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.

Motor, cognitive and behavioural profiles of C9orf72 expansion-related amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) individuals carrying the hexanucleotide repeat expansion (HRE) in the C9orf72 gene (C9Pos) have been described as presenting distinct features compared to the general ALS population (C9Neg). We aim to identify the phenotypic traits more closely associated with the HRE and analyse the role of the repeat length as a modifier factor. METHODS: We studied a cohort of 960 ALS patients (101 familial and 859 sporadic cases). Motor phenotype was determined using the MRC scale, the lower motor neuron score (LMNS) and the Penn upper motor neuron score (PUMNS). Neuropsychological profile was studied using the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Frontal Behavioral Inventory (FBI), the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI). A two-step PCR protocol and Southern blotting were performed to determine the presence and the size of C9orf72 HRE, respectively. RESULTS: C9orf72 HRE was detected in 55/960 ALS patients. C9Pos patients showed a younger onset, higher odds of bulbar onset, increased burden of UMN signs, reduced survival and higher frequency of concurrent dementia. We found an inverse correlation between the HRE length and the performance at ECAS ALS-specific tasks (P = 0.031). Patients also showed higher burden of behavioural disinhibition (P = 1.6 × 10-4), lower degrees of depression (P = 0.015) and anxiety (P = 0.008) compared to C9Neg cases. CONCLUSIONS: Our study provides an extensive characterization of motor, cognitive and behavioural features of C9orf72-related ALS, indicating that the C9orf72 HRE size may represent a modifier of the cognitive phenotype.

Prevalence and determinants of language impairment in non-demented amyotrophic lateral sclerosis patients.

BACKGROUND AND PURPOSE: This study aimed at estimating the prevalence of language impairment (LI) in a large, clinic-based cohort of non-demented amyotrophic lateral sclerosis (ALS) patients and assessing its underpinnings at motor and non-motor levels. METHODS: Non-demented ALS patients (N = 348) underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), as well as an assessment of behavioural/psychiatric and motor-functional features. The prevalence of LI was estimated based on the proportion of patients showing a performance below the age- and education-adjusted cut-off on the ECAS-Language. Multiple regression models were run to assess the determinants of language functioning and impairment. RESULTS: The prevalence of LI was 22.7%. 46.6% of the variance of ECAS-Language scores remained unexplained, with only the ECAS-Executive positively predicting them (p < 0.001; η2  = 0.07). Similarly, only a lower score on the ECAS-Executive predicted a higher probability of a below cut-off ECAS-Language performance (p < 0.001). Spelling and Naming tasks were the major drivers of ECAS-Language performance. CONCLUSIONS: This study suggests that, in non-demented ALS patients, LI occurs in ≈23% of cases, is significantly driven by executive dysfunction but, at the same time, partially independent of it and is not associated with other motor or non-motor features.

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.

Diagnostic properties of the Italian ECAS Carer Interview (ECAS-CI).

BACKGROUND: This study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI). MATERIALS: N = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0-13) and (2) that of individual symptom clusters (SC; range = 0-6). Diagnostics were explored against an FBI score ≥ than the 95th percentile of the patients' distribution. RESULTS: Both the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS. DISCUSSION: The ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: ≥ 3).

Reliable change indices for the Italian Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

This study aimed at providing standardized regression-based (SRB) reliable change indices (RCIs) for the Italian Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Thirty-one consecutive ALS patients undergoing the ECAS were followed-up (T1) at 6.5 ± 1 months (range = 5-8). Ceiling/floor effects, practice effect, and test-retest reliability were assessed. Each ECAS measure was regressed by stepwise-entering as predictors demographics, respective T0 scores, T0 disease duration and ALSFRS-R, retest interval, and progression rate (ΔFS) - i.e., (48 - ALSFRS-RT0)/disease durationT0 in months. Ceiling effects were infrequently detected, no practice effect emerged and all ECAS measures were reliable at retest (except for Language and Visuo-spatial subscales). T0 scores predicted all ECAS measures except for the Visuo-spatial subscale. The availability of RCIs for the Italian ECAS will aid ALS-related clinical practice and research within the longitudinal dimension.

Feasibility and diagnostics of the Frontal Assessment Battery (FAB) in amyotrophic lateral sclerosis.

BACKGROUND: The present study aimed at evaluating the diagnostic properties of the Frontal Assessment Battery (FAB) in non-demented ALS patients by addressing the Edinburgh Cognitive Behavioural ALS Screen (ECAS) as the gold standard, as well as by examining the association between its administrability and scores with motor-functional measures. MATERIALS: N = 348 consecutive patients were administered the ECAS and FAB. Disease severity (ALSFRS-R), duration, progression rate (ΔFS), and stages (via King's and Milano-Torino systems) were considered. Administrability rates and prevalence of below-cut-off FAB scores were compared across clinical stages; regression models allowed to test whether, net of the ECAS-Total, motor features predicted the probability of the FAB not being administrable and of a defective FAB score. Intrinsic and post-test diagnostics were explored against a combined defective ECAS-Executive and ECAS-Fluency scores. RESULTS: 85.3% of patients managed to complete the FAB. FAB administrability rates decreased with advanced clinical stages, whereas the prevalence of below-cut-off FAB scores did not. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and ALSFRS-R-upper-limb scores; no motor features, but the ECAS-Total, predicted a below-cut-off performance on the FAB. Raw and adjusted FAB scores showed high accuracy (AUC = .85 and .81, respectively) and good intrinsic and post-test properties. DISCUSSION: The FAB is featured by optimal diagnostics for detecting executive deficits in ALS, provided that it can be administered according to its original, standardized procedure, and thus that patients have sufficiently spared motor abilities to complete the test.

Diagnostic properties of the Frontal Assessment Battery (FAB) in Huntington's disease.

Background: This study aimed at assessing the diagnostic properties of the Frontal Assessment Battery (FAB) as to its capability to (1) discriminate healthy controls (HCs) from patients with Huntington's disease (HD) and (2) identify cognitive impairment in this population. Materials: Thirty-eight consecutive HD patients were compared to 73 HCs on the FAB. Patients further underwent the Montreal Cognitive Assessment (MoCA) and the Unified Huntington's Disease Rating Scale (UHDRS). Receiver-operating characteristics (ROC) analyses were run to assess both intrinsic-i.e., sensitivity (Se) and specificity (Sp), and post-test diagnostics, positive and negative predictive values (PPV; NPV) and likelihood ratios (LR+; LR-), of the FAB both in a case-control setting and to identify, within the patient cohort, cognitive impairment (operationalized as a below-cut-off MoCA score). In patients, its diagnostic accuracy was also compared to that of the cognitive section of the UHDRS (UHDRS-II). Results: The FAB and UHDRS-II were completed by 100 and 89.5% of patients, respectively. The FAB showed optimal case-control discrimination accuracy (AUC = 0.86-0.88) and diagnostic properties (Se = 0.68-0.74; Sp = 0.88-0.9; PPV = 0.74-0.8; NPV = 0.84-0.87; LR+ = 5.6-7.68; LR- = 0.36-0.29), performing even better (AUC = 0.9-0.91) at identifying cognitive impairment among patients (Se = 0.73-1; Sp = 0.86-0.71; PPV = 0.79-0.71; NPV = 0.82-1; LR+ =5.13-3.5; LR- = 0.31-0) and comparably to the UHDRS-II (89% vs. 85% of accuracy, respectively; p = 0.46). Discussion: In HD patients, the FAB is highly feasible for cognitive screening aims, being also featured by optimal intrinsic/post-test diagnostics within both case-control and case-finding settings.

The Frontal Assessment Battery (FAB) effectively discriminates between MCI and dementia within the clinical spectrum of neurochemically confirmed Alzheimer's disease.

Background: This study aimed at testing the ability of the frontal assessment battery (FAB) to differentiate between patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD), as well as comparing its discriminative power to that of the Mini-Mental State Examination (MMSE). Methods: The present retrospective cohort included N = 107 Aß-positive patients diagnosed with either MCI due to AD (N = 40) or probable AD dementia (ADD; N = 67). A two-step multiple logistic regression (MLR) was run to predict an MCI vs. ADD diagnosis based on FAB scores. Within the baseline step, demographics, disease duration, MMSE scores, and information on cognitive phenotypes were entered, with the FAB being added within the second step. Receiver-operating characteristics analyses were also run to derive intrinsic and post-test diagnostics. Results: Within the baseline MLR step, only lower MMSE scores predicted the occurrence of ADD; by adding the FAB, which likewise was able to discriminate between MCI and ADD (p = 0.016), a significant increase in model fit was detected (p = 0.007). The diagnostic efficiency of the FAB (AUC = 0.85) was comparable (p = 0.583) to that of the MMSE (AUC = 0.82), also yielding good intrinsic and post-test diagnostics, which were comparable to those of the MMSE. Discussion: The FAB is a diagnostically sound screener to discriminate between MCI and ADD, independently of patients' overall cognitive profile. In doing so, the FAB is comparable to the MMSE, and the complementation of the latter with the former is advisable in order to increase the accuracy in differentiating between MCI and ADD within screening sessions.

Validity and diagnostics of the Reading the Mind in the Eyes Test (RMET) in non-demented amyotrophic lateral sclerosis (ALS) patients.

Background: The aim of this study was to explore the construct validity and diagnostic properties of the Reading the Mind in the Eyes Test (RMET) in non-demented patients with amyotrophic lateral sclerosis (ALS). Materials: A total of 61 consecutive patients and 50 healthy controls (HCs) were administered the 36-item RMET. Additionally, patients underwent a comprehensive assessment of social cognition via the Story-Based Empathy Task (SET), which encompasses three subtests targeting Causal Inference, Emotion Attribution (SET-EA), and Intention Attribution (SET-IA), as well as global cognitive [the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and behavioral screening [the Frontal Behavioral Inventory (FBI); the Dimensional Apathy Scale (DAS); the Beck Depression Inventory (BDI); and the State and Trait Anxiety Inventory-Y]. The construct validity of the RMET was tested by regressing it within a stepwise model that encompassed as predictors the abovementioned cognitive and behavioral measures, covarying for demographic and motor confounders. Receiver-operating characteristics (ROC) analyses allowed exploring intrinsic and post-test properties of the RMET both in discriminating patients from HCs and in identifying patients with a defective SET-EA performance. Results: The RMET was solely predicted by the SET-EA (p = 0.003) and SET-IA (p = 0.005). RMET scores showed high accuracy both in discriminating patients from HCs (AUC = 0.81) and in identifying patients with a defective SET-EA score (AUC = 0.82), with adequate-to-optimal both intrinsic and post-test properties. Discussion: The RMET is a convergently and divergently valid measure of affective social cognition in non-demented ALS patients, also featuring optimal intrinsic and post-test diagnostic properties in both case-control and case-finding scenarios.

Semiology and determinants of apathy across neurodegenerative motor disorders: A comparison between amyotrophic lateral sclerosis, Parkinson's and Huntington's disease.

Background: The semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants. Materials: Consecutive ALS (N = 99), PD (N = 73), and HD (N = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression. Function was assessed through disease-specific scales. The DAS was also completed by N = 101 healthy controls (HCs). Between-group comparisons on DAS scores were implemented by covarying for all applicable confounders. Predictive models on DAS scores were built through multiple, stepwise regressions. Results: Parkinson's disease and HD, but not ALS, patients were more apathetic than HCs-with HD patients also selectively showing lower initiation and poorer goal-directed planning than HCs. Higher apathetic features were detected in PD and HD as compared to ALS. Education was a protective factor against apathy in ALS. Anxiety was a risk factor for global apathy in ALS, HD, and to a lesser extent, in PD, whereas, protective only toward affective disintegration in PD and ALS. Cognitive inefficiency was a risk factor toward apathy in both PD and ALS. Depression was a risk factor for executive-related apathy in PD. Discussion: This study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the DAS, in turn informing clinical practice and research.

Diagnostics and clinical usability of the Montreal Cognitive Assessment (MoCA) in amyotrophic lateral sclerosis.

Background: The present study aimed at (1) assessing the diagnostic properties of the Montreal Cognitive Assessment (MoCA) in non-demented ALS patients and at (2) exploring the MoCA administrability according to motor-functional status. Materials: N = 348 patients were administered the MoCA and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Administrability rates and prevalence of defective MoCA scores were compared across King's and Milano-Torino clinical stages. Regression models were run to test whether the non-administrability of the MoCA and a defective score on it were predicted, net of the ECAS-Total, by disease duration, ALS Functional Rating Scale-Revised (ALSFRS-R) and progression rate, computed as (48: ALSFRS-R)/disease duration. Intrinsic and post-test diagnostics were tested against a below-cut-off ECAS-total score. Results: The 79.9% of patients successfully underwent the MoCA, whose administrability rates decreased with advanced clinical stages, at variance with its defective score prevalence. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and-upper-limb scores; no motor features, but the ECAS-Total, predicted a defective MoCA performance. The MoCA showed high accuracy (AUC = 0.82) and good intrinsic and post-test properties-being slightly more specific than sensitive. Discussion: In non-demented ALS patients, the MoCA is featured by optimal diagnostics as a screener for cognitive impairment, especially for ruling-out its occurrence, as long as patients are in the early stages of the disease and have sufficiently spared bulbar and upper-limb functions.

Primary progressive aphasia and motor neuron disease: A review.

Background: This study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-spectrum disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels. Methods: This review was pre-registered (osf.io/ds8m4) and performed in accordance with the 2020 PRISMA guidelines. Case reports/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA/SD. Results: Out of 546 initial records, 56 studies were included. As to case reports/series (N = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) TBK1 mutations represent the most frequent genetic risk factors for PPA-MND.As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%). Discussion: Insights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD spectrum.

Gaze-Contingent Eye-Tracking Training in Brain Disorders: A Systematic Review.

Eye movement abnormalities in association with cognitive and emotional deficits have been described in neurological, neurodevelopmental, and psychiatric disorders. Eye-Tracking (ET) techniques could therefore enhance cognitive interventions by contingently providing feedback to patients. Since no consensus has been reached thus far on this approach, this study aimed at systematically reviewing the current evidence. This review was performed and reported according to PRISMA guidelines. Records were searched for in PubMed, Web of Science, and Scopus (1990-2021) through the following string: ('Eye Tracking' OR 'Eye-Tracking' OR 'Oculomotor') AND ('Neuropsychol*' OR 'Cognitive') AND ('Rehabilitation' OR 'Training' OR 'Stimulation'). Study outcomes were thematically classified and qualitatively synthesized. A structured quality assessment was performed. A total of 24 articles were included, addressing neurodevelopmental (preterm infants and children with autism spectrum disorder, Rett syndrome, or ADHD; N = 14), psychiatric (mood and anxiety disorders or alcohol dependence; N = 7), and neurological conditions (stroke; N = 3). Overall, ET gaze-contingent training proved to be effective in improving cognitive and emotional alterations. However, population heterogeneity limits the generalizability of results. ET gaze-contingent protocols allow researchers to directly and dynamically train attentional functions; together with the recruitment of implicit, "bottom-up" strategies, these protocols are promising and possibly integrable with traditional cognitive approaches.

Upper motor neuron dysfunction is associated with the presence of behavioural impairment in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Increasing evidence shows that approximately half of patients with amyotrophic lateral sclerosis (ALS) display cognitive (ALSci) or behavioural (ALSbi) impairment, or both (ALScbi). The aim of our study was to assess whether the burden of upper and lower motor neuron involvement is associated with the presence of cognitive and behavioural impairment. METHODS: A single-centre retrospective cohort of 110 Italian ALS patients was evaluated to assess correlations between motor and cognitive/behavioural phenotypes. Upper motor neuron regional involvement was measured with the Penn Upper Motor Neuron Score (PUMNS), whilst lower motor neuron signs were assessed using the Lower Motor Neuron Score. The Edinburgh Cognitive and Behavioural ALS Screen-Italian version and the Frontal Behaviour Inventory were administered to evaluate patients' cognitive and behavioural profiles. RESULTS: The PUMNS at first visit was significantly higher in behaviourally impaired ALS patients (ALSbi and ALScbi) compared to behaviourally unimpaired individuals (ALS and ALSci) (9.9 vs. 6.9, p = 0.014). Concerning the different Frontal Behaviour Inventory subdomains, higher PUMNS correlated with the presence of apathy, emotive indifference, inflexibility, inattention, perseveration and aggressiveness. CONCLUSION: To our knowledge, this is the first study showing that a clinical prominent upper motor neuron dysfunction is associated with a more significant behavioural impairment in ALS patients, suggesting the hypothesis of a preferential spreading of the pathology from the motor cortex to the ventromedial prefrontal and orbitofrontal cortex in this group of patients.

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.

Emotional Processing and Experience in Amyotrophic Lateral Sclerosis: A Systematic and Critical Review.

Even though increasing literature describes changes in emotional processing in Amyotrophic Lateral Sclerosis (ALS), efforts to summarize relevant findings are lacking in the field. A systematic literature review was performed to provide a critical and up-to-date account of emotional abilities in ALS. References were identified by searches of PubMed, Web of Science and Scopus (1980-2021, English literature), with the following key terms: ("Amyotrophic Lateral Sclerosis" or "Primary Lateral Sclerosis" or "Motor Neuron") and "Emotion*" and ("Processing" or "Attribution" or "Elaboration" or "Perception" or "Recognition"). Studies concerning only caregivers, pseudobulbar affect, and social cognition were excluded. Forty-one articles were included, all concerning ALS, and seven topics were identified: Emotion recognition, Emotional responsiveness, Emotional reactivity, Faces approachability rating, Valence rating, Memory for emotional materials and Alexithymia. The majority of these aspects have only been sparsely addressed. The evidence confirms altered emotional processing in ALS. The most consistent findings regard the recognition of facial expressions for negative emotions, but also alterations in the subjective responsiveness to emotional stimuli (arousal, valence and approachability), in psychophysiological and cerebral reactivity and in emotional memory, together with alexithymia traits, were reported. According to this evidence, emotional abilities should be included in the clinical assessment and therapeutic interventions.

Association of Clinically Evident Eye Movement Abnormalities With Motor and Cognitive Features in Patients With Motor Neuron Disorders.

BACKGROUND AND OBJECTIVES: Although oculomotor abnormalities (OMAs) are not usually considered prominent features of amyotrophic lateral sclerosis (ALS), they may represent potential clinical markers of neurodegeneration, especially when investigated together with cognitive and behavioral alterations. The aim of our study was to identify patterns of clinically evident OMAs in patients with ALS and to correlate such findings with cognitive-behavioral data. METHODS: Three consecutive inpatient cohorts of Italian patients with ALS and controls were retrospectively evaluated to assess the frequency of OMAs and cognitive-behavioral alterations. The ALS population was divided into a discovery cohort and a replication cohort. Controls included a cohort of cognitively impaired individuals and patients with Alzheimer disease (AD). Participants underwent bedside eye movement evaluation to determine the presence and pattern of OMAs. Cognitive assessment was performed with a standard neuropsychological battery (discovery ALS cohort and AD cohort) and the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS) (replication ALS cohort). RESULTS: We recruited 864 individuals with ALS (635 discovery, 229 replication), 798 who were cognitively unimpaired and 171 with AD. OMAs were detected in 10.5% of our ALS cohort vs 1.6% of cognitively unimpaired controls (p = 1.2 × 10-14) and 11.4% of patients with AD (p = NS). The most frequent deficits were smooth pursuit and saccadic abnormalities. OMA frequency was higher in patients with bulbar onset, prominent upper motor neuron signs, and advanced disease stages. Cognitive dysfunction was significantly more frequent in patients with OMAs in both ALS cohorts (p = 1.1 × 10-25). Furthermore, OMAs significantly correlated with the severity of cognitive impairment and with pathologic scores at the ECAS ALS-specific domains. Last, OMAs could be observed in 35.0% of cognitively impaired patients with ALS vs 11.4% of patients with AD (p = 6.4 × 10-7), suggesting a possible involvement of frontal oculomotor areas in ALS. CONCLUSION: Patients with ALS showed a range of clinically evident OMAs, and these alterations were significantly correlated with cognitive, but not behavioral, changes. OMAs may be a marker of neurodegeneration, and bedside assessment represents a rapid, highly specific tool for detecting cognitive impairment in ALS.

Compensating for verbal-motor deficits in neuropsychological assessment in movement disorders: sensitivity and specificity of the ECAS in Parkinson's and Huntington's diseases.

INTRODUCTION: The study aims at investigating psychometric properties of the Edinburgh cognitive and behavioural ALS screen (ECAS) in Parkinson's (PD) and Huntington's (HD) diseases. The sensitivity and specificity of the ECAS in highlighting HD and PD cognitive-behavioural features and in differentiating between these two populations and from healthy controls (HC) were evaluated. Moreover, correlations between the ECAS and traditional cognitive measures, together with core clinical features, were analysed. METHODS: Seventy-three PD patients, 38 HD patients, and 49 education-matched healthy participants were enrolled. Participants were administered the ECAS, together with other cognitive screening tools and psychological questionnaires. Patients' behavioural assessment was also carried out with carers. RESULTS: The ECAS distinguished between HD patients and HC and between the two clinical syndromes with high sensitivity and specificity. Even if the diagnostic accuracy of the ECAS in distinguishing between PD and HC was low, the PD cognitive phenotype was very well described by the ECAS performances. Convergent validity of the ECAS against other traditional cognitive screening was observed, as well as correlations with psychological aspects and typical clinical features, especially for the HD group. CONCLUSIONS: The ECAS represents a rapid and feasible tool, useful also in other neurodegenerative disorders affecting verbal-motor abilities than the amyotrophic lateral sclerosis such as PD and HD. Clinical applications in these neurodegenerative conditions require further investigations and, probably, some adaptations of the original test.