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BACKGROUND: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. METHODS: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. DISCUSSION: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. TRIAL REGISTRATION: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741).
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Disfunción Cognitiva , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/terapia , Pacientes Ambulatorios , Multimorbilidad , Femenino , Trastornos Neurocognitivos/diagnóstico , Masculino , Tamizaje Masivo/métodos , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , DemenciaRESUMEN
BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Pruebas Neuropsicológicas , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Femenino , Masculino , Pruebas Neuropsicológicas/normas , Anciano , Italia , Persona de Mediana Edad , Reproducibilidad de los Resultados , Anciano de 80 o más AñosRESUMEN
The introduction of computerized medical records in hospitals has reduced burdensome activities like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting data from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation by 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 Transformers-based model. Moreover, we collected and leveraged 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 "low-resource" approach. This allowed us to establish methodological guidelines that pave the way for Natural Language Processing studies in less-resourced languages.
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Minería de Datos , Lenguaje , Humanos , Minería de Datos/métodos , Registros Electrónicos de Salud , Italia , Procesamiento de Lenguaje Natural , Estudios Multicéntricos como AsuntoRESUMEN
Objective: We investigated how physical activity can be effectively promoted with a message-based intervention, by combining the explanatory power of theory-based structural equation modeling with the predictive power of data-driven artificial intelligence. Methods: A sample of 564 participants took part in a two-week message intervention via a mobile app. We measured participants' regulatory focus, attitude, perceived behavioral control, social norm, and intention to engage in physical activity. We then randomly assigned participants to four message conditions (gain, non-loss, non-gain, loss). After the intervention ended, we measured emotions triggered by the messages, involvement, deep processing, and any change in intention to engage in physical activity. Results: Data analysis confirmed the soundness of our theory-based structural equation model (SEM) and how the emotions triggered by the messages mediated the influence of regulatory focus on involvement, deep processing of the messages, and intention. We then developed a Dynamic Bayesian Network (DBN) that incorporated the SEM model and the message frame intervention as a structural backbone to obtain the best combination of in-sample explanatory power and out-of-sample predictive power. Using a Deep Reinforcement Learning (DRL) approach, we then developed an automated, fast-profiling strategy to quickly select the best message strategy, based on the characteristics of each potential respondent. Finally, the fast-profiling method was integrated into an AI-based chatbot. Conclusion: Combining the explanatory power of theory-driven structural equation modeling with the predictive power of data-driven artificial intelligence is a promising strategy to effectively promote physical activity with message-based interventions.
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BACKGROUND: Fibromyalgia patients can benefit from music approaches as complementary treatments. In the literature, it was shown that these interventions managed pain conditions as well as reduced complaints, increased relaxation, and improved moods. OBJECTIVE: This study aimed at evaluating music therapy, in the form of therapeutic music listening, specifically for patients with fibromyalgia, to treat chronic pain by reducing pain perception, increasing well-being, and improving quality of life. METHODS: Twenty-four patients with fibromyalgia were recruited to take part in this feasibility pilot study that adopted a between-subject and within-subject design. Participants were randomised into three groups: (1) standard care, (2) standard care plus preferred music listening, (3) standard care plus Melomics-Health music listening, composed by an algorithm. Participants in experimental groups listened to 30 min of music at home, twice a day for a month. Patients' perceptions of changes following the listening, the intensity of pain and its interference in their lives, physical and mental well-being, and reported attitudes towards listening to music were evaluated respectively through the patients' global impression of change, the brief pain inventory, the Short Form Healthy Survey-12, and the cognitive behavioural assessment-outcome evaluation. RESULTS: The study showed that music listening can significantly affect mental well-being compared to no music. Moreover, the effects in the Melomics-Health group are maintained at follow-up. No significant effect on pain perception was noted. CONCLUSIONS: The study provides information supporting a possible role of music listening in improving well-being of patients with fibromyalgia.
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Dolor Crónico , Fibromialgia , Humanos , Fibromialgia/terapia , Proyectos Piloto , Calidad de Vida , Estudios de FactibilidadRESUMEN
SUMMARY: This review aimed at exploring how music listening-based approach can be effective on physiological, cognitive and behavioural aspects, with specific reference to the domain of dementias. Music listening can be considered one of the most common approaches in dementia care, frequently in combination with other non-pharmacological treatments. This type of intervention may allow persons with dementia to work on the organization and regulation of their emotions thanks to the mediation of the sonorous-musical element. Methods. Two independent researchers performed literature search by consulting the PUBMED database and the Cochrane Register of randomized controlled trials (articles written in English and published from January 1st 2000 to February 28th 2022 were considered as eligible). Results. Twelve articles met the inclusion criteria and were included in this review. The selected studies highlighted some effects of music listening in people with moderate to severe dementia. Assuming a clinical point of view, the results showed how music listening intervention could bring benefits on the behavioural and psychological symptoms of dementia, also if not always statistically significant. Discussion/Conclusion. The study focused on the need to define clear criteria of music listening programs selection and administration, but also on the involvement of trained music therapists in planning and managing the music listening-based interventions. Music listening interventions should be developed by implementing evidence-based practice and integrating research in the field. The identification of specific musical elements connected with the therapeutic outcome is a key point for the music therapy future.
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Demencia , Musicoterapia , Música , Humanos , Musicoterapia/métodos , Demencia/terapia , Demencia/psicologíaRESUMEN
Background: Cognitive dysfunctions, both subjective and detectable at psychometric testing, may follow SARS-CoV-2 infection. However, the ecological-functional relevance of such objective deficits is currently under-investigated. This study thus aimed at investigating the association between objective cognitive measures and both physical and cognitive, ecological-functional outcomes in post-COVID-19. Methods: Forty-two COVID-19-recovered individuals were administered the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The Functional Independence Measure (FIM) was adopted to assess functional-ecological, motor/physical (FIM-Motor) and cognitive (FIM-Cognitive) outcomes at admission (T0) and discharge (T1). Results: When predicting both T0/T1 FIM-total and-Motor scores based on MMSE/MoCA scores, premorbid risk for cognitive decline (RCD) and disease-related features, no model yielded a significant fit. However, the MoCA - but not the MMSE significantly predicted T0/T1 FIM-Cognitive scores. The MoCA was significantly related only to T0/T1 FIM-Cognitive Memory items. Discussion: Cognitive measures are not associated with physical/motor everyday-life outcomes in post-COVID-19 patients. The MoCA may provide an ecological estimate of cognitive functioning in this population.
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This study explores the association between psychiatric symptoms following COVID-19 and demographic, disease-related and premorbid clinical confounders. Global cognition, depression, anxiety and PTSD features were assessed in 152 post-COVID-19 patients, subdivided into being at risk for brain disorders or not. In both groups, clinically meaningful depression, anxiety and PTSD symptoms were mildly-to-moderately frequent (4-45%). No demographic or clinical variables predicted psychiatric measures (except for lower age predicting higher anxiety levels). Depression, anxiety and PTSD measures were associated among each other. Hence, depression-, anxiety- and PTSD-spectrum disturbances in COVID-19 survivors are likely to be unassociated with disease-related and premorbid features.
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COVID-19 , Trastornos por Estrés Postraumático , Ansiedad/epidemiología , Ansiedad/psicología , Trastornos de Ansiedad/psicología , Depresión/epidemiología , Depresión/psicología , Humanos , Estudios Retrospectivos , Trastornos por Estrés Postraumático/psicologíaRESUMEN
BACKGROUND: Episodic long-term memory (LTM) difficulties/deficits are frequent in COVID-19-recovered patients and negatively impact on prognosis and outcome. However, little is known about their semiology and prevalence, also being still debated whether they arise from primary amnesic features or are secondary to dysexecutive/inattentive processes and disease-related/premorbid status. Hence, this study aimed at (1) assessing LTM functioning in post-infectious SARS-CoV-2 patients by accounting for premorbid and disease-related confounders and (2) exploring its cognitive etiology. METHODS: Measures of global cognition (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)) and LTM (Babcock Memory Test (BMT)) of fifty-four COVID-19-recovered patients were retrospectively collected. Patients were subdivided into those being already at risk or not for cognitive decline (RCD + ; RCD -). Cognitive measures were converted into equivalent scores (ESs). RESULTS: LTM sub-clinical/clinical deficits (ESs = 0/1) were mildly-to-moderately prevalent in both RCD + (MoCA-Memory, 31.8%; BMT, 31.8%) and RCD - (MoCA-Memory, 28.6%; BMT, 39.3%) patients. MMSE and MoCA total scores, but not the MoCA-Attention subtest, were associated with the BMT. RCD + asymptomatic patients performed better on the BMT (p = .033) than those requiring O2 therapy (but not ventilation). DISCUSSION: COVID-19-recovered individuals might show LTM deficits of both primary and secondary etiology and should be thus screened for them, especially those having suffered mid-to-moderate COVID-19 and those already being at risk for cognitive decline. Both I- and II-level measures of verbal LTM can be adopted, although the former might be more sensitive.
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COVID-19 , Disfunción Cognitiva , Humanos , Memoria a Largo Plazo , Pruebas Neuropsicológicas , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: The novel human coronavirus (SARS-CoV-2) shows neurotropism and systemically affects the central nervous system (CNS). Cognitive deficits have been indeed reported as both short- and long-term sequelae of SARS-CoV-2 infection. However, the association between these disturbances and background/disease-related clinical features remains elusive. This work aimed at exploring how post-infective cognitive status relates to clinical/treatment outcomes by controlling for premorbid/current risk factors for cognitive deficits. METHODS: Cognitive measures (Mini-Mental State Examination, MMSE) of N=152 COVID-19 patient were retrospectively assessed in relation to disease severity, intensive care unit (ICU) admission, steroidal treatment, and occurrence of other viral/bacterial infections by controlling for remote/recent/COVID-19-related risk factors for cognitive deficits (at-risk vs. not-at-risk: Neuro+ vs. Neuro-). RESULTS: Descriptively, impaired MMSE performances were highly prevalent in mild-to-moderate patients (26.3%). ICU-admitted patients made less errors (p=.021) on the MMSE than those not admitted when partialling out risk factors and age-the latter negatively influencing performances. When addressing Neuro- patients only, steroidal treatment appears to improve MMSE scores among those suffering from other infections (p=.025). DISCUSSION: Cognitive sequelae of COVID-19 are likely to arise from a complex interplay between background/clinical premorbid features and disease-related/interventional procedures and outcomes. Mild-to-moderate patients requiring assistive ventilation who however are not admitted to an ICU are more likely to suffer from cognitive deficits-despite their etiology remaining elusive.
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COVID-19 , Cognición , Humanos , Unidades de Cuidados Intensivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Growing evidence highlights the potential of innovative rehabilitative interventions such as cognitive remediation and neuromodulation, aimed at reducing relapses in Alcohol Use Disorder (AUD). Enhancing their effectiveness requires a thorough description of the neural correlates of cognitive alterations in AUD. Past related attempts, however, were limited by the focus on selected neuro-cognitive variables. We aimed to fill this gap by combining, in 22 AUD patients and 18 controls, an extensive neuro-cognitive evaluation and metrics of intrinsic connectivity as highlighted by resting-state brain activity. We addressed an inherent property of intrinsic activity such as intra-network coherence, the temporal correlation of the slow synchronous fluctuations within resting-state networks, representing an early biomarker of alterations in the functional brain architecture underlying cognitive functioning. AUD patients displayed executive impairments involving working-memory, attention and visuomotor speed, reflecting abnormal coherence of activity and grey matter atrophy within default mode, in addition to the attentional and the executive networks. The stronger relationship between fronto-lateral coherent activity and executive performance in patients than controls highlighted possible compensatory mechanisms counterbalancing the decreased functionality of networks driving the switch from automatic to controlled behavior. These results provide novel insights into AUD patients' cognitive impairments, their neural bases, and possible targets of rehabilitative interventions.
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BACKGROUND: Due to SARS-CoV-2-related encephalopathic features, COVID-19 patients may show cognitive sequelae that negatively affect functional outcomes. However, although cognitive screening has been recommended in recovered individuals, little is known about which instruments are suitable to this scope by also accounting for clinical status. This study thus aimed at comparatively assessing the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in detecting cognitive deficits in post-COVID-19 patients premorbidly/contextually being or not at risk for cognitive deficits (RCD + ; RCD-). METHODS: Data from N = 100 COVID-19-recovered individuals having been administered both the MMSE and the MoCA were retrospectively analyzed separately for each group. RCD ± classification was performed by taking into consideration both previous and disease-related conditions. Equivalent scores (ESs) were adopted to examine classification performances of the two screeners. RESULTS: The two groups were comparable as for most background and cognitive measures. MMSE or MoCA adjusted scores were mostly unrelated to disease-related features. The two screeners yielded similar estimates of below-cut-off performances-RCD + : MMSE: 20%, MoCA: 23.6%; RCD-: MMSE: 2.2%, MoCA: 4.4%. However, agreement rates dropped when also addressing borderline, "low-end" normal, and normal ability categories-with the MoCA attributing lower levels than the MMSE (RCD + : Cohen's k = .47; RCD-: Cohen's k = .17). DISCUSSION: Although both the MMSE and the MoCA proved to be equally able to detect severe cognitive sequelae of SARS-CoV-2 infection in both RCD + and RCD- patients, the MoCA appeared to be able to reveal sub-clinical defects and more sharply discriminate between different levels of ability.
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COVID-19 , Disfunción Cognitiva , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Humanos , Pruebas de Estado Mental y Demencia , Pruebas Neuropsicológicas , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Decreased punishment sensitivity in alcohol use disorder (AUD) might reflect a reduction in the typical human tendency to overweigh negative choice outcomes compared with equivalent positive ones, that is, 'loss aversion.' While this hypothesis is supported by previous reports of reduced loss aversion in AUD, it is still unknown whether such decreased sensitivity to prospective losses represents a specific facet of altered decision-making or a secondary effect of executive/working-memory impairments. We addressed this issue by assessing whether lower loss aversion in 22 AUD patients compared with 19 healthy controls is explained by their differential executive or working-memory performance and by investigating its neural basis in terms of grey matter density and cortical thickness via voxel- and surface-based morphometry, respectively. A significant decrease of loss aversion in patients, unrelated to their impaired executive/working-memory performance, reflected the reduction of posterior fronto-medial grey matter density and right frontopolar cortical thickness. Rather than their executive deficits, patients' reduced loss aversion reflects the structural damage of the posterior fronto-medial cortex previously associated with solving conflicts at the response level, where earlier functional magnetic resonance imaging (fMRI) studies have shown a 'neural loss aversion' pattern of steeper deactivation for losses than activation for gains, and of the frontopolar cortex in charge of managing competing goals. These findings highlight possible directions for addressing AUD patients' high relapse rate, for example, cognitive-behavioural rehabilitative interventions enhancing the awareness of the adverse outcomes of addiction or neurostimulation protocols targeting the regions processing their salience.
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Alcoholismo/patología , Atrofia/patología , Función Ejecutiva/efectos de los fármacos , Sustancia Gris/patología , Memoria a Corto Plazo/efectos de los fármacos , Adulto , Encéfalo/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The coronavirus disease 19 (COVID-19) can cause neurological, psychiatric, psychological, and psychosocial impairments. Literature regarding cognitive impact of COVID-19 is still limited. The aim of this study was to evaluate cognitive deficits and emotional distress among COVID-19 and post-COVID-19 patients who required functional rehabilitation. Specifically, this study explored and compared cognitive and psychological status of patients in the subacute phase of the disease (COVID-19 group) and patients in the postillness period (post-COVID-19 group). Forty patients admitted to rehabilitation units were enrolled in the study and divided into two groups according to the phase of the disease: (a) COVID-19 group (n = 20) and (b) post-COVID-19 group (n = 20). All patients underwent a neuropsychological assessment including Mini-Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Impact of Event Scale-Revised (IES-R). A larger part of the COVID group showed neuropsychological deficits in the total MMSE (35%) compared to the post-COVID group (5%), whereas the majority of both groups (75-70%) reported cognitive impairments in the total MoCA. The post-COVID group reported significantly higher score in MMSE subtests of language (p = 0.02) and in MoCA subtests of executive functions (p = 0.05), language (p = 0.01), and abstraction (p = 0.02) compared to the COVID group. Regarding emotional disturbances, ~40% of patients presented with mild to moderate depression (57.9-60%). The post-COVID-19 group reported significantly higher levels of distress at the IES-R compared to the COVID group (p = 0.02). These findings highlight the gravity of neuropsychological and psychological symptoms that can be induced by COVID-19 infection and the need for tailored rehabilitation, including cognitive training and psychological support.
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Alcohol Use Disorder (AUD) is a chronic relapsing condition characterized by excessive alcohol consumption despite its multifaceted adverse consequences, associated with impaired performance in several cognitive domains including decision-making. While choice deficits represent a core component of addictive behavior, possibly consecutive to brain changes preceding the onset of the addiction cycle, the evidence on grey-matter and white-matter damage underlying abnormal choices in AUD is still limited. To fill this gap, we assessed the neurostructural bases of decision-making performance in 22 early-abstinent alcoholic patients and 18 controls, by coupling the Cambridge Gambling Task (CGT) with quantitative magnetic resonance imaging metrics of grey-matter density and white-matter integrity. Regardless of group, voxel based morphometry highlighted an inverse relationship between deliberation time and grey-matter density, with alcoholics displaying slower choices related to grey-matter atrophy in key nodes of the motor control network. In particular, grey-matter density in the supplementary motor area, reduced in alcoholic patients, explained a significant amount of variability in their increased deliberation time. Tract-based spatial statistics revealed a significant relationship between CGT deliberation time and all white-matter indices, involving the most relevant commissural, projection and associative tracts. The lack of choice impairments other than increased deliberation time highlights reduced processing speed, mediated both by grey-matter and white-matter alterations, as a possible marker of a generalized executive impairment extending to the output stages of decision-making. These results pave the way to further studies aiming to tailor novel rehabilitation strategies and assess their functional outcomes.
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Alcoholismo , Sustancia Blanca , Alcoholismo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Cognición , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagenRESUMEN
INTRODUCTION: Common assessment tools for aphasia evaluate single language impairments but not their functional impact on patient's communication skills in daily life. The lack of tools focused on ecological aspects might affect the choice of rehabilitative trainings. The Communicative Effectiveness Index (CETI) represents an attempt to assess the communicative abilities in "ecologic" context. This study aimed to explore psychometrics properties of the Italian translation and adaptation of CETI (I-CETI). METHODS: Sixty-eight patients with aphasia due to left hemispheric stroke admitted to post-acute rehabilitation units and their relatives were included in the study. Data were collected in three different sessions. At study entry, patients were assessed for language, depression, and functional abilities, while their caregivers and speech therapists independently completed the I-CETI to assess inter-rater agreement (baseline). One week later, caregivers and speech therapists completed again I-CETI, to assess test-retest reliability (T1). Last, at discharge, patients completed again the evaluation protocol, and caregivers and speech therapists completed I-CETI (T2). RESULTS: I-CETI showed high internal validity, excellent reliability, and good correlation between scores obtained by speech therapists and caregivers. Moreover, scores of I-CETI had quite good correlations with a traditional tool to assess language, and with measures of functional independence both at study entry and at discharge. DISCUSSION: I-CETI showed good psychometric proprieties. These results allowed considering I-CETI as a reliable tool to assess effects of speech treatments on the communicative abilities in patients with aphasia. Furthermore, I-CETI might help clinicians to develop treatments more tailored on the "ecologic" difficulties of patients.
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Afasia , Accidente Cerebrovascular , Afasia/diagnóstico , Afasia/etiología , Comunicación , Humanos , Italia , Psicometría , Reproducibilidad de los Resultados , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Encuestas y CuestionariosRESUMEN
Alcohol Use Disorders (AUD) is associated with negative consequences on global functioning, likely reflecting chronic changes in brain morphology and connectivity. Previous attempts to characterize cognitive impairment in AUD addressed patients' performance in single domains, without considering their cognitive profile as a whole. While altered cognitive performance likely reflects abnormal white-matter microstructural properties, to date no study has directly addressed the relationship between a proxy of patients' cognitive profile and microstructural damage. To fill this gap we aimed to characterize the microstructural damage pattern, and its relationship with cognitive profile, in treatment-seeking AUD patients. Twenty-two AUD patients and 18 healthy controls underwent a multimodal MRI protocol including diffusion tensor imaging (DTI), alongside a comprehensive neurocognitive assessment. We used a principal component analysis (PCA) to identify superordinate components maximally explaining variability in cognitive performance, and whole-brain voxelwise analyses to unveil the neural correlates of AUD patients' cognitive impairment in terms of different white-matter microstructural features, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). PCA revealed a basic executive component, significantly impaired in AUD patients, associated with tasks tapping visuo-motor processing speed, attention and working-memory. Within a widespread pattern of white-matter damage in patients, we found diverse types of relationship linking WM microstructure and executive performance: (i) in the whole sample, we observed a linear relationship involving MD/RD metrics within both 'superficial' white-matter systems mediating connectivity within large-scale brain networks, and deeper systems modulating their reciprocal connections; (ii) in AUD patients vs. controls, a performance-by-group interaction highlighted a MD/AD pattern involving two frontal white-matter systems, including the genu of corpus callosum and cingulum bundle, mediating structural connectivity among central executive, salience and default mode networks. Alterations of prefrontal white-matter pathways are suggestive of abnormal structural connectivity in AUD, whereby a defective interplay among large-scale networks underpins patients' executive dysfunction. These findings highlight different directions for future basic and translational research aiming to tailor novel rehabilitation strategies and assess their functional outcomes.
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Alcoholismo/patología , Alcoholismo/fisiopatología , Disfunción Cognitiva/fisiopatología , Función Ejecutiva/fisiología , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Neuroimagen , Desempeño Psicomotor/fisiología , Sustancia Blanca/patología , Adulto , Alcoholismo/complicaciones , Alcoholismo/diagnóstico por imagen , Atención/fisiología , Disfunción Cognitiva/etiología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Neuroimagen/métodos , Sustancia Blanca/diagnóstico por imagenRESUMEN
The neural bases of cognitive impairment(s) in alcohol use disorders (AUDs) have been explained either with the specific involvement of frontal regions mostly affected by alcohol neurotoxic effects, or with a global brain damage underlying different neuro-cognitive alterations. Novel insights into this issue might come from the analysis of resting-state brain activity, representing a baseline level of intrinsic connectivity within and between the networks underlying cognitive performance. We thus addressed the neural bases of cognitive impairment(s) in 22 AUD patients, compared with 18 healthy controls, by coupling resting-state fMRI with an in-depth neuropsychological assessment of the main cognitive domains. We assessed a relationship between AUD patients' cognitive impairment and two complementary facets of intrinsic brain functioning, i.e., intensity of activation and functional network connectivity, related to the strength of connectivity within and between resting-state networks, respectively. Alcoholic patients' decreased cognitive performance involved specifically an executive domain associated with attentional and working-memory tasks. This impairment reflected an abnormal relationship, in patients versus controls, between cognitive performance and the intensity of intrinsic activity in the dorsolateral prefrontal and striatal nodes of the executive control network. Functional connectivity between the same structures was positively correlated with executive performance in the whole sample, but significantly reduced in patients. The present data suggest that AUD patients' executive impairment reflects dysfunctional connectivity between the cortical and subcortical nodes of the networks underlying cognitive control on goal-directed behavior. This evidence provides a baseline for future studies addressing the abnormal neural architecture underlying cognitive impairment in AUDs and the outcome of rehabilitative treatment.