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.

The Arrows and Colors Cognitive Test (ACCT): A new verbal-motor free cognitive measure for executive functions in ALS.

BACKGROUND AND OBJECTIVE: The presence of executive deficits in patients with Amyotrophic Lateral Sclerosis is well established, even if standardized measures are difficult to obtain due to progressive physical disability of the patients. We present clinical data concerning a newly developed measure of cognitive flexibility, administered by means of Eye-Tracking (ET) technology in order to bypass verbal-motor limitations. METHODS: 21 ALS patients and 21 age-and education-matched healthy subjects participated in an ET-based cognitive assessment, including a newly developed test of cognitive flexibility (Arrows and Colors Cognitive Test-ACCT) and other oculomotor-driven measures of cognitive functions. A standard screening of frontal and working memory abilities and global cognitive efficiency was administered to all subjects, in addition to a psychological self-rated assessment. For ALS patients, a clinical examination was also performed. RESULTS: ACCT successfully discriminated between patients and healthy controls, mainly concerning execution times obtained at different subtests. A qualitative analysis performed on error distributions in patients highlighted a lower prevalence of perseverative errors, with respect to other type of errors. Correlations between ACCT and other ET-based frontal-executive measures were significant and involved different frontal sub-domains. Limited correlations were observed between ACCT and standard 'paper and pencil' cognitive tests. CONCLUSIONS: The newly developed ET-based measure of cognitive flexibility could be a useful tool to detect slight frontal impairments in non-demented ALS patients by bypassing verbal-motor limitations through the oculomotor-driven administration. The findings reported in the present study represent the first contribution towards the development of a full verbal-motor free executive test for ALS patients.

Cognitive-behavioral longitudinal assessment in ALS: the Italian Edinburgh Cognitive and Behavioral ALS screen (ECAS).

OBJECTIVE: The study presents data on the longitudinal administration of the Italian Edinburgh Cognitive and Behavioral ALS Screen (ECAS). We investigated cognitive-behavioral performance in a group of ALS patients over time and the feasibility of repeating the ECAS longitudinally compared with standard neuropsychological tests. Finally, correlations between clinical/genetic and cognitive/behavioral data were considered. METHODS: One hundred and sixty-eight ALS patients were tested at baseline (T0). Among these, 48 patients performed the ECAS after 6 months (T1), 18 patients performed it at T2 (12 months), and five patients were assessed after 24 months (T3). Participants were also administered two cognitive test (FAB; MoCA) and psychological questionnaires (BDI; STAI/Y). The FBI was carried out with caregivers. RESULTS: No cognitive deterioration was found across follow-ups. In contrast, although scores did not change between T0 and T1, scores improved significantly for ECAS Total/ALS Non-specific and Memory domains when the ECAS was repeated on three occasions (T0, T1, T2). Apathy/Inertia was the most common behavioral symptom, but no worsening of behavioral scores was detected over time. After 12-24 months, patients were still able to perform the ECAS in total, in contrast to FAB and MoCA, which were only partially administrable. CONCLUSIONS: The significant improvement of some ECAS scores over time supports the presence of possible practice effects, particularly in the memory domain, highlighting the need to accommodate for these in longitudinal assessments, through healthy controls groups or alternate versions. This work represents the first Italian ECAS follow-up study and confirms ECAS feasibility in patients with increasing physical disability.

The Complex Interplay Between Depression/Anxiety and Executive Functioning: Insights From the ECAS in a Large ALS Population.

Introduction: The observed association between depressive symptoms and cognitive performances has not been previously clarified in patients with amyotrophic lateral sclerosis (pALS). In fact, the use of cognitive measures often not accommodating for motor disability has led to heterogeneous and not conclusive findings about this issue. The aim of the present study was to evaluate the relationship between cognitive and depressive/anxiety symptoms by means of the recently developed Edinburgh Cognitive and Behavioral ALS Screen (ECAS), a brief assessment specifically designed for pALS. Methods: Sample included 168 pALS (114 males, 54 females); they were administered two standard cognitive screening tools (FAB; MoCA) and the ECAS, assessing different cognitive domains, including ALS-specific (executive functions, verbal fluency, and language tests) and ALS non-specific subtests (memory and visuospatial tests). Two psychological questionnaires for depression and anxiety (BDI; STAI/Y) were also administered to patients. Pearson's correlation coefficient was used to assess the degree of association between cognitive and psychological measures. Results: Depression assessment negatively correlated with the ECAS, more significantly with regard to the executive functions subdomain. In particular, Sentence Completion and Social Cognition subscores were negatively associated with depression levels measured by BDI total score and Somatic-Performance symptoms subscore. Conversely, no significant correlations were observed between depression level and cognitive functions as measured by traditional screening tools for frontal abilities (FAB) and global cognition (MoCA) assessment. Finally, no significant correlations were observed between state/trait anxiety and the ECAS. Discussion and conclusion: This represents the first study focusing on the relationship between cognitive and psychological components in pALS by means of the ECAS, the current gold standard for ALS cognitive-behavioral assessment. If confirmed by further investigations, the observed association between depression and executive functions suggests the need for a careful screening and treatment of depression, to avoid overestimation of cognitive involvement and possibly improve cognitive performances in ALS.

An eye-tracker controlled cognitive battery: overcoming verbal-motor limitations in ALS.

We assessed language, attention, executive, and social cognition abilities in a sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a recently developed cognitive battery based on oculomotor control with eye-tracking (ET) technology. Twenty-one ALS patients and 21 age- and education-matched healthy subjects underwent the ET-based cognitive assessment, together with the standard cognitive screening tools [Frontal Assessment Battery (FAB); Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]. Psychological measures of anxiety (State-Trait Anxiety Inventory-Y) and depression (Beck Depression Inventory) were also collected, and an ET usability questionnaire was administered. For patients, clinical and respiratory examinations were also performed, together with behavioural assessment (Frontal Behavioural Inventory). The developed battery discriminated among patients and controls with regard to measures of verbal fluency, frontal abilities, and social cognition. Measures of diagnostic utility confirmed a higher diagnostic accuracy of such ET-based tests with respect to FAB; similar diagnostic accuracy emerged when comparing them to the other standard cognitive tools (MoCA, WM). Usability ratings about the ET tests were comparable among the two groups. The ET-based neuropsychological battery demonstrated good levels of diagnostic accuracy and usability in a clinical population of non-demented ALS patients, compared to matched healthy controls. Future studies will be aimed at further investigate validity and usability components by recruiting larger sample of patients, both in moderate-to-severe stages of the disease and affected by more severe cognitive impairment.

Cognitive-constructivist Approach in Medical Settings: The Use of Personal Meaning Questionnaire for Neurological Patients' Personality Investigation.

Objective: The cognitive-constructivist psychotherapy approach considers the self as a continuous regulation process between present and past experience, in which attributions of meaning is characterized by the use of internal rules. In this conception, everyone would be driven by a specific inner coherence called Personal Meaning Organization (PMO). Such approach has never been applied to neurological patients by means of ad hoc developed tools. We performed an explorative study aimed to characterize personality styles in different neurological conditions within the theoretical framework of cognitive-constructivist model. Materials and Methods: Three groups of neurological patients (Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Primary Headache) and a sample of healthy participants, each composed by 15 participants, for a total of 60 participants, were recruited. The Personal Meaning Questionnaire (PMQ), an Italian questionnaire assessing PMOs construct, and other clinical tools for psychological and quality of life assessment were administered to all subjects. Results: The main finding concerned the detection, across all clinical conditions, of a higher prevalence of phobic personality style, with Amyotrophic Lateral Sclerosis showing a relevant prevalence of such PMO with respect to all other neurological conditions and controls. However, with respect to controls, in all clinical conditions, PMQ highlighted a tendency, even if not statistically significant, to codify experience by means of specific cognitive and emotional patterns. Conclusion: Our findings represent the first contribution towards understanding the personality profiles of patients affected by neurological conditions according to cognitive-constructivist theory.

An eye-tracking controlled neuropsychological battery for cognitive assessment in neurological diseases.

Traditional cognitive assessment in neurological conditions involving physical disability is often prevented by the presence of verbal-motor impairment; to date, an extensive motor-verbal-free neuropsychological battery is not available for such purposes. We adapted a set of neuropsychological tests, assessing language, attentional abilities, executive functions and social cognition, for eye-tracking (ET) control, and explored its feasibility in a sample of healthy participants. Thirty healthy subjects performed a neuropsychological assessment, using an ET-based neuropsychological battery, together with standard "paper and pencil" cognitive measures for frontal (Frontal Assessment Battery-FAB) and working memory abilities (Digit Sequencing Task) and for global cognitive efficiency (Montreal Cognitive Assessment-MoCA). Psychological measures of anxiety (State-Trait Anxiety Inventory-Y-STAI-Y) and depression (Beck Depression Inventory-BDI) were also collected, and a usability questionnaire was administered. Significant correlations were observed between the "paper and pencil" screening of working memory abilities and the ET-based neuropsychological measures. The ET-based battery also correlated with the MoCA, while poor correlations were observed with the FAB. Usability aspects were found to be influenced by both working memory abilities and psychological components. The ET-based neuropsychological battery developed could provide an extensive assessment of cognitive functions, allowing participants to perform tasks independently from the integrity of motor or verbal channels. Further studies will be aimed at investigating validity and usability components in neurological populations with motor-verbal impairments.

Cognitive assessment in Amyotrophic Lateral Sclerosis by means of P300-Brain Computer Interface: a preliminary study.

OBJECTIVE: To investigate the use of P300-based Brain Computer Interface (BCI) technology for the administration of motor-verbal free cognitive tests in Amyotrophic Lateral Sclerosis (ALS). METHODS: We recruited 15 ALS patients and 15 age- and education-matched healthy subjects. All participants underwent a BCI-based neuropsychological assessment, together with two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI-Y) and a usability questionnaire. For patients, clinical and respiratory examinations were also performed, together with a behavioural assessment (FBI). RESULTS: Correlations were observed between standard cognitive and BCI-based neuropsychological assessment, mainly concerning execution times in the ALS group. Moreover, patients provided positive rates concerning the BCI perceived usability and subjective experience. Finally, execution times at the BCI-based neuropsychological assessment were useful to discriminate patients from controls, with patients achieving lower processing speed than controls regarding executive functions. CONCLUSIONS: The developed motor-verbal free neuropsychological battery represents an innovative approach, that could provide relevant information for clinical practice and ethical issues. Its use for cognitive evaluation throughout the course of ALS, currently not available by means of standard assessment, must be addressed in further longitudinal validation studies. Further work will be aimed at refining the developed system and enlarging the cognitive spectrum investigated.

The validation of the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

This study presents the Italian validation of the recently developed Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a short screen for cognitive/behavioural alterations in patients with amyotrophic lateral sclerosis (ALS). We evaluated the psychometric properties of the ECAS Italian version in terms of reliability and convergent validity for both cognitive and behavioural features. Furthermore, we investigated the relationship with affective and clinical variables, in addition to ECAS usability and patients' insight into cognitive/behaviour changes. Finally, correlations between genetic and cognitive/behavioural data were analysed. We recruited 107 patients with ALS. Normative data were collected on 248 healthy subjects. Participants were administered the ECAS and two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI/Y) and an ad hoc usability questionnaire. The FBI was also carried out with caregivers. Results showed that the ECAS Italian version discriminated well between patients and controls. The most prevalent deficit occurred in executive functions and fluency. Correlations were observed between the ECAS and standard cognitive screening tools and between the ECAS carer interview and the FBI, supporting its full convergent validity. In conclusion, the ECAS Italian version provides clinicians with a rapid, feasible and sensitive tool, useful to identify different profiles of cognitive-behavioural impairment in ALS.

Antiglutamate Receptor Antibodies and Cognitive Impairment in Primary Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome have an increased risk to develop cognitive impairment. A possible role for antiphospholipid antibodies (aPL) and antiglutamate receptor (anti-NMDA) antibodies in the pathogenesis of neurological manifestations of these two conditions, have been suggested. In particular, the role of anti-NMDA antibodies in the pathogenesis of neuropsychiatric SLE is supported by several experimental studies in animal models and by the finding of a correlation between anti-NMDA positivity in cerebrospinal fluid and neurological manifestations of SLE. However, data from the literature are controversial, as several studies have reported a correlation of these antibodies with mild cognitive impairment in SLE, but more recent studies have not confirmed this finding. The synergism between anti-NMDA and other concomitant autoantibodies, such as aPL, can be hypothesized to play a role in inducing the tissue damage and eventually the functional abnormalities. In line with this hypothesis, we have found a high incidence of at least one impaired cognitive domain in a small cohort of patients with primary APS (PAPS) and SLE. Interestingly, aPL were associated with low scoring for language ability and attention while anti-NMDA titers and mini-mental state examination scoring were inversely correlated. However, when patients were stratified according to the presence/absence of aPL, the correlation was confirmed in aPL positive patients only. Should those findings be confirmed, the etiology of the prevalent defects found in PAPS patients as well as the synergism between aPL and anti-NMDA antibodies would need to be explored.

Counterfactual Thinking Deficit in Huntington's Disease.

BACKGROUND AND OBJECTIVE: Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving - all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington's Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment. METHODS: Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects. RESULTS: Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test - Part A, Phonemic Verbal Fluency Test and FAB. CONCLUSIONS: Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients' daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients' ability to analyse current behaviors and future actions.