Hybrid time-dependent Ginzburg-Landau simulations of block copolymer nanocomposites: nanoparticle anisotropy

Block copolymer melts are perfect candidates to template the position of colloidal nanoparticles in the nanoscale, on top of their well-known suitability for lithography applications. This is due to their ability to self-assemble into periodic ordered structures, in which nanoparticles can segregate depending on the polymer-particle interactions, size and shape. The resulting coassembled structure can be highly ordered as a combination of both the polymeric and colloidal properties. The time-dependent Ginzburg-Landau model for the block copolymer was combined with Brownian dynamics for nanoparticles, resulting in an efficient mesoscopic model to study the complex behaviour of block copolymer nanocomposites. This review covers recent developments of the time-dependent Ginzburg-Landau/Brownian dynamics scheme. This includes efforts to parallelise the numerical scheme and applications of the model. The validity of the model is studied by comparing simulation and experimental results for isotropic nanoparticles. Extensions to simulate nonspherical and inhomogeneous nanoparticles are discussed and simulation results are discussed. The time-dependent Ginzburg-Landau/Brownian dynamics scheme is shown to be a flexible method which can account for the relatively large system sizes required to study block copolymer nanocomposite systems, while being easily extensible to simulate nonspherical nanoparticles

Measuring the functional impact of cognitive impairment in Huntington's disease

Acord transformatiu CRUE-CSICBackground: Patients with Huntington's disease (HD) exhibit a variable predominance of cognitive, behavioral and motor symptoms. A specific instrument focusing on the impact of cognitive impairment in HD over functional capacity is lacking. Objective: To address the need for a brief and specifically developed HD questionnaire able to capture functional aspects suspected to be sensitive to cognitive impairment. Methods: We developed and validated the "Huntington's Disease-Cognitive Functional Rating Scale" (HD-CFRS) in 78 symptomatic carriers of the Huntington's disease mutation. We also administered the HD-CFRS to a knowledgeable informant to measure the level of agreement. To explore the association between HD-CFRS scores and participants' cognitive status, we administered objective measures of cognition. Participants were classified as cognitively preserved (HD-NC), as having mild cognitive impairment (HD-MCI), or as having dementia (HD-Dem). Results: The HD-CFRS showed concurrent validity and internal consistency in the three groups. HD carriers and informants in the HD-NC group obtained similar HD-CFRS scores. However, in patients with mild cognitive impairment and dementia, informers reported greater functional impairment than HD participants. The HD-CFRS total score showed strong correlations with measures assessing cognition. Conclusions: These findings support the utility of the HD-CFRS as a brief and reliable instrument to measure functional defects associated with cognitive impairment in HD. We believe this questionnaire could be a useful tool both for clinical practice and research

The impact of dopaminergic treatment over cognitive networks in Parkinson's disease : Stemming the tide?

Altres ajuts: Fundació la Marató de TV3/20142910Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age-matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow-up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default-mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN-DMN connectivity characterized the participants in the ON state, while within-DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN-DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN-DM hyperconnectivity

The impact of dopaminergic treatment over cognitive networks in Parkinson's disease: Stemming the tide?

Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age-matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow-up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default-mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN-DMN connectivity characterized the participants in the ON state, while within-DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN-DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN-DM hyperconnectivity

Predicting Impulse Control Disorders in Parkinson Disease through Incentive Biomarkers

Altres ajuts: Fundació la Marató de TV3 (2014/U/477, 20142910); Fondo Europeo de Desarrollo Regional (FEDER); Pla Estratègic de Recerca i Innovació (SLT008/18); CERCA (CEntres de Recerca de Catalunya); CIBERNED (Centro de Investigación Biomédica en Red de enfermedades NEuroDegenerativas).Objective: This study was undertaken to evaluate whether the feedback-related negativity (FRN)-a neurophysiological marker of incentive processing-can be used to predict the development of impulse control disorders (ICDs) in Parkinson disease (PD). Methods: The longitudinal cohort consisted of consecutive nondemented PD patients with no ICD history. We recorded FRN signals while they performed a gambling task. We calculated the mean amplitude difference between losses and gains (FRNdiff) to be used as a predictor of future ICD development. We performed prospective biannual follow-up assessments for 30 months to detect incident ICDs. Finally, we evaluated how basal FRNdiff was associated with posterior development of ICDs using survival models. Results: Between October 7, 2015 and December 16, 2016, we screened 120 patients. Among them, 94 patients performed the gambling and 92 completed the follow-up. Eighteen patients developed ICDs during follow-up, whereas 74 remained free of ICDs. Baseline FRNdiff was greater in patients who developed ICDs than in those who did not (−2.33μV vs −0.84μV, p = 0.001). No other significant baseline differences were found. The FRNdiff was significantly associated with ICD development in the survival models both when not adjusted (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.58-0.91, p = 0.006) and when controlling for dopamine replacement therapy, sex, and age (HR = 0.74, 95% CI = 0.55-0.97, p = 0.035). None of the impulsivity measures evaluated was related to ICD development. Interpretation: Reward-processing differences measured by FRN signals precede ICD development in PD. This neurophysiological marker permits identification of patients with high risk of ICD development. ANN NEUROL 2022;92:974-984

Neural signatures of predictive language processing in Parkinson's disease with and without mild cognitive impairment

Altres ajuts: Fundació la Marató de TV3 (2014/U/477, 20142910)Cognitive deficits are common in Parkinson's disease (PD), with some PD patients meeting criteria for mild cognitive impairment (MCI). An unaddressed question is whether linguistic prediction is preserved in PD. This ability is nowadays deemed crucial for achieving fast and efficient comprehension, and it may be negatively impacted by cognitive deterioration in PD. To fill this gap of knowledge, we used event-related potentials (ERPs) to evaluate mechanisms of linguistic prediction in a sample of PD patients (on dopamine compensation) with and without MCI. To this end, participants read sentence contexts that were predictive or not about a sentence-final word. The final word appeared after one sec, matching or mismatching the prediction. The introduction of the interval allowed to capture neural responses both before and after sentence-final words, reflecting semantic anticipation and semantic processing. PD patients with normal cognition (N = 58) showed ERP responses comparable to those of matched controls. Specifically, in predictive contexts, a slow negative potential developed prior to sentence-final words, reflecting semantic anticipation. Later, expected words elicited reduced N400 responses (compared to unexpected words), indicating facilitated semantic processing. PD patients with MCI (N = 20) showed, in addition, a prolongation of the N400 congruency effect (compared to matched PD patients without MCI), indicating that further cognitive decline impacts semantic processing. Finally, lower verbal fluency scores correlated with prolonged N400 congruency effects and with reduced pre-word differences in all PD patients (N = 78). This relevantly points to a role of deficits in temporal-dependent mechanisms in PD, besides prototypical frontal dysfunction, in altered semantic anticipation and semantic processing during sentence comprehension

A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease

Altres ajuts: CERCA; CIBERNED; La Marató de TV3 (2014/U/477, 20142910); Fondo Europeo de Desarrollo Regional (FEDER).Background: Apathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence. Objective: We studied the effects of safinamide on apathy in PD. Methods: Prospective, 24-week, two-site, randomized, double-blind, placebo-controlled, parallel-group exploratory study in non-demented PD on stable dopaminergic therapy randomized 1:1 to adjunct safinamide (50 mg/day for 2 weeks and 100 mg/day for 22 weeks) or placebo. The primary endpoint was the mean change from baseline to week 24 on the Apathy Scale (AS) total score. Secondary endpoints included changes in cognition, activities of daily living, motor scores, the impression of change, and safety and tolerability measures. Results: In total, 30 participants (active treatment = 15; placebo = 15; 80% showing clinically significant apathetic symptoms according to the AS) were enrolled, and included in the intention-to-treat analysis. Change in AS (ANOVA) showed a trend to significance [p = 0.059] mediated by a more marked decrease in AS score with safinamide (−7.5 ± 6.9) than with placebo (−2.8 ± 5.7). Post-hoc analysis (paired t-test) showed a significant positive change in the AS score between 12-week and 24-week [p = 0.001] only in the active group. No significant or trend changes were found for any of the secondary outcome variables. Adverse events were few and only mild in both treatment groups. Conclusions: Safinamide was safe and well-tolerated, but failed to provide evidence of improved apathy. The positive trend observed in the post-hoc analyses deserves to be studied in depth in larger studies. Trial Registration: EudraCT 2017-003254-17

Pattern of Regional Cortical Thinning Associated with Cognitive Deterioration in Parkinson's Disease

Altres ajuts: Sociedad Española de Radiologia Médica (SERAM 06-09)Background: Dementia is a frequent and devastating complication in Parkinson's disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients. Objectives and Methods: We aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer. Results: In a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex. Conclusions: The pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing

Present and future of parkinson’s disease in Spain: Parkinson-2030 delphi project

Parkinson’s disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000–150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients’ and caregivers’ lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD.This project was funded by Zambon S.A.U

Present and Future of Parkinson’s Disease in Spain: PARKINSON-2030 Delphi Project

Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients' and caregivers' lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD