Exploring the administrative burden faced by hematologists: a comprehensive study in Italy.

Background: Administrative burdens have been identified as a major issue impacting patient care, professional practice, and the overall efficiency of healthcare systems. The aim of this study is to assess the administrative burden faced by Italian hematologists. Methods: A cross-sectional survey that included both closed-ended quantitative questions and open-ended free text answer options was administered to 1,570 hematologists working with malignancies and members of Italian GIMEMA Foundation - Franco Mandelli ONLUS and the Italian Linfomi Foundation (FIL). The survey was conducted online from May 24 to June 30, 2023. Descriptive statistics were computed for the quantitative data to clearly summarize the responses and descriptive analysis of free text responses was carried out. Results: Surveyed hematologists spend an average of 47.07% of their time on administrative tasks, with 63.22% (n = 110) of respondents reporting spending at least half of their time on these activities. More than half (57.47%, n = 100) reported that "Patient care" is the medical task most affected by a lack of time. Additionally, 55.17% (n = 96) reported experiencing burnout in the past 6 months, with filling out "Forms" being identified as the top contributing administrative task by 27.59% (n = 48) of respondents, followed by "Scheduling" (24.71%, n = 43) and "Managing IT system failures" (21.84%, n = 38). Nearly half of the surveyed hematologists (45.40%, n  =  = 79) identified patient care as the top priority requiring more time. Conclusions: The study confirms that the administrative workload of hematologists has a significant impact on patient care, communication, and burnout risk, reducing the time available for patient care, leading to exhaustion and concern about clinical errors.

Ecological validity of performance-based cognitive screeners in amyotrophic lateral sclerosis: preliminary evidence.

BACKGROUND: This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes. METHODS: N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview). RESULTS: The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027). DISCUSSION: This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers.

Association of APOE genotype and cerebrospinal fluid Aß and tau biomarkers with cognitive and motor phenotype in amyotrophic lateral sclerosis.

OBJECTIVE: Little is known about amyotrophic lateral sclerosis (ALS)-nonspecific cognitive deficits - most notably memory disturbance - and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aß and tau proteins with cognitive and motor phenotype in ALS. METHODS: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aß42, Aß40, total tau (T-tau), and phosphorylated tau (P-tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype. RESULTS: APOE-E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non-carriers) and lower CSF Aß42 (-0.8 vs. 0.1, log-transformed values) and Aß42/40 ratio (-0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aß42 levels, possibly reflecting cerebral Aß deposition. While lower Aß42/40 correlated with lower memory score (ß = 0.20), Aß42 positively correlated with both ALS-specific (ß = 0.24) and ALS-nonspecific (ß = 0.24) scores. Although Aß42/40 negatively correlated with T-tau (ß = -0.29) and P-tau181 (ß = -0.33), we found an unexpected positive association of Aß42 and Aß40 with both tau proteins. Regarding motor phenotype, lower levels of Aß species were associated with lower motor neuron (LMN) signs (Aß40: ß = 0.34; Aß42: ß = 0.22). CONCLUSIONS: APOE haplotype and CSF Aß biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD-like pathophysiological processes, but additional ALS-specific mechanisms could be involved.

Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach.

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.

Longitudinal Feasibility of the Montreal Cognitive Assessment (MoCA) in Non-Demented ALS Patients.

INTRODUCTION: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M = 6.8; SD = 1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability, and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration, and severity and progression rate). RESULTS: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t[32] = -0.80; p = 0.429) and was reliable at retest (intra-class correlation = 0.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived - with baseline MoCA scores being the only significant predictor of retest performances (ps < 0.001). CONCLUSIONS: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners - such as the ECAS - should be preferred whenever possible.

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients.

BACKGROUND: The present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 88 ALS patients without frontotemporal dementia were assessed for FI-Katz's Basic ADL Scale (BADL) and Lawton-Brody's Instrumental ADL Scale (IADL)-, cognition-Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-and behaviour-Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders-i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King's and Milano-Torino stages. RESULTS: Higher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features-as measured by the Dimensional Apathy Scale (DAS)-were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without. DISCUSSION: Among non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.

Validity, diagnostics and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

BACKGROUND: This study is aimed at assessing the clinimetric properties and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in patients with Huntington's disease (HD). METHODS: N = 39 motor-manifest HD patients, N = 74 Parkinson's disease (PD) patients and N = 92 matched HCs were administered the MoCA. HD patients further underwent the Unified Huntington's Disease Rating Scale (UHDRS), self-report questionnaires for anxiety and depression and a battery of first- and second-level cognitive tests. Construct validity was tested against cognitive and behavioural/psychiatric measures, whereas ecological validity against motor-functional subscales of the UHDRS. Sensitivity to disease severity was tested, via a logistic regression, by exploring whether the MoCA discriminated between patients in Shoulson-Fahn stage ≤ 2 vs. > 2. The same analysis was employed to test its ability to discriminate HD patients from HCs and PD patients. RESULTS: The MoCA converged towards cognitive and behavioural measures but diverged from psychiatric ones, being also associated with motor/functional measures from the UHDRS. In identifying patients with cognitive impairment, adjusted MoCA scores were highly accurate (AUC = .92), yielding optimal diagnostics at the cut-off of < 19.945 (J = .78). The MoCA was able to discriminate patients in the middle-to-advanced from those in the early-to-middle stages of the disease (p = .037), as well as to differentiate HD patients from both HCs (p < .001) and PD patients (p < .001). CONCLUSIONS: The MoCA is a valid, diagnostically sound and feasible cognitive screener in motor-manifest HD patients, whose adoption is thus encouraged in clinical practice and research.

An exploratory study on counterfactual thinking in amyotrophic lateral sclerosis.

Objectives: This study aimed at exploring (1) the motor and non-motor correlates of counterfactual thinking (CFT) abilities in non-demented amyotrophic lateral sclerosis (ALS) patients and (2) the ability of CFT measures to discriminate these patients from healthy controls (HCs) and patients with and without cognitive impairment. Methods: N = 110 ALS patients and N = 51 HCs were administered two CFT tasks, whose sum, resulting in a CFT Index (CFTI), was addressed as the outcome. Patients further underwent an in-depth cognitive, behavioral, and motor-functional evaluation. Correlational analyses were run to explore the correlates of the CFTI in patients. Logistic regressions were performed to test whether the CFTI could discriminate patients from HCs. Results: The CFTI was selectively associated (p ≤ 0.005) with fluency and memory subscales of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), but not with other variables. CFTI scores discriminated patients from HCs (p < 0.001) with high accuracy (82%), but not patients with a normal vs. defective performance on the ECAS-Total. Conclusion: CFT measures in non-demented ALS patients were associated with verbal fluency and memory functions, and they were also able to discriminate them from HCs.

Bulbar involvement and cognitive features in amyotrophic lateral sclerosis: a retrospective study on 347 patients.

Background: This study aimed at clarifying the role of bulbar involvement (BI) as a risk factor for cognitive impairment (CI) in non-demented amyotrophic lateral sclerosis (ALS) patients. Methods: Data on N = 347 patients were retrospectively collected. Cognition was assessed via the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). On the basis of clinical records and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, BI was characterized as follows: (1) BI at onset-from medical history; (2) BI at testing (an ALSFRS-R-Bulbar score ≤11); (3) dysarthria (a score ≤3 on item 1 of the ALSFRS-R); (4) severity of BI (the total score on the ALSFRS-R-Bulbar); and (5) progression rate of BI (computed as 12-ALSFRS-R-Bulbar/disease duration in months). Logistic regressions were run to predict a below- vs. above-cutoff performance on each ECAS measure based on BI-related features while accounting for sex, disease duration, severity and progression rate of respiratory and spinal involvement and ECAS response modality. Results: No predictors yielded significance either on the ECAS-Total and -ALS-non-specific or on ECAS-Language/-Fluency or -Visuospatial subscales. BI at testing predicted a higher probability of an abnormal performance on the ECAS-ALS-specific (p = 0.035) and ECAS-Executive Functioning (p = 0.018). Lower ALSFRS-R-Bulbar scores were associated with a defective performance on the ECAS-Memory (p = 0.025). No other BI-related features affected other ECAS performances. Discussion: In ALS, the occurrence of BI itself, while neither its specific features nor its presence at onset, might selectively represent a risk factor for executive impairment, whilst its severity might be associated with memory deficits.

Phosphorylated tau in plasma could be a biomarker of lower motor neuron impairment in amyotrophic lateral sclerosis.

INTRODUCTION: Plasma levels of phosphorylated tau (P-tau181) have been recently reported to be increased in amyotrophic lateral sclerosis (ALS) and associated with lower motor neuron (LMN) impairment. PATIENTS AND METHODS: We quantified plasma P-tau181 (pP-tau181) in a cohort of 29 deeply phenotyped ALS patients using the new fully automated Lumipulse assay and analysed phenotype-biomarker correlations. RESULTS: pP-tau181 levels correlated positively with a clinical LMN score (r = 0.3803) and negatively, albeit not significantly, with a composite index of muscle strength (r = - 0.3416; p = 0.0811), but not with Penn Upper Motor Neuron (UMN) Score. Accordingly, pP-tau181 correlated with electromyographic indices of spinal active and chronic denervation (r = 0.4507 and r = 0.3864, respectively) but not with transcranial magnetic stimulation parameters of UMN dysfunction. pP-tau181 levels did not correlate with those in the cerebrospinal fluid (CSF), serum NFL, serum GFAP, CSF/serum albumin ratio, or estimated glomerular filtration rate, but correlated with plasma creatine kinase levels (r = 0.4661). Finally, while not being associated with neuropsychological phenotype, pP-tau181 correlated negatively with pH (r = - 0.5632) and positively with partial pressure of carbon dioxide (PaCO2; r = 0.7092), bicarbonate (sHCO3-; r = 0.6667) and base excess (r = 0.6611) on arterial blood gas analysis. DISCUSSION: pP-tau181 has potential as ALS biomarker and could be associated with LMN impairment. Its raised levels might reflect pathophysiological processes (tau hyperphosphorylation and/or release) occurring in the axons of LMNs distantly from the CNS and the CSF. pP-tau181 could also be associated with respiratory dysfunction.

Single task-level, 2SD-based cutoffs for the Italian version of the Edinburgh Cognitive and Behavioral ALS screen (ECAS).

The present study aimed at deriving, by means of a traditional "2 standard deviation-based" (2SD) approach, single task-level cutoffs for the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Cutoffs were derived - as M-2*SD - from the sample of healthy participants (HPs) included within 2016 Poletti et al.'s normative study - N = 248; 104 males; age: 57.8 ± 10.6; education: 14.1 ± 4.6 - separately for the four, original demographic classes: 1) education <14 years and age ≤60 years; 2) education <14 years and age >60 years; 3) education ≥14 years and age ≤60 years; 4) education ≥14 years and age >60 years. The prevalence of deficits on each task was then estimated within a cohort of N = 377 amyotrophic lateral sclerosis (ALS) patients without dementia. The distribution of abnormal performance prevalences was overall consistent with the cognitive phenotype of ALS. In conclusion, the single task-level cutoffs herewith provided for the Italian version of the ECAS, which complement those already available within Poletti et al.'s normative framework, will help better profile Italian ALS patients' cognitive phenotype within both clinical and research settings.

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.

Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis.

Objective: To investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS. Materials and methods: Serum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs). Results: sNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King's stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR). Interpretation: We confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.

Clinical usability of the Story-Based Empathy Task (SET) in non-demented ALS patients.

BACKGROUND: This study aimed at assessing the clinical usability of the Story-Based Empathy Task (SET) in non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 106 non-demented ALS patients and N = 101 healthy controls (HCs) were administered the SET, which includes three subtests assessing Emotion Attribution (SET-EA), Intention Attribution (SET-IA) and causal inference (SET-CI) - the latter being a control task. Patients also underwent the Reading the Mind in the Eyes Test (RMET), the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and a thorough behavioural and motor-functional evaluation. The diagnostics of the SET-EA and -IA were tested against a defective performance on the RMET. The association between SET subtests and cognitive/behavioural outcomes was examined net of demographic and motor-functional confounders. Case-control discrimination was explored for each SET subtest. RESULTS: Demographically adjusted SET-EA and -IA scores accurately detected defective RMET performances at the optimal cutoffs of <3.04 (AUC = .84) and <3.61 (AUC = .88), respectively. By contrast, the SET-CI performed poorly in doing so (AUC = .58). The SET-EA converged with the RMET, as well as with ECAS-Executive and -Memory scores, whilst the SET-IA was unrelated to cognitive measures (including the RMET); the SET-CI was related to the ECAS-Language the ECAS-Executive. SET subscores were unrelated to behavioural outcomes. Only the SET-EA discriminated patients from HCs. CONCLUSIONS: The SET as a whole should not be addressed as a social-cognitive measure in this population. At variance, its subtest tapping on emotional processing - i.e., the SET-EA - is recommended for use as an estimate of social-cognitive abilities in non-demented ALS patients.

Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.

BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients. METHODS: N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33). RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach. DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.

Relationship between cerebrospinal fluid/serum albumin quotient and phenotype in amyotrophic lateral sclerosis: a retrospective study on 328 patients.

BACKGROUND: We analysed the relationship between cerebrospinal fluid (CSF)/serum albumin quotient (Q-Alb) and phenotype in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: Three hundred twenty-eight single-centre consecutive patients with ALS were evaluated for Q-Alb, basic epidemiological and clinical data, motor phenotype, cognitive/behavioural impairment, clinical staging, clinical and neurophysiological indexes of upper (UMN) and lower motor neuron (LMN) dysfunction, and presence of ALS gene mutations. RESULTS: Q-Alb did not correlate with age but was independently associated with sex, with male patients having higher levels than female ones; the site of onset was not independently associated with Q-Alb. Q-Alb was not associated with motor phenotype, cognitive/behavioural impairment, disease stage, progression rate, survival, or genetic mutations. Among measures of UMN and LMN dysfunction, Q-Alb only had a weak positive correlation with an electromyography-based index of active limb denervation. CONCLUSION: Previous work has documented increased Q-Alb in ALS compared to unaffected individuals. This, together with the absence of associations with nearly all ALS phenotypic features in our cohort, suggests dysfunction of the blood-CSF barrier as a shared, phenotype-independent element in ALS pathophysiology. However, correlation with the active denervation index could point to barrier dysfunction as a local driver of LMN degeneration.

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.