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Background: The Italian Interceptor project is aimed at identifying a prodromal dementia phase and developing a nationwide organizational model. This study compares the sociodemographic and neuropsychological characteristics of mild cognitive impairment non-converters (MCI-NC) and MCI-converters (MCI-C) to dementia, including Alzheimer's disease (AD), enrolled during the Interceptor project., Methods: Sociodemographic, clinical, and neuropsychological data of MCI individuals were collected at baseline (December 2018 to October 2020) and every six-month follow-up visit for 3 years. Logistic regression and Random Forest classifier were used to describe the study population., Results: From 356 participants, 104 were MCI-C, whereas 252 were MCI-NC. Compared to MCI-NC, MCI-C were predominantly female (p = 0.020), older (p < 0.001), and more cognitively impaired (p < 0.001). Higher physical activity was protective for progression (p < 0.001), but no difference was observed for smoking exposure (p = 0.312) between the two groups. Similar results were found for AD individuals compared to MCI-C/non-AD. The ROC curve based on a Random Forest classifier distinguishing MCI-C from MCI-NC showed an area under the curve (AUC) of 0.7347., Conclusions: Our findings confirm previous evidence in literature and may increase the insight on dementia pathology and help in defining intervention strategies to prevent or slow down disease progression., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer's Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI)., Methods: The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse ® G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles., Results: We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects., Conclusions: Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in compliance with the Declaration of Helsinki for the protection of human participants and was approved by the Ethics Committee of Fondazione Policlinico Universitario Agostino Gemelli (approval code 2251). Additionally, approval was obtained from all local ethics committees of the participating clinical centres. Written informed consent was obtained from participants. Consent for publication: N/A. Competing interests: A.P. is an employee of Fujirebio., (© 2025. The Author(s).)

Background: Subcortical brain mapping in awake glioma surgery might optimize the extent of resection while minimizing neurological morbidity, but it requires a correct interpretation of responses evoked during surgery. To define, with a systematic review: 1) a comprehensive 'map' of the principal white matter bundles involved in awake surgery on language-related networks, describing the most employed tests and the expected responses; 2) In linguistics, a false friend is a word in a different language that looks or sounds like a word in given language but differs significantly in meaning. Similarly, our aim is to give the surgeons a comprehensive review of potentially misleading responses, namely "false friends", in subcortical language mapping., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Standardized data extraction was conducted., Results: Out of a total of 224 initial papers, 67 were included for analysis. Expected responses, common tests, and potential "false friends" were recorded for each of the following white matter bundles: frontal aslant tract, superior and inferior longitudinal fascicles, arcuate fascicle, inferior fronto-occipital fascicle, uncinate fascicle. Practical examples are discussed to underline the risk of intraoperative fallouts ("false friends") that might lead to an early interruption (false positive) or a risky surgical removal (false negative)., Conclusions: This paper represents a critical review of the present status of subcortical awake mapping and underlines practical "false-friend" in mapping critical crossroads in language-related networks., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer's disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future., Methods: The ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50-85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ([ 18 F]FDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1-40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram., Discussion: This paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions., Trial Registration: ClinicalTrials.gov NCT03834402. Registered on February 8, 2019., (© 2024. The Author(s).)

Background: It is known that psychosocial distress affects the morbidity and mortality of patients with cardiovascular disease of every age. The aim of this study was to produce novel information on how psychological distress can influence cardiovascular performance in patients after cardiac surgery undergoing multidisciplinary cardiac rehabilitation., Methods: Patients (n = 57) admitted after cardiac surgery for valvular or coronary disease underwent, within 5 days of admission, the Symptom Checklist-90-Revised (SCL-90-R) self-report questionnaire to measure psychiatric symptoms and the 12-item General Health Questionnaire (GHQ-12) to assess the level of psychological distress. The Positive Symptom Distress Index (PSDI) was measured to indicate the amplitude of symptom distress. Cardiovascular performance was assessed by a 6 min walking test (6MWT) at admission and discharge, and oxygen consumption (VO2 max) was derived., Results: Within the SCL-90-R score, somatic symptoms (47.4%), depressive and anxiety symptoms (36.8% and 33.3%, respectively), symptoms of phobic anxiety (21.1%), and psychoticism (24.6%) were over-represented. As for the GHQ-12, 75.4% of the sample reported an abnormally negative perception of their health status. An inverse correlation was shown between the variation in 6MWT and SCL depression ( p = 0.048), PSDI ( p = 0.022), and the GHQ-12 ( p = 0.040). Similarly, an inverse correlation was shown between the variation in the VO2 max, GHQ-12 ( p = 0.041), and the PSDI ( p = 0.023)., Conclusions: Post-cardiac surgery cardiac rehabilitation was associated with increased symptoms of psychological discomfort, as compared with the general population. The amplitude of psychological distress, depression, and hostility are associated with limited improvement in performance. These data strengthen the need for psychological support during cardiac rehabilitation programs.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector , enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions., Competing Interests: CH-H was employed by BrainSymph AS. VAy, JP, and LP were employed by Lurtis Rules S.L. EC was employed by Pre Diagnostics AS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haraldsen, Hatlestad-Hall, Marra, Renvall, Maestú, Acosta-Hernández, Alfonsin, Andersson, Anand, Ayllón, Babic, Belhadi, Birck, Bruña, Caraglia, Carrarini, Christensen, Cicchetti, Daugbjerg, Di Bidino, Diaz-Ponce, Drews, Giuffrè, Georges, Gil-Gregorio, Gove, Govers, Hallock, Hietanen, Holmen, Hotta, Kaski, Khadka, Kinnunen, Koivisto, Kulashekhar, Larsen, Liljeström, Lind, Marcos Dolado, Marshall, Merz, Miraglia, Montonen, Mäntynen, Øksengård, Olazarán, Paajanen, Peña, Peña, Peniche, Perez, Radwan, Ramírez-Toraño, Rodríguez-Pedrero, Saarinen, Salas-Carrillo, Salmelin, Sousa, Suyuthi, Toft, Toharia, Tveitstøl, Tveter, Upreti, Vermeulen, Vecchio, Yazidi and Rossini.)

Objective: Self-assessment scales are broadly used to evaluate empathy in neurological patients, but it is conceivable that some discrepancy with caregiver evaluation may emerge as consequence of reduced self-awareness. The aim of the present study was to verify the presence of discrepancies in the self-assessment of empathy in subjects with mild cognitive impairment (MCI) and to explore their neural correlates., Method: Twenty MCI patients and 38 healthy controls (HCs) underwent the Interpersonal Reactivity Index (IRI), exploring the following four aspects of empathy: perspective taking (PT), fantasy, empathic concern, and personal distress. The questionnaire was administered in two modalities: self-administered, and administered to an informant, and the scores were compared. The correlation between discrepancies and regional cortical thickness was assessed., Results: The self-administered version of IRI showed higher PT scores in MCI as compared to HC ( p = .017), with no differences detected in the other subscales. The difference between the scores obtained in the self-administered and in the informant-administered IRI-PT was significantly higher in MCI than in HCs ( p = .006)., Conclusion: The self-assessment of empathy in subjects with MCI may be misleading because of a tendency toward an overestimation of the PT ability, typically considered as a cognitive component of empathy. Our results may reflect a particular aspect of reduced self-awareness in MCI subjects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Impairment of episodic memory is largely considered the main cognitive marker of prodromic Alzheimer's disease (AD). Nevertheless, the neuropathological process in AD starts several years before and, apart from biomarkers well defined in the Amyloid (A), Tauopathy (T), Neurodegeneration (N) framework, early clinical and neuropsychological markers able to detect mild cognitive impairment (MCI) due to AD before the appearance of memory disorders are lacking in clinical practice. Investigations on semantic memory have shown promising results in providing an earlier marker of dementia in MCI patients., Methods: A total of 253 MCI subjects were followed up every 6 months for 6 years-186 converted to dementia and 67 remained stable at the sixth year of follow-up. Twenty-seven patients progressed in the first 2 years (fast converters), 107 in the third to fourth year (intermediate converters), and 51 after the fourth year of follow-up (slow converters)., Results: Stable MCI subjects performed better than fast decliners in Mini-Mental State Examination (MMSE), several long-term memory scores, and category verbal fluency test (CFT); stable and intermediate converters differ only in MMSE and CFT tests; and stable and slow converters differ only in MMSE and phonological/semantic discrepancy score., Conclusion: Early impairment of semantic memory could predict the evolution to AD before the onset of episodic memory disorders, and the discrepancy between phonological and semantic verbal fluency could be able to detect this impairment in advance in respect of simple CFT tests. The assessment of different aspects of semantic memory and its degradation could represent an early cognitive marker to intercept MCI due to AD in clinical practice., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The behavioural variant of frontotemporal dementia (bvFTD) is primarily characterized by deficits in social behaviour and theory of mind (ToM). Although a consensus has been reached on the roles of the cerebellum in social cognition and ToM, its specific contribution to social impairments of bvFTD has never been specifically investigated. The aim of this study was to assess cerebellar structural and functional changes in patients with bvFTD and their potential association with ToM deficits of patients. Therefore, 15 patients with bvFTD and 34 healthy subjects underwent an MRI examination. Voxel-based morphometry was used to assess cerebellar (GM) changes, and a seed-based analysis was performed to test cerebello-cerebral functional connectivity (FC). The performance of bvFTD patients in a ToM task was then correlated with FC patterns. Compared to healthy subjects, patients with bvFTD showed significant cerebellar GM loss specifically involving cerebellar Crus I-II. Additionally, FC changes FC were observed between the cerebellum and cerebral regions related to ToM. Interestingly, patterns of changes in cerebello-cerebral FC correlated with altered ToM performances explored using the "Reading the Mind with the Eyes" test (RMET) of patients. The present findings suggest that specific changes in cerebello-cerebral FC may underlie ToM alterations in patients with bvFTD.