Search

Background: Spatial navigation deficits are reported as early symptoms of Alzheimer's disease (AD) alongside episodic memory ones. The aim of the present study was to ascertain whether neuropsychological deficits of visuospatial long-term memory can predict behavioral alterations during the navigation of older adults in novel urban environments along the normal aging-dementia continuum of the Alzheimer's type. Methods: A total of 24 community-dwelling patients with Mild Cognitive Impairment (MCI) due to AD, 27 individuals with subjective cognitive decline (SCD), and 21 healthy controls were assessed in terms of their sequential egocentric and allocentric navigation abilities by using a modified version of the Detour Navigation Test, and neuropsychologically tested by the Corsi learning suvra-span (CLSS) test. Generalized linear models were adopted to verify whether the scores obtained by the three groups in the CLSS test predicted wrong turns and moments of hesitation during the navigation task, with the results presented as topographical disorientation scores. Results: Higher scores in the CLSS test predicted fewer wrong turns (b = -0.05; z = -2.91; p = 0.004; net of between-groups differences) and moments of hesitation for patients with MCI due to AD (b = -0.14; z = -2.43; p = 0.015), and individuals with SCD (b = -0.17; z = -3.85; p < 0.001). Conclusions: Since the CLSS test has been reported to be a reliable measure of ecological navigational abilities in the progression towards AD dementia, we recommend its use in clinical practice and highlight implications for future research.

Ad-hoc forensic instruments have been developed for the contemporaneous or retrospective evaluation of testamentary capacity, among which the Testament Definition Scale (TDS), a short rating scale designed to evaluate and quantify the individual’s capacity to give an exhaustive definition of what a testament is. The aim of the study was to derive Italian normative values for the TDS in an adult sample and to provide preliminary evidence for its usability in neurological patients with cognitive decline. The TDS was administered to 341 healthy subjects of different ages (range= 30–92 years) and educational levels (range= 1–20 years), along with the Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB), and to 6 adults with neurodegenerative diseases. In healthy subjects, TDS scores were associated with MoCA and FAB scores;; education was the only significant predictor of TDS scores. In patients with neurodegenerative diseases, TDS scores can dissociate from MoCA and FAB scores. Normative data (cutoff and equivalent scores) for favoring the adoption of the TDS in the assessment of testamentary capacity are here provided.

Large-scale self-supervised pretraining of deep learning models is known to be critical in several fields, such as language processing, where its has led to significant breakthroughs. Indeed, it is often more impactful than architectural designs. However, the use of self-supervised pretraining lags behind in several domains, such as hyperspectral images, due to data scarcity. This paper addresses the challenge of data scarcity in the development of methods for spatial super-resolution of hyperspectral images (HSI-SR). We show that state-of-the-art HSI-SR methods are severely bottlenecked by the small paired datasets that are publicly available, also leading to unreliable assessment of the architectural merits of the models. We propose to capitalize on the abundance of high resolution (HR) RGB images to develop a self-supervised pretraining approach that significantly improves the quality of HSI-SR models. In particular, we leverage advances in spectral reconstruction methods to create a vast dataset with high spatial resolution and plausible spectra from RGB images, to be used for pretraining HSI-SR methods. Experimental results, conducted across multiple datasets, report large gains for state-of-the-art HSI-SR methods when pretrained according to the proposed procedure, and also highlight the unreliability of ranking methods when training on small datasets.

Evidence shows the role men can have to contribute to the prevention of non-consensual relationships and gender violence, mainly fostering educational and social strategies which strengthen egalitarian male models that take consent as a key aspect in their sexual and affective relationships. In this regard, social networks show the existence of discourses that reinforce these male models. However, there is a gap in the analysis of how the previously mentioned discourses on consent are linked to men's sexual satisfaction. The present study deepened into this reality by analysing messages on Reddit and Twitter. Drawing on the Social Media Analytics (SMA) technique, conducted in the framework of the European large-scale project ALL-INTERACT from the H2020 program, the hashtags notallmen and consent were explored aimed at identifying the connections between masculinities and consent. Furthermore, three daily life stories were performed with heterosexual men. Findings shed light on the relevant positioning of men about consent as a key message to eradicate gender-based violence; in parallel, they reveal the existence of New Alternative Masculinities that have never had any relationship without consent: they only get excited by free, mutual and committed consent, while repulsing unconsented or one-sided relationships.

In the original version of this article, some typos regarding the adjustment coefficients for raw MoCA-Visuo-spatial (MoCA-VS) and MoCA-Attention (MoCA-A) scores (Table 3) were present and have now been amended (amended MoCA-VS cell: age=35, education=8; amended MoCA-A cells: age=55, education=8; age=35, education=13). Moreover, some imprecisions regarding the discussion of the discrepancies between the present and previous normative studies have been amended (page 379, Discussion: "More specifically, ESs allotments here reported proved to be stricter than those of Santangelo et al.’s [1] with regard to MoCA-total, -VS, -EF and -A, whereas less strict with regard to MoCA-O and Conti et al.’s [2] total"). We are thankful to the Researcher that has drawn our attention on such elements. The updated Table 3 is below: (Table presented.) Adjustment grids according to age and education for MoCA total and subtest raw scores Sub-test Education Age 35 40 45 50 55 60 65 70 75 80 85 90 95 Total 5 0.35 0.52 0.73 1 1.34 1.73 2.2 2.75 3.38 4.1 4.92 5.84 6.86 8 − 1.22 − 1.05 − 0.83 − 0.56 − 0.23 0.17 0.64 1.18 1.81 2.53 3.35 4.27 5.3 11 − 2.28 − 2.11 − 1.89 − 1.62 − 1.29 − 0.89 − 0.43 0.12 0.75 1.47 2.29 3.21 4.24 13 − 2.84 − 2.67 − 2.45 − 2.18 − 1.85 − 1.45 − 0.98 − 0.43 0.2 0.92 1.73 2.65 3.68 16 − 3.53 − 3.36 − 3.14 − 2.87 − 2.54 − 2.14 − 1.67 − 1.13 − 0.5 0.23 1.04 1.96 2.99 18 − 3.92 − 3.75 − 3.53 − 3.26 − 2.93 − 2.53 − 2.07 − 1.52 − 0.89 − 0.17 0.65 1.57 2.6 21 − 4.43 − 4.26 − 4.05 − 3.78 − 3.45 − 3.05 − 2.58 − 2.03 − 1.4 − 0.68 0.14 1.06 2.08 VS 5 − 0.06 0.13 0.2 0.28 0.37 0.47 0.57 0.69 0.81 0.93 1.07 1.21 8 − 0.3 − 0.24 − 0.18 − 0.1 − 0.02 0.07 0.17 0.27 0.38

Motor regions atrophy has been traditionally assumed to account for selective deficits of verb (V) vs. noun (N) processing in amyotrophic lateral sclerosis (ALS) patients via action semantic impairment (Embodied Cognition Theory, ECT). Nonetheless, accounts pertaining to both motor region sensitivity to the morpho-phonological structure of Vs and executive functioning (EF) contribution (task difficulty) have not been evenly endorsed. This study aimed at assessing neurocognitive underpinnings of N and V processing in ALS patients. ALS patients were compared to healthy participants (HPs) on tasks evaluating N and V semantic and post-semantic processing. Effects of semantic motor content (actionality) of Ns and Vs and of argument structure complexity of Vs were assessed. EF measures were put into relation to language tasks in patients. Both groups performed worse in V than in N lexical retrieval. Patients had difficulties in retrieving low-actionality Vs, being also sensitive to both transitive Vs and those with 2 and 3 arguments. Patients differed form HPs on both object- and action-semantic measures. EF measures were highly related to patients’ V-retrieval performance. ECT-framed explanations for N > V discrepancies in ALS patients are inconsistent with the present results. Indeed, ALS patients showed semantic deficits that are not limited to the action domain and retrieved more easily high-actionality Vs. N > V discrepancies in ALS patients would thus reflect a magnification of a differential processing demand for Vs and Ns, which is likely intrinsic to the neurocognitive system. Nonetheless, ALS patients being sensitive to argument structure complexity of Vs might imply motor regions involvement in V post-semantic processing, possibly at the lemma level.

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.

The original article contains an error. The affiliation 5 “Milan Center for Neuroscience (NeuroMI), Milan, Italy” should be remove from the author Nadia Bolognini’s address.

Background: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB). Methods: The t-FAB (ranging 0–12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18–96 years; education range = 4–23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test–retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores. Results: In HPs, t-FAB measures yielded high inter-rater/test–retest reliability (ICC =.78–.94), were internally related (p ≤.005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤.0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds <.001). Education predicted all t-FAB scores (p <.001), whereas age only the t-FAB-M score (p ≤.004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (rs =.43–.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC =.73-.76). Discussion: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice.

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.

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.

Background: Among clinicians and researchers, it is common knowledge that, in ALS, cognitive and behavioral involvement within the spectrum of frontotemporal degenerations (FTDs) begun to be regarded as a fact in the late 1990s of the twentieth century. By contrast, a considerable body of evidence on cognitive/behavioral changes in ALS can be traced in the literature dating from the late nineteenth century. Methods: Worldwide reports on cognitive/behavioral involvement in ALS dating from 1886 to 1981 were retrieved thanks to Biblioteca di Area Medica “Adolfo Ferrate,” Sistema Bibliotecario di Ateneo, University of Pavia, Pavia, Italy and qualitatively synthetized. Results: One-hundred and seventy-four cases of ALS with co-occurring FTD-like cognitive/behavioral changes, described in Europe, America, and Asia, were detected. Neuropsychological phenotypes were consistent with the revised Strong et al.’s consensus criteria. Clinical observations were not infrequently supported by histopathological, post-mortem verifications of extra-motor, cortical/sub-cortical alterations, as well as by in vivo instrumental exams—i.e., assessments of brain morphology/physiology and psychometric testing. In this regard, as earlier as 1907, the notion of motor and cognitive/behavioral features in ALS yielding from the same underlying pathology was acknowledged. Hereditary occurrences of ALS with cognitive/behavioral dysfunctions were reported, as well as familial associations with ALS-unrelated brain disorders. Neuropsychological symptoms often occurred before motor ones. Bulbar involvement was at times acknowledged as a risk factor for cognitive/behavioral changes in ALS. Discussion: Historical observations herewith delivered can be regarded as the antecedents of current knowledge on cognitive/behavioral impairment in the ALS-FTD spectrum.

Study design: Cross-sectional explorative observational study. Title: Sexual satisfaction in people with spinal cord injury and their partners: an explorative study. Objective: To investigate the determinants of sexual satisfaction among individuals with spinal cord injury and relative partners by assuming a bio-psycho-social perspective. Setting: Online survey. Methods: Thirty-eight individuals (22 individuals with SCI and their partners) were provided with an anonymous self-report questionnaire. Bio-psycho-social dimensions were investigated by using the Barthel Modified Index, Beck Depression Inventory-II, Short Form Health Survey (SF-36). Sexual attitudes of participants were assessed via the Multidimensional Sexual Self-Concept Questionnaire (Snell, 1993). Results: While no differences were observed between individuals with SCI and their partners, women with SCI were overall more satisfied about their sexual life when compared to men with SCI. Coping strategies promoting self-efficacy and an active role in the sexual issues were predictive of Sexual Satisfaction in the couples of persons with SCI and their partners. No significant contribution was played by physical variables. Conclusion: A tailored-made approach assessing the needs of both individuals with SCI and partners is a key aspect for effective sexual rehabilitation protocols. According to the needs and features of each couple, health professionals should drive individuals with SCI and partners to cope with their sexuality within a bio-psycho-social framework underlying it.

Transcranial Direct Current Stimulation (tDCS) has been employed to modulate visuospatial attentional asymmetries, however, further investigation is needed to characterize tDCS-associated variability in more ecological settings. In the present research, we tested the effects of offline, anodal conventional tDCS (Experiment 1) and HD-tDCS (Experiment 2) delivered over the posterior parietal cortex (PPC) and Frontal Eye Field (FEF) of the right hemisphere in healthy participants. Attentional asymmetries were measured by means of an eye tracking-based, ecological paradigm, that is, a Free Visual Exploration task of naturalistic pictures. Data were analyzed from a spatiotemporal perspective. In Experiment 1, a pre-post linear mixed model (LMM) indicated a leftward attentional shift after PPC tDCS; this effect was not confirmed when the individual baseline performance was considered. In Experiment 2, FEF HD-tDCS was shown to induce a significant leftward shift of gaze position, which emerged after 6 s of picture exploration and lasted for 200 ms. The present results do not allow us to conclude on a clear efficacy of offline conventional tDCS and HD-tDCS in modulating overt visuospatial attention in an ecological setting. Nonetheless, our findings highlight a complex relationship among stimulated area, focality of stimulation, spatiotemporal aspects of deployment of attention, and the role of individual baseline performance in shaping the effects of tDCS.

Background: The Italian telephone-based Mini-Mental State Examination (Itel-MMSE), despite being psychometrically sound, has shown relevant ceiling effects, which may negatively impact the interpretation of its scores. In address to overcome such an issue, this study aimed at providing item-level insights on the Itel-MMSE through Item Response Theory (IRT) analyses. Methods: Five-hundred and sixty-seven healthy Italian adults (227 males, 340 females; mean age: 51 ± 17 years, range 18–96; mean education: 13.31 ± 4.3 years). A two-parameter logistic IRT model was implemented to assess item discrimination and difficulty of the Itel-MMSE. Construct unidimensionality, statistical independence of items, and model and item fit were tested. Informativity levels were also assessed graphically. Results: With respect to the Itel-MMSE total score, ceiling effects were found in 92.7% of participants. Unidimensionality was violated; both model and item fit were poor; a few items showed statistical dependence. Both the whole test and its items proved to be scarcely informative, especially for medium-to-high levels of ability, except for attention and spatial orientation subtests, which consistently yielded the highest discriminative capability. Discussion: The Itel-MMSE appears to be most informative in low-performing healthy individuals. However, the present findings should not lead practitioners to aprioristically equate ceiling effects/low informativity to clinical uselessness. Items assessing attention and, to a lesser extent, spatial orientation appear to be the most informative.

Objective: Little is known about disease-related disclosure (DD) in patients with rheumatic musculoskeletal diseases (RMDs). We aim to investigate DD behaviors and to explore which socio-demographic, clinical and psychological factors play a role in this self-disclosure process among patients with RMDs. Methods: A cross-sectional Italian nationwide study captured DD in RMDs in different contexts (workplace, family, friends, partner, social networks). An ad hoc survey was developed and disseminated by the Patients' Association ALOMAR ODV (Lombard Association for Rheumatic Diseases) between June and July 2020. Patient demographics, clinical data, and questionnaires assessing anxiety, depression, anticipated stigma, patient health engagement, perceived social support, and perceived general health status were collected. Results: There were 376 rheumatic patients who completed the survey. There were 73.9% of the participants who talk to others about their RMD “sometimes”; 18.7% disclose their RMD “always/very often”, while 7.4% “never” talk about their RMD. A significant association was detected between DD and both perceived visibility (P =.04) and psychological support (P =.01). Moreover, participants who never/sometimes disclose their RMD reported significantly lower scores in the “Total” Social Support (P <.01) and in the “Friends” subscale (P <.001) compared to others. Psychological support and the “Friends” subscale were the only significant predictors of DD (both P =.002). Conclusions: The majority of RMD patients disclosed their disease “sometimes”. The DD behavior is not associated with any specific demographic or clinical variables. Further research on the subject might help to foster better DD decision-making processes for rheumatic patients in different contexts of daily life.

Background: Sub-clinical cognitive efficiency deficits of a dysexecutive nature are moderately prevalent in healthy older adults and negatively affect their functional outcomes. To screen for such dysfunctions, the Frontal Assessment Battery (FAB) provided promising evidence, although its diagnostic properties have not been tested to date. This study thus aimed at exploring the performance on the FAB of a large sample of Italian healthy adults and comparing it in individuals aged < 75 years vs. ≥ 75 years. Methods: Four hundred and seventy-five healthy adults (169 males, 306 females, age: 61.1 ± 15.1; education 11.7 ± 4.6) were administered the FAB and the Montreal Cognitive Assessment (MoCA). Sensitivity, specificity, positive and negative predictive values and likelihood ratios were computed through receiver-operating characteristics analyses by addressing an above- vs. below-cutoff performance on the MoCA as the state variable (as including measures of executive functioning). Results: The FAB overall showed good accuracy (AUC = 0.71–0.76), although higher for healthy older adults. A trend towards higher specificity (64.4–80.3%) than sensitivity (61.1–77.8%) was found, despite these metrics being comparable in healthy older adults. Negative predictive values (0.98–0.99) were systematically higher than positive predictive values (0.05–0.24), whereas consistent post-test probabilities were detected (positive likelihood ratios: 2.19–3.35; negative likelihood ratios: 0.28–0.48). Discussion: The FAB is an accurate test for the first-level assessment of dysexecutive-related global cognitive inefficiency in the general population, despite being moderately conservative as far as both its pre- and post-test features are concerned. Its diagnostic value is more informative for individuals aged ≥ 75 years.

Background: Patients suffering from stroke in the acute/post-acute phases often present with depressive mood — which negatively impacts on patients’ prognosis. However, psychometric evaluation of mood in acute stroke patients may be challenging due to cognitive deficits. Tools investigating emotional states via a vertical analogue line may overcome language/visuo-spatial disorders. This study thus aimed at (a) investigating the clinical usability of a Visual Analogue Mood Scale (VAMS) in acute stroke patients and (b) investigating the interplay between mood and cognition in this population. Methods: Forty-one acute stroke patients were compared to 41 age-, education- and sex-matched healthy participants (HPs) on the VAMS and on cognitive measures (mental performance in acute stroke, MEPS). A control line bisection (LB) task was administered to control for potential visuo-spatial deficits in patients. Results: Patients reported higher depression levels than HPs (lower VAMS scores); this between-group difference stayed significant when covarying for LB scores. MEPS scores discriminated patients from HPs; among cognitive measures, only the Clock drawing test (CDT) was positively associated with VAMS scores. Lesion side did not affect patients’ mood state; however, disease duration was inversely related to VAMS scores. Discussion: The VAMS proved to be a suitable tool for assessing mood in acute stroke patients, as being independent from post-stroke cognitive sequelae. The CDT might represent an adequate measure of depression-induced, post-stroke cognitive efficiency decrease. Mood disorders might occur and thus should be adequately addressed also in post-acute phases — likely due to longer hospitalization times and regression of anosognosic features.

Background: Norming neuropsychological tests and standardizing their raw scores are needed to draw objective clinical judgments on clients’ neuropsychological profile. The Equivalent Score (ES) method is a regression-based normative/standardization technique that relies on the non-parametric identification of the observations corresponding to the outer and inner tolerance limits (oTL; iTL) — to derive a cut-off, as well as to between-ES thresholds — to mark the passage across different levels of ability. However, identifying these observations is still a time-consuming, “manual” procedure. This work aimed at providing practitioners with a user-friendly code that helps compute TLs and ES thresholds. Methods: R language and RStudio environment were adopted. A function for identifying the observations corresponding to both TLs by exploiting Beta distribution features was implemented. A code for identifying the observations corresponding to ES thresholds according to a z-deviate-based approach is also provided. Results: An exhaustive paradigm of usage of both the aforementioned function and script has been carried out. A user-friendly, online applet is provided for the calculation of both TLs and ESs thresholds. A brief summary of the regression-based procedure preceding the identification of TLs and ESs threshold is also given (along with an R script implementing these steps). Discussion: The present work provides with a software solution to the calculation of TLs and ES thresholds for norming/standardizing neuropsychological tests. These software can help reduce both the subjectivity and the error rate when applying the ES method, as well as simplify and expedite its implementation.

Background: Working memory (WM) abilities are frequently impaired in neurological disorders affecting fronto-parietal cortical/sub-cortical structures. WM deficits negatively influence interventional outcomes and everyday functioning. This study thus aimed at the following: (a) developing and standardizing an ecologically valid task for WM assessment (Ice Cream Test, ICT); (b) validating and norming a novel WM test (Digit Ordering Test, DOT), as well as providing updated norms for digit span (DS) tasks, in an Italian population sample; (c) introducing a novel scoring procedure for measuring WM. Methods: One-hundred and sixty-eight Italian healthy participants—73 male, 95 females; age: 48.4 ± 19.1 (18–86); education: 12.1 ± 4.8 (4–21)—underwent a thorough WM assessment—DOT, ICT, and both forward and backward DS tasks (FDS, BDS). The ICT requires participants to act as waiters who have to keep track of customers’ orders. For each task, WM and total (T) outcomes were computed, i.e., the number of elements in the longest sequence and that of recalled sequences, respectively. Norms were derived via the equivalent score (ES) method. Results: DS ratios (DSRs) were computed for both WM/S and T outcomes on raw DS measures (BDS divided by FDS). Age and education significantly predicted all WM tasks; sex affected FDS and DSR-T scores (males > females). WM measures were highly internally related. Discussion: The present work provides Italian practitioners with a normatively updated, multi-component, adaptive battery for WM assessment (WoMAB) as well as with novel outcomes which capture different WM facets—WM capacity and attentive monitoring abilities.

Background. Motor neuron disease (MND) patients can show oral language deficits mimicking those of frontotemporal degeneration (FTD). Although dysgraphic features have also been reported within the MND-FTD continuum, their characteristics and clinical relevance are still largely unexplored. Aims. Profiling writing disorders in MND patients can help further define their cognitive semiology and thus convey relevant clinical entailments. Therefore, this study aimed at reviewing evidence of writing impairment in MND patients. This review was implemented and reported by consulting Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Qualitative/quantitative measures of writing abilities in MND patients were the primary outcome. Both group studies and case reports/series were taken into consideration. Twenty contributions were included out of an initial N = 83. Potential biases in generalizing results were qualitatively controlled for by extracting background, disease-related, neuropsychological, and neuroanatomofunctional secondary outcomes. Main Contribution. Fifteen studies assessed writing abilities in Japanese patients, whereas the remaining eight in western patients. Central dysgraphic features were reported in both neuropsychologically impaired and unimpaired MND patients. Non-phonologically plausible and morpho-syntactic errors were frequently reported. Although FTD was frequently co-occurent, neither cognitive nor language impairment fully accounted for writing impairment in some patients. By contrast, evidence of peripheral dysgraphia was scarce. Patients displaying writing deficits often presented with bulbar signs and perisylvian cortex involvement (including Exner’s area and the left angular gyrus). Writing deficits proved to be associated with abnormalities in executive functioning and its neural substrates. Writing-to-dictation tasks as well as writing samples assessment proved to be useful to detect writing errors. Conclusion

Up to 35–40% of patients with amyotrophic lateral sclerosis (ALS) present with language deficits falling within the spectrum of frontotemporal lobar degeneration (FTLD). It is currently debated whether frontotemporal involvement occurs or not in motor neuron disease (MND) phenotypes that differ from classical ALS (i.e., both different-from-ALS MNDs and non-classical ALS endo-phenotypes)–this stance being supported by the notion of a common pathology underlying MNDs. To investigate whether language dysfunctions also occur in patients with different-from-classical-ALS adult-onset MNDs can; a) help determine whether the MND-FTLD continuum could be broadened at a neuropsychological level; b) convey relevant entailments to cognitive diagnostics in these populations. The present study thus aimed at reviewing evidence regarding language impairment in different-from-classical-ALS MND patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were consulted to implement and report the present review. Studies were included if a) language was quantitatively assessed b) in patients diagnosed with different-from-classical-ALS MND phenotypes. Studies assessing demented patients only were excluded. From an original N = 1117 contributions, N = 20 group studies were finally included. Secondary outcomes were taken into account for qualitatively assessing potential biases in generalizing results. Studies were divided into those assessing predominant/pure-upper vs. -lower MND patients (UMND/LMND). Language dysfunctions appeared to be more prevalent and severe in UMND patients. Language screeners were able to detect language deficits in both groups. Lexical-semantic deficits appeared to be highly prevalent in both groups and a selective difficulty in action- vs. object-naming was not infrequently detected. Morpho-syntactic deficits were seldom reported in both groups. Phonological deficits and central dysgraphic features were found in UMND patients

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).

Background: The cerebrospinal fluid (CSF)/serum albumin quotient (Q-Alb) is a marker of the blood-CSF barrier (BCSFB) and possibly of the blood–brain barrier (BBB). The latter is known to be altered in Alzheimer’s disease (AD) based on neuropathological and neuroimaging studies. Following investigations performed on clinically diagnosed cohorts, we aimed at comparing Q-Alb in cognitively impaired patients with neurochemical demonstration of AD pathophysiology and neurological disease controls (NDCs). Methods: We evaluated N = 144 AD patients (MCI, N = 43; AD dementia — ADD, N = 101) and N = 132 NDCs. AD patients were all A + according to the A/T/N framework and were neurochemically classified based on T and N parameters. Results: Q-Alb did not significantly differ between AD patients and NDCs. Moreover, it was not associated with disease stage (MCI vs. ADD), MMSE score, or CSF AD biomarkers. Discussion: Our study indicates that BCSFB dysfunction is not a specific feature of AD. When interpreting Q-Alb as a marker of the BBB, the lack of difference from NDCs might be due to BBB dysfunction widely occurring in other neurological, non-degenerative, conditions or — more probably — to low sensitivity of this biochemical parameter towards subtle BBB alterations causing leakage of molecules smaller than albumin. Furthermore, Q-Alb is not associated with the degree of global cognitive deterioration in AD, nor with CSF AD neurochemical biomarkers.

In individui con disturbi cerebrali sospetti o confermati, lo screening cognitivo tramite test performance-based convoglia informazioni di rilievo sia in termini diagnostici e prognostici che in ambito interventistico. Inoltre, tali test vengono spesso impiegati come misure di outcome nell’ambito di studi clinici aventi come oggetto la cognizione. Pertanto, gli screener cognitivi devono possedere solide caratteristiche statistiche e di usabilità. Tuttavia, nel panorama Italiano, gli screener cognitivi non sempre possiedono tali caratteristiche. Inoltre, in Italia, le pratiche di screening cognitivo da remoto sono state storicamente poco considerate, nonostante si prestino facilmente ad essere erogate a distanza tramite media di facile impiego, come il telefono. Tuttavia, avendo il potenziale di abbattere barriere geografiche, logistiche, socio-demografiche ed economiche, la disponibilità di screener cognitivi telefonici implicherebbe rilevanti vantaggi sia in ambito clinico che per l’implementazione e la portata a termine di studi clinici. In ragione di quanto suddetto, nelle prime due Sezioni della presente Dissertazione, in seguito ad una panoramica generale dei principi sottesi alle procedure di screening, viene fornita un’esauriente cornice per lo studio statistico degli screener cognitivi – affrontando 1) le loro applicazioni a fini di screening di popolazione e di case-finding nella pratica e ricerca cliniche, nonché le questioni relative a 2) proprietà clinimetriche (i.e., caratteristiche psicometriche e diagnostiche), 3) taratura (con un focus sul metodo dei Punteggi Equivalenti) e 4) usabilità trasversale/longitudinale. Inoltre, la Sezione 2 riporta una discussione dettagliata e critica 1) sul razionale, 2) su vantaggi e svantaggi e 3) sulle applicazioni cliniche/di ricerca degli screener cognitivi telefonici – focalizzandosi anche 4) sugli aspetti statistici relativi alla loro standardizzazione. Nella terza Sezione, in seguito ad una sinossi aggiornat, In individuals with suspected or confirmed brain disorders, cognitive screening via performance-based tests conveys pivotal information both towards diagnosis and prognosis and within interventional settings. Moreover, such tests are often employed as outcomes measures within clinical studies addressing cognition. Hence, cognitive screeners need to come with sound statistical and feasibility features. However, within the Italian scenario, cognitive screeners do not always present with such characteristics. Moreover, remote cognitive screening procedures have been historically underdeveloped in Italy, despite easily lending themselves to be delivered from a distance via practicable media, such as the telephone. However, by bridging down geographical, logistical, socio-demographic and economic barriers, the availability of telephone-based cognitive screeners would both entail improvements in healthcare settings and ease the implementation and accomplishment of clinical studies. Given the above premises, within the first two Sections of the present Dissertation, after outlining the principles underlying screening procedures in general, a comprehensive, practical framework for the statistical study of cognitive screeners is delivered – addressing 1) their applications for population-screening and case-findings aims within both clinical practice and research, as well as the issues of 2) clinimetrics (i.e., psychometrics and diagnostics), 3) norm derivation (with a focus on the Equivalent Score method) and 4) cross-sectional/longitudinal feasibility. In addition, Section 2 delivers an extensive, critical discussion on the 1) rationale, 2) benefits and shortcomings and 3) clinical/research applications of telephone-based cognitive screeners – also focusing on 4) the statistical issues related to their standardization. Within the third Section, after providing an up-to-date synopsis of the Italian status quo as to the statistical features of both in-person and telephone-bas

Purpose: Several studies investigated prevalence and determinants of physicians’ burnout during the peak of the COVID-19 pandemic, but only a few during the chronic phase of the pandemic. This study thus aimed to examine this topic referring to the “post-COVID-19 era”, defined as a chronic and likely-to-be endemic status quo. Methods: A cross-sectional, online survey (November 2021–January 2022) was addressed to physicians in Lombardia (Northern Italy). Besides socio-demographic and COVID-19-related data, measures of personal, work- and patient-related burnout (Copenhagen Burnout Inventory; CBI), depression (Patient Health Questionnaire-8), anxiety (General Anxiety Disorder-7), and self-efficacy (General Self-Efficacy Scale) were collected. Linear/generalized linear models were run to test associations/predictions of interest. Results: Among the 958 respondents, burnout symptoms were clinically significant in 18.5% of them. Predictive models showed that female sex (OR = 0.73, 95% CI 0.42–1.27), younger age (OR = 0.94, 95% CI 0.59–1.48), shorter job tenure (OR = 1.01, 95% CI 0.62–1.65), trainee status (OR = 1.41, 95% CI 1.16–7.10), higher PHQ-8 (OR = 1.260, 95% CI 1.16–1.37), and GAD-7 scores (OR = 1.19, 95% CI 1.10–1.30) increased the risk to suffer from clinical burnout. COVID-19-related variables were mostly not related/associated to burnout levels. Conclusion: In Italy, physicians’ burnout is moderately prevalent also in the chronic phase of the pandemic, with its determinants being more intrinsic than environmental. The development of effective interventions is needed to help physicians cope with the new challenges of their job.

Background: Fibromyalgia patients can benefit from music approaches as complementary treatments. In the literature, it was shown that these interventions managed pain conditions as well as reduced complaints, increased relaxation, and improved moods. Objective: This study aimed at evaluating music therapy, in the form of therapeutic music listening, specifically for patients with fibromyalgia, to treat chronic pain by reducing pain perception, increasing well-being, and improving quality of life. Methods: Twenty-four patients with fibromyalgia were recruited to take part in this feasibility pilot study that adopted a between-subject and within-subject design. Participants were randomised into three groups: (1) standard care, (2) standard care plus preferred music listening, (3) standard care plus Melomics-Health music listening, composed by an algorithm. Participants in experimental groups listened to 30 min of music at home, twice a day for a month. Patients’ perceptions of changes following the listening, the intensity of pain and its interference in their lives, physical and mental well-being, and reported attitudes towards listening to music were evaluated respectively through the patients’ global impression of change, the brief pain inventory, the Short Form Healthy Survey-12, and the cognitive behavioural assessment-outcome evaluation. Results: The study showed that music listening can significantly affect mental well-being compared to no music. Moreover, the effects in the Melomics-Health group are maintained at follow-up. No significant effect on pain perception was noted. Conclusions: The study provides information supporting a possible role of music listening in improving well-being of patients with fibromyalgia.

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.

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.

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.

Background: This study compares the performance at the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) across the healthy adult lifespan in an Italian population sample. Methods: The MMSE and MoCA were administered to 407 Italian healthy native-speakers (165 males; age range 20–93 years; education range 4–25 years). A generalized Negative Binomial mixed model was run to profile MMSE and MoCA scores across 8 different age classes (≤ 30; 31–40; 41–50; 51–60; 61–70; 71–80; 81–85; ≥ 86) net of education and sex. Results: MMSE and MoCA total scores declined with age (p < 0.001), with the MoCA proving to be “more difficult” than the MMSE (p < 0.001). The Age*Test interaction (p < 0.001) indicates that the MoCA proved to profile a sufficiently linear involutional trend in cognition with advancing age and to be able to detect poorer cognitive performances in individuals aged ≥ 71 years. By contrast, MMSE scores failed in capturing the expected age-related trajectory, reaching a plateau in the aforementioned age classes. Discussion: The MoCA seems to be more sensitive than the MMSE in detecting age-related physiological decline of cognitive functioning across the healthy adult lifespan. The MoCA might be therefore more useful than the MMSE as a test for general cognitive screening aims.

Background: Patients with post-infective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often show both short- and long-term cognitive deficits within the dysexecutive/inattentive spectrum. However, little is known about which cognitive alterations are commonly found in patients recovered from SARS-CoV-2, and which psychometric tools clinicians should consider when assessing cognition in this population. The present work reviewed published studies to provide a critical narrative of neuropsychological (NPs) deficits commonly observed after SARS-CoV-2 infection and the tests most suited for detecting such cognitive sequelae depending on illness severity. Methods: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was pre-registered on Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253079). Observational studies quantitatively assessing cognition in patients with post-infective SARS-CoV-2 were considered. From 711 retrieved articles, 19 studies conducted on patients with SARS-CoV-2 without medical comorbidities were included and stratified by disease severity. Results: The majority of studies (N = 13) adopted first-level tests. The most frequently administered screeners were the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE)—with the former more likely to detect mild, and the latter moderate/severe deficits. Among second-level tests, those assessing attention and executive functions (EFs) were highly represented. Remotely-delivered tests yielded lower percentages of cognitive impairment. Overall, cognitive domains often found to be impaired were EFs, attention, and memory. Conclusion: Cognitive sequelae in patients with post-infective SARS-CoV-2 can be detected with NPs testing. Depending on the psychometric test features, the likelihood of observing cognitive deficits can vary. Further studies on larger sample sizes are needed to investigat

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.

Background: Psychometric instruments assessing behavioural and functional outcomes (BFIs) in neurological, geriatric and psychiatric populations are relevant towards diagnostics, prognosis and intervention. However, BFIs often happen not to meet methodological-statistical standards, thus lowering their level of recommendation in clinical practice and research. This work thus aimed at (1) providing an up-to-date compendium on psychometrics, diagnostics and usability of available Italian BFIs and (2) delivering evidence-based information on their level of recommendation. Methods: This review was pre-registered (PROSPERO ID: CRD42021295430) and performed according to PRISMA guidelines. Several psychometric, diagnostic and usability measures were addressed as outcomes. Quality assessment was performed via an ad hoc checklist, the Behavioural and Functional Instrument Quality Assessment. Results: Out of an initial N = 830 reports, 108 studies were included (N = 102 BFIs). Target constructs included behavioural/psychiatric symptoms, quality of life and physical functioning. BFIs were either self- or caregiver-/clinician-report. Studies in clinical conditions (including neurological, psychiatric and geriatric ones) were the most represented. Validity was investigated for 85 and reliability for 80 BFIs, respectively. Criterion and factorial validity testing were infrequent, whereas content and ecological validity and parallel forms were almost never addressed. Item response theory analyses were seldom carried out. Diagnostics and norms lacked for about one-third of BFIs. Information on administration time, ease of use and ceiling/floor effects were often unreported. Discussion: Several available BFIs for the Italian population do not meet adequate statistical-methodological standards, this prompting a greater care from researchers involved in their development.

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.

Background: In Parkinson's disease (PD), verb-naming tasks (VNTs) have been proposed as superior to noun-naming ones in detecting language deficits, although such a hypothesis is not supported at a statistical level. Objectives: The main aim of this study was to provide diagnostic accuracy evidence for a VNT and noun-naming task (NNT) in detecting cognitive impairment (CI) in PD patients. Method: Thirty-three consecutive PD patients were subdivided into participants with (PD-CI; N = 12) or without CI (cognitively unimpaired, PD-CU; N = 21), based on a raw score ≤25 or >25 on the Mini-Mental State Examination, respectively. The NNT and VNT by Neuropsychologia [2006 Jan;44(1):73-89] were administered. Diagnostic accuracy of the NNT and VNT was assessed through receiver-operating characteristics analyses by comparing PD-CU to PD-CI patients. At the optimal cut-off, sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios (LR+, LR-) were separately tested for the NNT and VNT against PD-CU versus PD-CI classification. Results: Diagnostic accuracy was higher for the NNT (AUC = 0.85; p = 0.001) versus the VNT (AUC = 0.68; p = 0.092). Consistently, the NNT yielded higher sensitivity, specificity, and post-test features than the VNT (NNT: sensitivity = 0.75, specificity = 0.81, PPV = 0.69, NPV = 0.85, LR+ = 3.94, LR- = 0.31; VNT: sensitivity = 0.67, specificity = 0.67, PPV = 0.53, NPV = 0.78, LR+ = 2, LR- = 0.5). Conclusions: In accordance with the Movement Disorders Society guidelines, NNTs are diagnostically sound psychometric instruments to discriminate PD patients with versus without CI. However, these findings need replication by (1) employing a gold standard different from the Mini-Mental State Examination, which does not capture the full range of CI in this population and (2) subdividing PD patients into those with mild CI and dementia.

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.]

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.

Background: Cognitive dysfunctions, both subjective and detectable at psychometric testing, may follow SARS-CoV-2 infection. However, the ecological-functional relevance of such objective deficits is currently under-investigated. This study thus aimed at investigating the association between objective cognitive measures and both physical and cognitive, ecological-functional outcomes in post-COVID-19. Methods: Forty-two COVID-19-recovered individuals were administered the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The Functional Independence Measure (FIM) was adopted to assess functional-ecological, motor/physical (FIM-Motor) and cognitive (FIM-Cognitive) outcomes at admission (T0) and discharge (T1). Results: When predicting both T0/T1 FIM-total and-Motor scores based on MMSE/MoCA scores, premorbid risk for cognitive decline (RCD) and disease-related features, no model yielded a significant fit. However, the MoCA - but not the MMSE significantly predicted T0/T1 FIM-Cognitive scores. The MoCA was significantly related only to T0/T1 FIM-Cognitive Memory items. Discussion: Cognitive measures are not associated with physical/motor everyday-life outcomes in post-COVID-19 patients. The MoCA may provide an ecological estimate of cognitive functioning in this population.