Functional alterations in resting-state networks for Theory of Mind in Parkinson's disease.

In Parkinson's disease (PD), impairment of Theory of Mind (ToM) has recently attracted an increasing number of neuroscientific investigations. If and how functional connectivity of the ToM network is altered in PD is still an open question. First, we explored whether ToM network connectivity shows potential PD-specific functional alterations when compared to healthy controls (HC). Second, we tested the role of the duration of PD in the evolution of functional alterations in the ToM network. Between-group connectivity alterations were computed adopting resting-state functional magnetic resonance imaging (rs-fMRI) data of four groups: PD patients with short disease duration (PD-1, n = 72); PD patients with long disease duration (PD-2, n = 22); healthy controls for PD-1 (HC-1, n = 69); healthy controls for PD-2 (HC-2, n = 22). We explored connectivity differences in the ToM network within and between its three subnetworks: Affective, Cognitive and Core. PD-1 presented a global pattern of decreased functional connectivity within the ToM network, compared to HC-1. The alterations mainly involved the Cognitive and Affective ToM subnetworks and their reciprocal connections. PD-2-those with longer disease duration-showed an increased connectivity spanning the entire ToM network, albeit less consistently in the Core ToM network, compared to both the PD-1 and the HC-2 groups. Functional connectivity within the ToM network is altered in PD. The alterations follow a graded pattern, with decreased connectivity at short disease duration, which broadens to a generalized increase with longer disease duration. The alterations involve both the Cognitive and Affective subnetworks of ToM.

Connectome-based fingerprint of motor impairment is stable along the course of Parkinson's disease.

Functional alterations in brain connectivity have previously been described in Parkinson's disease, but it is not clear whether individual differences in connectivity profiles might be also linked to severity of motor-symptom manifestation. Here we investigated the relevance of individual functional connectivity patterns measured with resting-state fMRI with respect to motor-symptom severity in Parkinson's disease, through a whole-brain, data-driven approach (connectome-based predictive modeling). Neuroimaging and clinical data of Parkinson's disease patients from the Parkinson's Progression Markers Initiative were derived at baseline (session 1, n = 81) and at follow-up (session 2, n = 53). Connectome-based predictive modeling protocol was implemented to predict levels of motor impairment from individual connectivity profiles. The resulting predictive model comprised a network mainly involving functional connections between regions located in the cerebellum, and in the motor and frontoparietal networks. The predictive power of the model was stable along disease progression, as the connectivity within the same network could predict levels of motor impairment, even at a later stage of the disease. Finally, connectivity profiles within this network could be identified at the individual level, suggesting the presence of individual fingerprints within resting-state fMRI connectivity associated with motor manifestations in Parkinson's disease.

Are we social enough? Use of social media among members of the Italian Society of Neurology for the study of dementia.

BACKGROUND: Clinical researchers increasingly embrace social media in their professional lives. The digital revolution has provided new routes for sharing data, disseminating results, and promoting the impact of scientific findings. In this study, we explored the attitude of the members of the Italian Society of Neurology for the study of dementia (SINdem) to use social media with the aim to set up possible corrective actions to maximize digitalization benefits at the individual and community levels. METHOD: An ad hoc designed survey was implemented and distributed to the SINdem and SINdem4Juniors communities. It explored the different use of social media taking into account frequency, type of social media use (active vs passive; professional vs private). Descriptive statistical analyses were performed alongside statistical comparisons to highlight possible differences in the use. RESULTS: We collected 133 answers showing a prominent use of social media in private life (t(132) = 21.1, p < 0.001), with SINdem4Juniors members showing a higher private use compared to the older SINdem colleagues. Professional use was mainly limited to passive activities such as following others' social profiles (t(132) = 11.9, p < 0.001). DISCUSSION: Overall scenario suggests that professional use of social media is very limited in both SINdem and SINdem4juniors communities. This evidence points to an urgent need for training interventions and top-down strategies aimed at improving collaboration, dissemination, and sharing through social media among individuals belonging to the same scientific-professional community.

The FACE test: a new neuropsychological task to assess the recognition of complex mental states from faces.

BACKGROUND: Social cognition deficits are reported in several neurodegenerative diseases, including Parkinson's disease (PD). However, the availability of tasks for the clinical assessment is still limited, preventing the full characterization of socio-cognitive dysfunctions in neurological patients. This study aims to present a new task to assess the recognition of complex mental states from faces (FACE test), reporting normative data for the Italian population and an example of its clinical application to 40 PD patients. METHODS: Two-hundred twenty-nine Italian participants with at least 5 years of education were enrolled. Data were analyzed according to the method of equivalent scores; test-retest reliability and convergent validity were assessed. Two short versions of the FACE test were defined for clinical and research purposes. The prevalence of deficits in the FACE test was computed in the PD sample, as well as correlations with cognitive performance and diagnostic accuracy. RESULTS: Regression analyses revealed significant effects of demographic variables on FACE performance, with younger and more educated individuals showing higher scores. Twenty-eight percent of PD patients showed borderline/pathological performance, which was correlated with emotion recognition/attribution abilities, and attentive-executive functions. The FACE test was accurate (80%) in distinguishing PD patients with socio-cognitive dysfunctions from both controls and PD patients without emotion recognition/attribution difficulties. CONCLUSION: The FACE test represents a new tool assessing the ability to recognize complex mental states from facial expressions. Overall, these results support its use in both clinical and research settings, as well as the presence of affective processing deficits in a subsample of PD patients.

Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective.

Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study.Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2. Ratio of the enantiomers was determined by enantioselective liquid chromatography with tandem mass spectrometry analysis of plasma samples from humans and preclinical species. Drug-drug interaction (DDI) characterisation, evaluation of pharmacological activity on BTK, and off-target screening experiments followed assessing safety of the metabolite.The biotransformation of evobrutinib to M463-2 was determined to be a two-step process with a CYP-mediated oxidation acting to form an epoxide intermediate, which was further hydrolysed by soluble and mitochondrial epoxide hydrolase. Only the (S)-enantiomer was determined to be a major metabolite, the (R)-enantiomer was minor. In vitro studies demonstrated the (S)-enantiomer lacked clinically relevant pharmacological activity, off-target effects and DDIs.The biotransformation of evobrutinib to its major metabolite has been elucidated, with the major (S)-enantiomer being shown to pose no on/off target or DDI risks.

Standardization and normative data for a new test of visual long-term recognition memory.

The assessment of recognition memory is useful in several neurological conditions, but normative data for visual recognition memory of complex figures are still missing for the Italian population. The aim of this study is to present a new short test of visual recognition memory that consists in a supplementary task to be administered after the free delayed recall trial of the Modified Taylor Complex Figure (MTCF). The MTCF-Recognition Trial (MTCF-RT) includes 10 tables, each with a sub-component of the MTCF coupled with two interfering stimuli. Participants are asked to point, for each triplet, the item that was part of the original picture. Normative data were collected from a sample of 280 healthy Italian native speakers ranging in age from 18 to 89 years. The mean recognition score on the MTCF-RT was 9.125 ± 0.996. Results from multiple regression analyses showed that age and education (but not gender) were significant predictors of performance. Therefore, we provided correction grids to adjust raw scores for age and education and computed equivalent scores for the use of the MTCF-RT in the clinical assessment of recognition memory.

Activity of praziquantel enantiomers and main metabolites against Schistosoma mansoni.

A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4'-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4'-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 µg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4'-hydroxypraziquantel were not active at 100 µg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.

The Social and Cognitive Online Training (SCOT) project: A digital randomized controlled trial to promote socio-cognitive well-being in older adults.

OBJECTIVES: Effective prevention programs targeting risk factors for cognitive decline in the elderly are recommended given the progressive increase in the aging of the general population. The Social and Cognitive Online Training (SCOT) project is a randomized, controlled, parallel clinical trial designed to prevent the age-related decline in executive and social functions. METHODS: The study included 60 cognitively healthy older adults (age = 71.8±5.3, education = 12.3±3.7, MoCA = 25.1±2.4). Participants underwent a baseline clinical and neuropsychological assessment and were then assigned to either an experimental group (SCOT) or a non-specific cognitive training group (CON). Both 8-week digital interventions included two individual cognitive training sessions and one group meeting per week. Post-intervention assessment evaluated the efficacy of the training on specific outcome measures: the Tower of London for executive functioning, the Ekman-60 Faces test, and the Mini-Social cognition & Emotional Assessment battery for social cognition. A measure of loneliness was included as an exploratory outcome. RESULTS: Baseline demographic and neuropsychological characteristics were balanced between SCOT (n = 29) and CON (n = 28) groups. Pre-post-intervention analyses showed improvements in executive functioning and social cognition in both groups, without significant interaction effects. Exploratory post-hoc analyses stratifying the SCOT group by training performance showed significant post-training improvements in executive functioning, emotion recognition, and cognitive theory of mind for high-performing participants. DISCUSSION: Results provide preliminary evidence for the beneficial effects of SCOT training, particularly for those who performed best during the training. The SCOT training could represent a new intervention to promote socio-cognitive well-being in the context of active ageing and dementia prevention.

Tango and physiotherapy interventions in Parkinson's disease: a pilot study on efficacy outcomes on motor and cognitive skills.

Pharmacological treatments in Parkinson's disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease's progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.

Early Identification of Different Behavioral Phenotypes in the Behavioral Variant of Frontotemporal Dementia with the Aid of the Mini-Frontal Behavioral Inventory (mini-FBI).

BACKGROUND: The Frontal Behavioral Inventory (FBI) is a questionnaire designed to quantify behavioral changes in frontotemporal dementia (FTD). Literature showed heterogeneous FBI profiles in FTD versus Alzheimer's disease (AD) with variable occurrence of positive and negative symptoms. OBJECTIVE: In this study, we constructed a short FBI version (i.e., mini-FBI) with the aim to provide clinicians with a brief tool for the identification of early behavioral changes in behavioral variant of FTD (bvFTD), also facilitating the differential diagnosis with AD. METHODS: 40 bvFTD and 33 AD patients were enrolled. FBI items were selected based on internal consistency and exploratory factor analysis. Convergent validity of mini-FBI was also assessed. A behavioral index (i.e., B-index) representing the balance between positive and negative mini-FBI symptoms was computed in order to analyze its distribution in bvFTD through a cluster analysis and to compare performance among patient groups. RESULTS: The final version of the mini-FBI included 12 items, showing a significant convergent validity with the Neuropsychiatric Inventory scores (rp = 0.61, p < 0.001). Cluster analysis split patients in four clusters. bvFTD were included in three different clusters characterized by prevalent positive symptoms, both positive and negative symptoms, or prevalent negative behavioral alterations, similar to a subset of AD patients. A fourth cluster included only AD patients showing no positive symptoms. CONCLUSION: The mini-FBI is a valuable easily administrable questionnaire able to early identify symptoms effectively contributing to the bvFTD behavioral syndrome, aiding clinician in diagnosis and management.

Deficits in Emotion Recognition and Theory of Mind in Parkinson's Disease Patients With and Without Cognitive Impairments.

Background: Emotion recognition and social deficits have been previously reported in Parkinson's disease (PD). However, the extent of these impairments is still unclear and social cognition is excluded from the cognitive domains considered in the current criteria for PD mild cognitive impairment (MCI). This study aims to analyze emotion recognition, affective and cognitive theory of mind in early PD patients classified according to Level II MCI criteria, and to evaluate the prevalence of socio-cognitive deficits in this sample. Methods: We enrolled 45 participants with PD, classified as cognitively unimpaired (CU; n = 32) or MCI (n = 13) based on a standard neuropsychological assessment. Social cognitive skills were evaluated through validated tests for emotion recognition (i.e., Ekman 60-faces test, Ek60 Test) and mental states attribution (Story-based Empathy Task, SET) and compared to a group of 45 healthy controls (HC). Between-group differences in social tasks were performed, as well as correlation analyses to assess the relationship between social, cognitive, and clinical variables. Finally, the number of patients with social cognitive impairments in both MCI and CU subgroups was computed based on Italian normative data. Results: Statistical comparison revealed significant differences among groups in the Ek60 test, with MCI obtaining significantly lower scores than HC and CU, especially for negative emotions. Significant differences were detected also in the SET, with lower performance in emotion and intention attribution for both PD groups compared to HC. A significant correlation emerged between the Ek60 test and emotion attribution. Nine patients showed poor performance at social tasks, five of them being classified as PD-CU. Discussion: Parkinson's disease cognitive profile was characterized by emotion recognition and attribution deficits. These results, as well as the detection of CU patients with isolated socio-cognitive impairments, underline the importance of assessing social cognition in PD as a possible early marker of cognitive decline.

The Role of Social Cognition Abilities in Parkinson's Disease in the Era of COVID-19 Emergency.

Introduction: Parkinson's Disease (PD) is characterized by motor and non-motor symptoms, among which deficits in social cognition might affect ~20% of patients. This study aims to evaluate the role of social cognitive abilities in the perceived impact of COVID-19 emergency, and the effects of lockdown measures on patients' social network and caregivers' burden. Methods: Fourteen PD patients performed a neuropsychological battery including sociocognitive tasks before the introduction of COVID-19 restrictive measures (i.e., social distancing and isolation). A structured interview through an online platform was performed in the last 2 weeks of the first lockdown phase to assess patients' health status, perception of COVID-19 emergency, changes in caregivers' burden, and patients' social isolation. Non-parametric analyses were performed to evaluate the association between social skills and patients' COVID-19 perception, as well as the effects of restrictive measures. Results: At baseline evaluation, half of the PD patients showed sociocognitive dysfunctions, mainly on mentalizing abilities. Patients with impaired social cognition skills showed a significantly lower concern on the possible effects of COVID-19 on their health. Caregiver burden and patients' social network remained stable during the lockdown. Conclusion: These preliminary results underline that PD sociocognitive dysfunctions might affect patients' abilities to estimate the effects of COVID-19 infection. However, the lack of a significant increase in caregivers' burden and social isolation suggests, in our sample, a good coping to COVID-19 emergency. Since COVID-19 pandemic can have direct and indirect severe consequences in patients with PD, the development of educational and preventive programs is recommended.