Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration.

This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy.

Clinimetrics of the cognitive section of the Italian ALS Cognitive Behavioral Screen (ALS-CBS™).

BACKGROUND: The present study aimed at (1) providing further validity and reliability evidence for the Italian version of the cognitive section of the ALS Cognitive Behavioral Screen (ALS-CBS™) and (2) testing its diagnostics within an Italian ALS cohort, as well as at (3) exploring its capability to discriminate patients from healthy controls (HCs). METHODS: N = 293 non-demented ALS patients were administered the cognitive sections of the ALS-CBS™ and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). N = 96 HCs demographically matched with N = 96 patients were also administered the cognitive section of the ALS-CBS™. In patients, factorial and construct validity, internal reliability, and diagnostics against a defective score on the cognitive section of the ECAS were tested. Case-control discrimination was assessed via a logistic regression. RESULTS: ALS-CBS™ cognitive subscales were underpinned by a simple, unidimensional structure, internally reliable (McDonald's ω = 0.74), and mostly related with ECAS executive and fluency scores (rs = 0.54-0.71). Both raw and age- and education-adjusted scores on the cognitive section of the ALS-CBS™ accurately detected ECAS-defined cognitive impairment (AUC = 0.80 and .88, respectively), yielding optimal error-based, information-based and unitary diagnostics. A cut-off of < 15.374 was identified on adjusted scores. The test was able to discriminate patients from HCs (p < 0.001). DISCUSSION: The cognitive section of the Italian ALS-CBS™ is a valid, reliable, and diagnostically sound ALS-specific screener for detecting frontotemporal, executive-/attentive-based cognitive inefficiency in non-demented ALS patients, being also able to discriminate them from normotypical individuals.

Cognitive phenotyping of post-infectious SARS-CoV-2 patients.

BACKGROUND: SARS-CoV-2 infection entails neuroinvasive, neuroinflammatory, and treatment-related features accounting for cognitive deficits in COVID-19-recovered patients. Although screening for such dysfunctions in this population is considered clinically relevant, contributions to cognitive phenotyping including premorbid and disease-related confounders are scarcely represented. This study thus aimed at describing the cognitive outcome at the function-/domain-level of post-infectious SARS-CoV-2 patients being already at risk (RCD +) or not (RCD -) for cognitive decline. METHODS: Fifty-four COVID-19-recovered individuals were classified as either RCD + or RCD - according to medical records. The Mini-Mental State Examination (MMSE), Addebrooke Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Attentive Matrices (AM) were administered (N = 54, 34, 28, and 28 patients, respectively). RESULTS: Prevalence of defective (cutoff = 24.89) MMSE scores was 24.3% in RCD + patients and 5.9% in the RCD - group. ACE-R-total below cutoff scores were less frequent (RCD + : 5.4%; RCD - : 5.9%). Abnormal performances at the FAB an AM were respectively detected in 18.9% and 8.1% of RCD + patients and 0% and 11.8% of the RCD - group. Within the ACE-R subtests, those assessing orientation, attention, and fluency were the most frequently impaired in both groups. Disease-related variables were mostly unassociated with cognitive measures. DISCUSSION: Both RCD + and RCD - COVID-19-recovered individuals might show cognitive deficits within the dysexecutive-inattentive and amnesic spectrum. Non-instrumental, executive/attentive dysfunctions are predominant in this population and can be detected by both screening and domain-specific psychometric tests-although the latter might be more sensitive in RCD - patients.

Cognition and motor phenotypes in ALS: a retrospective study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is phenotypically heterogeneous in motor manifestations, and the extent of upper vs. lower motor neuron involvement is a widespread descriptor. This study aimed to examine cognition across different ALS motor phenotypes. METHODS: ALS patients (N = 124) were classified as classical (N = 66), bulbar (N = 13), predominant-upper motor neuron (PUMN; N = 19), and predominant-lower motor neuron (PLMN; N = 26) phenotypes. Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and function with the ALS Functional Rating Scale-Revised (ALSFRS-R). Revised ALS-FTD consensus criteria were applied for cognitive/behavioral phenotyping. RESULTS: Defective ECAS-total scores were detected in all groups - bulbar: 15.4%, classical: 30.3%, PLMN: 23.1%, and PUMN: 36.8%. Classical and PUMN ALS patients performed worse than PLMN ones on ECAS-total, ALS-specific, Fluency, and Executive measures. No other difference was detected. Worse ASLFRS-R scores correlated with poorer ECAS-total scores in classical ALS patients. CONCLUSIONS: Frontotemporal cognitive deficits are more prevalent in PUMN and classical ALS and linked to disease severity in the latter, but occur also in PLMN phenotypes.

Clinical features and cognitive sequelae in COVID-19: a retrospective study on N=152 patients.

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.

Episodic long-term memory in post-infectious SARS-CoV-2 patients.

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.

Screening for cognitive sequelae of SARS-CoV-2 infection: a comparison between the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA).

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.

The Italian validation of the Communicative Effectiveness Index Questionnaire: a multicentric study.

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.

Validation of the revised classification of cognitive and behavioural impairment in ALS.

OBJECTIVE: In 2017, the diagnostic criteria for cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (ALSFTD-1) have been modified (ALSFTD-2) with the inclusion of a novel category (ALS with combined cognitive and behavioural impairment, ALScbi) and with changes of operational criteria of the other categories (ALS with cognitive impairment (ALSci), ALS with behavioural impairment (ALSbi) and ALS with frontotemporal dementia (ALS-FTD)). We compared the two sets of criteria to assess the effect of the revised criteria on the cognitive classification of patients with ALS. METHODS: Two cohorts of patients with ALS were included in this study: a population-based cohort including patients identified through the Piemonte/Valle d'Aosta register for ALS in the 2014-2017 period (n=321), and a referral cohort recruited at the Turin ALS centre and at the ALS centre of the Maugeri Institute in Milan in the same period (n=205). Cognitive function was classified in blind by two neuropsychologists expert in ALS. RESULTS: ALSFTD-2 criteria determined a shift of about 15% of patients from their original category to a new one. In both cohorts, about 9% of patients were reclassified to the novel category ALScbi. Among patients previously classified as cognitively normal, 14 (4.3%, population-based cohort) and 19 (9.3%, referral cohort) were reclassified as ALSbi or ALSci. The median survival of the different categories was significantly different with both with sets of criteria. CONCLUSIONS: The new ALSFTD-2 criteria, compared with the old ones, have positive effects on the clinical practice being more sensitive to the early cognitive impairment and having a better prognostic yield.

Genetic counselling in ALS: facts, uncertainties and clinical suggestions.

The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.

The Italian McGill Quality of Life Questionnaire-Revised (MQoL-R): Psychometrics in Neurological and Neoplastic Populations.

BACKGROUND: The McGill Quality of Life Questionnaire-Revised (MQoL-R) is the gold standard for assessing QoL in end-of-life, chronic patients; however, an Italian standardization is lacking. OBJECTIVE: This study aimed at assessing the psychometric properties of the Italian MQoL-R in patients with chronic neurological/oncological conditions. METHODS: 177 inpatients with life-threatening, chronic neurological/oncological conditions were consecutively recruited in 8 clinics in Northern/Southern Italy were administered the MQoL-R and the Karnofsky Performance Status (KPS). Factorial structure (Confirmatory Factor Analysis, CFA), reliability (Cronbach's α) and construct validity against the KPS (Pearson's coefficients) were examined. RESULTS: The four-factor model (Physical, Psychological, Existential and Social subscales) was met (comparative fit index = .93; root mean square error of approximation = .07), with all items significantly loading on respective subscales. Internal consistency was good for both the whole scale (Cronbach's α = .83) and subscales (range = .6-.85). The KPS was unrelated to MQoL-R measures, except for the Physical subscale (r = .24). CONCLUSIONS: The Italian MQoL-R is a valid and reliable tool to assess QoL in end-of-life, both neoplastic and neurological, chronic inpatients undergoing palliative care, whose adoption is thus encouraged in both clinical practice and research addressed to such populations.

Equating norms between the ALS Cognitive Behavioral Screen (ALS-CBS™) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in non-demented ALS patients.

BACKGROUND: The present study aimed at deriving equating norms to estimate scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) based on those on the ALS Cognitive Behavioral Screen (ALS-CBS™) in an Italian cohort of non-demented ALS patients. METHODS: ALS-CBS™ and ECAS scores of 293 ALS patients without frontotemporal dementia were retrospectively retrieved. Concurrent validity of the ALS-CBS™ towards the ECAS was tested by covarying for demographics, disease duration and severity, presence of C9orf72 hexanucleotide repeat expansion and behavioural features. A linear-smoothing equipercentile equating (LSEE) model was employed to derive ALS-CBS™-to-ECAS cross-walks. Gaps in LSEE-based estimation were managed via a linear regression-based equating approach. Equivalence between empirical and derived ECAS scores was tested via a two-one-sided test (TOST) procedure for the dependent sample. RESULTS: The ALS-CBS™ predicted the ECAS (ß = 0.75), accounting for the vast majority of its variance (60% out of an R2 = 0.71). Consistently, a strong, one-to-one linear association between ALS-CBS™ and ECAS scores was detected (r = 0.84; R2 = 0.73). The LSEE was able to estimate conversions for the full range of the ALS-CBS™, except for raw scores equal to 1 and 6 - for whom a linear equating-based equation was derived. Empirical ECAS scores were equivalent to those derived with both methods. DISCUSSION: Italian practitioners and researchers have been herewith provided with valid, straightforward cross-walks to estimate the ECAS based on ALS-CBS™ scores in non-demented ALS patients. Conversions herewith provided will help avoid cross-sectional/longitudinal inconsistencies in test adoption within research, and possibly clinical, settings.

A verb-naming test accurately detects cognitive changes in ALS.

Verb-naming tests were proposed for detecting cognitive impairment in ALS, although statistical evidence on their clinical usefulness is still lacking. A total of 29 ALS patients and 29 demographic-matched healthy controls (HCs) were administered the Action-Verb-Naming Test (AVNT), a standardized picture-naming task of actions. Patients were also administered the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and classified according to Strong et al. (Amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:153-4) criteria. The AVNT discriminated ALS patients from HCs (p = 0.026) and yielded high accuracy in detecting cognitive impairments among ALS patients (88% of accuracy; sensitivity = 1; specificity = 0.84; PPV = 0.5; NPV = 1; LR+ = 3.83; LR- = 0), as well as a below-cutoff performance on the ECAS (AUC = 0.74). The AVNT was unrelated to other clinical variables, despite being strongly associated with ECAS total, ALS-specific, Language and Executive scores (rs = 0.65-0.75). These findings show that verb naming is an accurate test to detect domain-specific cognitive changes in ALS patients, regardless of their disease phenotype.

Psychiatric symptoms subsequent to COVID-19 and their association with clinical features: A retrospective investigation.

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.

Pallidal functional connectivity changes are associated with disgust recognition in pure motor amyotrophic lateral sclerosis.

In the present study, we aimed to investigate the resting-state functional connectivity (RS-FC) of the globus pallidus (GP) in patients with amyotrophic lateral sclerosis (ALS) compared to healthy controls, and the relationship between RS-FC changes and disgust recognition. Twenty-six pure-motor ALS patients and 52 healthy controls underwent RS functional MRI and a neuropsychological assessment including the Comprehensive Affect Testing System. A seed-based RS-FC analysis was performed between the left and right GP and the rest of the brain and compared between groups. Correlations between RS-FC significant changes and subjects' performance in recognizing disgust were tested. Compared to controls, patients were significantly less able to recognize disgust. In ALS compared to controls, the seed-based analysis showed: reduced RS-FC between bilateral GP and bilateral middle and superior frontal and middle cingulate gyri, and increased RS-FC between bilateral GP and bilateral postcentral, supramarginal and superior temporal gyri and Rolandic operculum. Decreased RS-FC was further observed between left GP and left middle and inferior temporal gyri and bilateral caudate; and increased RS-FC was also shown between right GP and left lingual and fusiform gyri. In patients and controls, lower performance in recognizing disgust correlated with reduced RS-FC between left GP and left middle and inferior temporal gyri. In pure-motor ALS patients, we demonstrated altered RS-FC between GP and the rest of the brain. The reduced left pallidum-temporo-striatal RS-FC may have a role in the lower ability of patients in recognizing disgust.

The diagnostic value of the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

Objectives: The diagnostic capabilities of specific cognitive screeners are clinically crucial for an early detection of frontotemporal features in amyotrophic lateral sclerosis (ALS) patients. This study aimed at providing diagnostic properties of the cognitive section of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) in Italian ALS patients.Methods: Eighty-nine consecutive Italian ALS patients were classified according to Strong et al. (2017) criteria with a comprehensive neuropsychological assessment. The Italian version of ECAS was also administered, and its accuracy, sensitivity (SE), specificity (SP), negative and positive predictive values (PPV; NPV) and likelihood ratios (LR+; LR-) were computed against clinical diagnoses.Results: The ECAS and its subscales yielded moderate-to-high accuracy (AUC = .7-.87). High SP was overall found (81.8%-100%). The most sensitive measures were ALS-specific and Executive (73.9-78.3%) subscales, while the least were the ALS-non-specific subscales (8.7-17.4%). ECAS measures showed good PPVs (60%-100%) and NPVs (75.9%-91.5%). Acceptable LRs were found (LR+: 6.97-4.3; LR-: .29-.91), with total and ALS-specific measures yielding the best estimates.Conclusions: This is the first study demonstrating the diagnostic value of the ECAS against a thorough neuropsychological assessment in Italy. ECAS-total and -ALS-specific scores are diagnostically sound as to both intrinsic and post-test features, whereas ALS-non-specific measures perform slightly worse.

Italian adaptation of the Beaumont Behavioral Inventory (BBI): psychometric properties and clinical usability.

Objective. Up to 50% of patients affected by amyotrophic lateral sclerosis (ALS) show behavioral changes within the spectrum of frontotemporal degeneration (FTD). Behavioral dysfunctions in ALS patients negatively impact on management, prognosis and survival. It is, thus, crucial to develop ALS-specific psychometric tools for early detecting alterations in behavior. This study aimed at investigating psychometric properties and feasibility of the Beaumont Behavioral Impairment (BBI), a proxy-report questionnaire designed to screen for FTD-like behavioral symptoms in ALS patients.Methods. Ninety ALS patients were compared to 100 healthy participants (HPs) on the BBI. ALS patients underwent clinical, cognitive, mood/anxiety and further behavioral (Frontal System Behavior Scale, FrSBe; Frontal Behavioral Inventory, FBI) evaluation. Validity, reliability, sensitivity and specificity of the BBI were assessed.Results. The BBI was significantly related to FrSBe and FBI scores, whereas not to other measures. A Principal Component Analysis yielded a mono-component structure; Cronbach's α was .93. The BBI proved to be sensitive to changes in behavior as well as to discriminate between different degrees of dysfunction. By addressing the FrSBe as the gold standard, the BBI reached optimal sensitivity (85.7%) and specificity (79.7%) at a cutoff of 10.5. Moreover, the BBI proved to be more accurate than the FrSBe and the FBI in clinical classifications.Conclusion. The BBI showed high internal consistency, as well as good construct, convergent and divergent validity. Its clinical usability is encouraged in ALS patients as being able to sensitively and specifically detect FTD-like behavioral changes.

Standardization of the Italian ALS-CBS™ Caregiver Behavioral Questionnaire.

Background: The present investigation aimed at testing the psychometrics and diagnostics of the Italian version of the Caregiver Behavioral Questionnaire (CBQ) from the ALS Cognitive Behavioral Screen (ALS-CBS™), as well as its case-control discrimination, in a cohort of non-demented patients with ALS. Methods: The caregivers of N = 265 non-demented patients with ALS and N = 99 healthy controls (HCs) were administered the CBQ and the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). For N = 98 patients, an in-depth behavioural/psychopathological assessment via the Frontal Behavioural Inventory (FBI), the Dimensional Apathy Scale (DAS), the State and Trait Anxiety Inventory-Form Y (STAI-Y), and the Beck Depression Inventory (BDI) was also available. Factorial and construct validity, internal reliability, and diagnostics against an abnormal ECAS-CI score were tested in patients. Case-control discrimination was explored through logistic regression. Results: The CBQ was internally reliable (McDonald's ω = 0.90) and underpinned by a simple, unidimensional structure; it converged with ECAS-CI, FBI, and DAS scores and diverged from STAI-Y and BDI ones. A cutoff of ≤ 33 accurately detected abnormal ECAS-CI scores (AUC = 0.85), yielding optimal error- and information-based diagnostics. The CBQ was independent of demographic and disease-related variables and discriminated patients from HCs (p < 0.001). Discussion: The Italian version of the CBQ from the ALS-CBS™ is a valid, reliable, diagnostically sound, and feasible screener for detecting frontotemporal-like behavioural changes in non-demented patients with ALS. Its adoption is thus recommended within clinical practice and research in the view of providing preliminary information on whether the administration of more extensive behavioural instruments is needed.