Beyond shallow feelings of complex affect: Non-motor correlates of subjective emotional experience in Parkinson's disease.

Affective disorders in Parkinson's disease (PD) concern several components of emotion. However, research on subjective feeling in PD is scarce and has produced overall varying results. Therefore, in this study, we aimed to evaluate the subjective emotional experience and its relationship with autonomic symptoms and other non-motor features in PD patients. We used a battery of film excerpts to elicit Amusement, Anger, Disgust, Fear, Sadness, Tenderness, and Neutral State, in 28 PD patients and 17 healthy controls. Self-report scores of emotion category, intensity, and valence were analyzed. In the PD group, we explored the association between emotional self-reported scores and clinical scales assessing autonomic dysregulation, depression, REM sleep behavior disorder, and cognitive impairment. Patient clustering was assessed by considering relevant associations. Tenderness occurrence and intensity of Tenderness and Amusement were reduced in the PD patients. Tenderness occurrence was mainly associated with the overall cognitive status and the prevalence of gastrointestinal symptoms. In contrast, the intensity and valence reported for the experience of Amusement correlated with the prevalence of urinary symptoms. We identified five patient clusters, which differed significantly in their profile of non-motor symptoms and subjective feeling. Our findings further suggest the possible existence of a PD phenotype with more significant changes in subjective emotional experience. We concluded that the subjective experience of complex emotions is impaired in PD. Non-motor feature grouping suggests the existence of disease phenotypes profiled according to specific deficits in subjective emotional experience, with potential clinical implications for the adoption of precision medicine in PD. Further research on larger sample sizes, combining subjective and physiological measures of emotion with additional clinical features, is needed to extend our findings.

The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity.

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson's disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG.

EEG-Derived Functional Connectivity Patterns Associated with Mild Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: To evaluate EEG-derived functional connectivity (FC) patterns associated with mild cognitive impairment (MCI) in Parkinson's disease (PD). METHODS: A sample of 15 patients without cognitive impairment (PD-WCI), 15 with MCI (PD-MCI), and 26 healthy subjects were studied. The EEG was performed in the waking functional state with eyes closed, for the functional analysis it was used the synchronization likelihood (SL) and graph theory (GT). RESULTS: PD-MCI patients showed decreased FC in frequencies alpha, in posterior regions, and delta with a generalized distribution. Patients, compared to the healthy people, presented a decrease in segregation (lower clustering coefficient in alpha p = 0.003 in PD-MCI patients) and increased integration (shorter mean path length in delta (p = 0.004) and theta (p = 0.002) in PD-MCI patients). There were no significant differences in the network topology between the parkinsonian groups. In PD-MCI patients, executive dysfunction correlated positively with global connectivity in beta (r = 0.47) and negatively with the mean path length at beta (r = -0.45); alterations in working memory were negatively correlated with the mean path length at beta r = -0.45. CONCLUSIONS: PD patients present alterations in the FC in all frequencies, those with MCI show less connectivity in the alpha and delta frequencies. The neural networks of the patients show a random topology, with a similar organization between patients with and without MCI. In PD-MCI patients, alterations in executive function and working memory are related to beta integration.

Short-term Tolerance of Nasally-administered NeuroEPO in Patients with Parkinson Disease.

INTRODUCTION: No neuroprotective treatment has been able to successfully halt the progression of Parkinson disease or prevent development of associated complications. Recombinant erythropoetin (EPO), an erythropoiesis-stimulating agent originally indicated in anemia, produced and manufactured in Cuba (iorEPOCIM, CIMAB S.A, Havana, Cuba) has neuroprotective properties. NeuroEPO is a new nasal formulation of recombinant EPO with a low content of sialic acid and without hematopoietic effects. It has neuroprotective effects in animal models. OBJECTIVE: Evaluate short-term tolerance of intranasal NeuroEPO in patients with Parkinson disease. METHODS: As part of a monocentric randomized placebo-controlled double-blind study (registered at www.clinicaltrials.gov number NCT04110678), 26 patients with Parkinson disease (stages 1 and 2 on Hoehn & Yahr Scale), were randomly divided into two groups: NeuroEPO (n = 15) and placebo (n = 11), both treated intranasally either with the drug (1 mL, at a concentration of 1 mg/mL of NeuroEPO) or placebo once a week for 5 weeks. At each application, we recorded any adverse events and blood pressure. To assess potential hematopoietic effects of the drug, hematological and biochemical variables were evaluated one week before and one week after the intervention. RESULTS: There were no significant differences (p = 0.22) between the two groups in terms of frequency of adverse events (20.0% in NeuroEPO and 9.1% in placebo groups). Three patients in NeuroEPO presented nausea, and one vomited (possibly due to the patient's positioning during drug application). One patient in placebo group reported polyuria and nasal irritation. In both groups, the adverse events were mild, brief, required no treatment and did not present sequelae. CONCLUSIONS: Nasally administered NeuroEPO for five weeks in patients with Parkinson disease stages 1 and 2 on Hoehn & Yahr Scale is well tolerated.

Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson's Patients.

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson's Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs.

Satisfaction with Life Scale (SLS-6): First validation study in Parkinson's disease population.

INTRODUCTION: To explore the psychometric attributes of a new Satisfaction with Life Scale (SLS-6) in a wide Spanish-speaking population with Parkinson's disease (PD). METHODS: This was an international, cross-sectional study. Several rater-based and patient-reported outcomes measures for evaluation of PD (e.g., Scales for Outcomes in Parkinson's Disease-Motor) and other constructs (e.g., Duke-UNC Functional Social Support Questionnaire, Scale for Living with Chronic Illness) were applied together with the SLS-6. Acceptability, scaling assumptions, reliability, precision, and construct validity were tested. RESULTS: The study included 324 patients from five countries, with age (mean ± standard deviation) 66.67 ± 10.68 years. None of the SLS-6 items had missing values and all acceptability parameters fulfilled the standard criteria. Scaling assumptions allowed the calculation of a summary index from items 2 to 6, complementary to the global evaluation (item 1). For these five items, Cronbach's alpha was 0.85; the corrected item-total correlation 0.53-0.73; inter-item correlation, 0.45-0.70, with an item homogeneity index of 0.55. The standard error of measurement, based on Cronbach's alpha for a single observation, was 3.48. SLS-6 correlations were moderate to strong (rs ≥ 0.35) with the patient-reported outcomes and weak to moderate with the rater-based assessments used in the study. The SLS-6 total score was significantly different according to PD severity levels established according to Hoehn and Yahr staging, Clinical Impression of Severity Index, and Patient-Based Global Impression of Severity scale. CONCLUSION: The results suggest that SLS-6 is an easy, feasible, acceptable, consistent, precise and valid measure to evaluate satisfaction with life in PD patients.

Abordaje integral en el tratamiento de la enfermedad de Parkinson / Integral approach in Parkinson disease treatment

La Enfermedad de Parkinson Idiopática(EPI) es una afección crónica no trasmisible del Sistema Nervioso Central, de causa degenerativa. La EPI es una de las enfermedades crónicas con mas impacto obre la forma de vida del paciente, pues despúes de su diagnóstico, la mayoría de los casos sobreviven muchos años. Como un tratamiento causal aún no es posible, el objetivo médico es elevar la calidad de vida y lograr el máximo de independencia. Esta es la razón por la que, actualmente la atención se dirige cada vez más hacia un tratamiento multidisciplinario de la enfermedad. El impacto para el individuo y sus familiares frente a este diagnóstico es importante, pues se trata de una enfermedad sin cura, progresiva y con un futuro impredecible. Por tanto, una buena relación médico paciente, además de un adecuado nivel de información, son imprescindibles para su oportuno manejo

Abordaje integral en el tratamiento de la enfermedad de Parkinson / Integral approach in Parkinson disease treatment

La Enfermedad de Parkinson Idiopática(EPI) es una afección crónica no trasmisible del Sistema Nervioso Central, de causa degenerativa. La EPI es una de las enfermedades crónicas con mas impacto obre la forma de vida del paciente, pues despúes de su diagnóstico, la mayoría de los casos sobreviven muchos años. Como un tratamiento causal aún no es posible, el objetivo médico es elevar la calidad de vida y lograr el máximo de independencia. Esta es la razón por la que, actualmente la atención se dirige cada vez más hacia un tratamiento multidisciplinario de la enfermedad. El impacto para el individuo y sus familiares frente a este diagnóstico es importante, pues se trata de una enfermedad sin cura, progresiva y con un futuro impredecible. Por tanto, una buena relación médico paciente, además de un adecuado nivel de información, son imprescindibles para su oportuno manejo(AU)

El factor de activación plaquetaria y su relación con el daño oxidativo / Platelet-activating factor and its relation with the oxidative damage

El factor de activación plaquetaria es un fosfolípido de síntesis endógena relacionado directamente con diversos procesos como isquemia, necrosis, trombosis y otros. El principal blanco de sus efectos deletéreos se encuentra en las células endoteliales, leucocitos y plaquetas, donde provoca graves perturbaciones mecánicas, reológicas y bioquímicas en la unidad circulatoria. Se realizó una revisión bibliográfica del factor de activación plaquetaria, su síntesis endógena, sus funciones biológicas, con especial énfasis en su relación con el daño oxidativo, así como los principales antagonistas conocidos. Se enfatizó el efecto de los ginkgólidos contenidos en el EGB 761 (extracto de Ginkgo biloba) y su aplicación en la clínica de diversos procesos patológicos relacionados con la circulación cerebral y periférica

El factor de activación plaquetaria y su relación con el daño oxidativo / Platelet-activating factor and its relation with the oxidative damage

El factor de activación plaquetaria es un fosfolípido de síntesis endógena relacionado directamente con diversos procesos como isquemia, necrosis, trombosis y otros. El principal blanco de sus efectos deletéreos se encuentra en las células endoteliales, leucocitos y plaquetas, donde provoca graves perturbaciones mecánicas, reológicas y bioquímicas en la unidad circulatoria. Se realizó una revisión bibliográfica del factor de activación plaquetaria, su síntesis endógena, sus funciones biológicas, con especial énfasis en su relación con el daño oxidativo, así como los principales antagonistas conocidos. Se enfatizó el efecto de los ginkgólidos contenidos en el EGB 761 (extracto de Ginkgo biloba) y su aplicación en la clínica de diversos procesos patológicos relacionados con la circulación cerebral y periférica(AU)