces of relatives or friends have not been used as stimuli. As an extreme case, the subject's own face is a highly familiar stimulus to each subject. ERP amplitude should reflect this effect with an enhanced positivity(AU)

Event related potentials to the subject's own face

When subjects are able to recognize facial stimulus, ERPs display a tendency for an increased positivity in response to Familiar Faces (FF) and increased negativity in response to Unfamiliar Faces (UF). These changes seem to depend upon the experimental manipulation of the psychological variables (timing of face presentation in order to access either early or late subcomponents associated with face recognition). Characteristic of the aforementioned studies: faces presnt only two degrees of familiarity (UF vs. FF); a given face is presented for a limited number of times; previous studies used as FF famous people which the Ss only knew via the mass media. To our knowledge the faces of relatives or friends have not been used as stimuli. As an extreme case, the subject's own face is a highly familiar stimulus to each subject. ERP amplitude should reflect this effect with an enhanced positivity(AU)

Event related potentials to the subject's own face

When subjects are able to recognize facial stimulus, ERPs display a tendency for an increased positivity in response to Familiar Faces (FF) and increased negativity in response to Unfamiliar Faces (UF). These changes seem to depend upon the experimental manipulation of the psychological variables (timing of face presentation in order to access either early or late subcomponents associated with face recognition). Characteristic of the aforementioned studies: faces presnt only two degrees of familiarity (UF vs. FF); a given face is presented for a limited number of times; previous studies used as FF famous people which the Ss only knew via the mass media. To our knowledge the faces of relatives or friends have not been used as stimuli. As an extreme case, the subject's own face is a highly familiar stimulus to each subject. ERP amplitude should reflect this effect with an enhanced positivity (AU)

Event related potentials to the subject's own face

When subjects are able to recognize facial stimulus, ERPs display a tendency for an increased positivity in response to Familiar Faces (FF) and increased negativity in response to Unfamiliar Faces (UF). These changes seem to depend upon the experimental manipulation of the psychological variables (timing of face presentation in order to access either early or late subcomponents associated with face recognition). Characteristic of the aforementioned studies: faces presnt only two degrees of familiarity (UF vs. FF); a given face is presented for a limited number of times; previous studies used as FF famous people which the Ss only knew via the mass media. To our knowledge the faces of relatives or friends have not been used as stimuli. As an extreme case, the subject's own face is a highly familiar stimulus to each subject. ERP amplitude should reflect this effect with an enhanced positivity