NEUROPSYCHIATRIC SYMPTOMS OF DEMENTIA AND BIOMARKERS OF NEURODEGENERATION: CSF TAU AND MRI

Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry.Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry

The impact of different goodwill accounting methods on stock prices: A comparison of amortization and impairment-only methodologies

In March 2020, the IASB issued a discussion paper – ‘Business Combinations – Disclosures, Goodwill and Impairment’ – which discussed, inter alia, whether to introduce a sort of counterreformation of IAS 36 that might lead to the reintroduction of goodwill amortization. Among other things, the IASB, leveraging key findings from academic research, questioned a) the disclosure provided by entities applying IFRS 3 requirements and b) the timing of impairment write-downs and their overal1l magnitude. The main goal of this study, focusing on a large sample of European listed companies since the adoption of IAS in 2005, is to test the value relevance of goodwill under the current accounting framework and the alternative hypothesis of an amortization regime. Our findings show that the information provided by listed companies to market investors under the current accounting regime (verification at least annually of the recoverability of the value of the goodwill carrying amount through the impairment test) – the level of goodwill before and post impairment, as well as goodwill write downs – is value relevant and contributes to explain the level of the market to tangible book value multiple. On the contrary, simulating the alternative accounting scenario of goodwill amortization, we found that the information conveyed to market investor would not be value relevant, with the amortization itself added back to the multiple. The results support the current accounting framework and indicate that the best way to improve goodwill accounting is by enforcing present rules. This study aims to provide a multidimensional contribution to the current debate within the IASB, leveraging the largest database in Europe

Pre-existing mental health disorders and fear of COVID-19 pandemic: Data from a phone survey in community-dwelling older adults recruited in the NutBrain study

Background: COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people. Materials and methods: In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders. Results: Out of the 351 respondents (mean age 73.5 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had Frontiers in Psychiatry 01 frontiersin.org Perdixi et al. 10.3389/fpsyt.2022.995308 depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39–4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25–4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37–7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17). Conclusion: Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals

Advancing Italian Biomedical Information Extraction with Large Language Models: Methodological Insights and Multicenter Practical Application

The introduction of computerized medical records in hospitals has reduced burdensome operations like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting them from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation, using automated text-mining pipelines. In this work, we created the first Italian neuropsychiatric Named Entity Recognition dataset, PsyNIT, and used it to develop a Large Language Model for this task. Moreover, we conducted several experiments with three external independent datasets to implement an effective multicenter model, with overall F1-score 84.77%, Precision 83.16%, Recall 86.44%. The lessons learned are: (i) the crucial role of a consistent annotation process and (ii) a fine-tuning strategy that combines classical methods with a "few-shot" approach. This allowed us to establish methodological guidelines that pave the way for future implementations in this field and allow Italian hospitals to tap into important research opportunities

Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias

INTRODUCTION: Neural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. The Virtual Brain (TVB) modeling, by exploiting structural and functional magnetic resonance imaging (MRI), yields mesoscopic parameters of connectivity and synaptic transmission. METHODS: We used TVB to simulate brain networks, which are key for human brain function, in Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks. RESULTS: The pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles. DISCUSSION: These TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches

Fast algorithm for real-time rings reconstruction

The GAP project is dedicated to study the application of GPU in several contexts in which real-time response is important to take decisions. The definition of real-time depends on the application under study, ranging from answer time of μs up to several hours in case of very computing intensive task. During this conference we presented our work in low level triggers [1] [2] and high level triggers [3] in high energy physics experiments, and specific application for nuclear magnetic resonance (NMR) [4] [5] and cone-beam CT [6]. Apart from the study of dedicated solution to decrease the latency due to data transport and preparation, the computing algorithms play an essential role in any GPU application. In this contribution, we show an original algorithm developed for triggers application, to accelerate the ring reconstruction in RICH detector when it is not possible to have seeds for reconstruction from external trackers

DNA2 drives processing and restart of reversed replication forks in human cells

Accurate processing of stalled or damaged DNA replication forks is paramount to genomic integrity and recent work points to replication fork reversal and restart as a central mechanism to ensuring high-fidelity DNA replication. Here, we identify a novel DNA2- and WRN-dependent mechanism of reversed replication fork processing and restart after prolonged genotoxic stress. The human DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks with a 5'-to-3' polarity and promote replication restart, thus preventing aberrant processing of unresolved replication intermediates. Unexpectedly, EXO1, MRE11, and CtIP are not involved in the same mechanism of reversed fork processing, whereas human RECQ1 limits DNA2 activity by preventing extensive nascent strand degradation. RAD51 depletion antagonizes this mechanism, presumably by preventing reversed fork formation. These studies define a new mechanism for maintaining genome integrity tightly controlled by specific nucleolytic activities and central homologous recombination factors

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

BPSDiary study protocol: a multi-center randomized controlled trial to compare the efficacy of a BPSD diary vs. standard care in reducing caregiver's burden

Behavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological and behavioral abnormalities seen in persons with dementia (PwD), significantly impacting their quality of life and that of their caregivers. Current assessment tools, such as the Neuropsychiatric Inventory (NPI), are limited by recall bias and lack of direct observation. This study aims to overcome this limitation by making caregiver reports more objective through the use of a novel instrument, referred to as the BPSDiary. This randomized controlled trial will involve 300 caregiver-PwD dyads. The objective is to evaluate whether the use of the BPSDiary could significantly reduce caregiver burden, assessed using the Zarit Burden Interview (ZBI), compared to usual care. The study will include adult PwD, caregivers living with or close to the patient, and BPSD related to the HIDA (hyperactivity, impulsivity, irritability, disinhibition, aggression, agitation) domain. Caregivers randomized to the intervention arm will use the BPSDiary to record specific BPSD, including insomnia, agitation/anxiety, aggression, purposeless motor behavior, and delusions/hallucinations, registering time of onset, severity, and potential triggers. The primary outcome will be the change in ZBI scores at 3 months, with secondary outcomes including changes in NPI scores, olanzapine equivalents, NPI-distress scores related to specific BPSD domains, and caregiver and physician satisfaction. The study will be conducted in 9 Italian centers, representing diverse geographic and sociocultural contexts. While potential limitations include the relatively short observation period and the focus on specific BPSD disturbances, the BPSDiary could provide physicians with objective data to tailor appropriate non-pharmacological and pharmacological interventions. Additionally, it may empower caregivers by encouraging reflection on BPSD triggers, with the potential to improve the quality of life for both PwD and their caregivers.Trial registryNCT05977855