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.

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.

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.

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 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.

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.

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.

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.

Psychomotor speed as a predictor of functional status in older chronic heart failure (CHF) patients attending cardiac rehabilitation.

BACKGROUND: The association among psychological, neuropsychological dysfunctions and functional/clinical variables in Chronic Heart Failure (CHF) has been extensively addressed in literature. However, only a few studies investigated those associations in the older population. PURPOSE: To evaluate the psychological/neuropsychological profile of older CHF patients, to explore the interrelation with clinical/functional variables and to identify potential independent predictors of patients' functional status. METHODS: This study was conducted with a multi-center observational design. The following assessments were performed: anxiety (Hospital Anxiety and Depression Scale, HADS), depression (Geriatric Depression Scale, GDS), cognitive impairment (Addenbrooke's Cognitive Examination Revised, ACE-R), executive functions (Frontal Assessment Battery, FAB), constructive abilities (Clock Drawing Test, CDT), psychomotor speed and alternated attention (Trail Making Test, TMT-A/B), functional status (6-minute walking test, 6MWT) and clinical variables (New York Heart Association, NYHA; Brain Natriuretic Peptide, BNP; left ventricular ejection fraction, LVEF; left ventricular end diastolic diameter, LVEDD; left ventricular end diastolic volume, LVEDV; tricuspid annular plane systolic excursion, TAPSE). RESULTS: 100 CHF patients (mean age: 74.9±7.1 years; mean LVEF: 36.1±13.4) were included in the study. Anxious and depressive symptoms were observed in 16% and 24,5% of patients, respectively. Age was related to TMT-A and CDT (r = 0.49, p<0.001 and r = -0.32, p = 0.001, respectively), Log-BNP was related to ACE-R-Fluency subtest, (r = -0.22, p = 0.034), and 6MWT was related to ACE-R-Memory subtest and TMT-A (r = 0.24, p = 0.031 and r = -0.32, p = 0.005, respectively). Both anxiety and depression symptoms were related to ACE-R-Total score (r = -0.25, p = 0.013 and r = -0.32, p = 0.002, respectively) and depressive symptoms were related to CDT (r = -0.23, p = 0.024). At multiple regression analysis, Log-BNP and TMT-A were significant and independent predictors of functional status: worse findings on Log-BNP and TMT-A were associated with shorter distance walked at the 6MWT. CONCLUSIONS: Psychological and neuropsychological screening, along with the assessment of psychomotor speed (TMT-A), may provide useful information for older CHF patients undergoing cardiac rehabilitation.