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In two studies, we used the Gottschaldt’s Hidden Figure Test (GHFT) for assessing figure disembedding ability in children aged 7–11. Study 1 demonstrated in a large sample of typically developing children that GHFT accuracy and time scores differed across age groups, without sex and socioeconomic differences. Thus, we provided normative data only taking into account children’s age. In Study 2, GHFT normative values were used to assess children with autism, who were also compared with a closely age-matched group of typical controls. Children with autism achieved time scores at or above the 50th centile and significantly differed from the controls for time score. The GHFT seems a valuable tool for defining the cognitive profile of children with autism.

Congestive heart failure (CHF) has been proposed as a possible cause of cognitive dysfunction but only a few studies have directly assessed cognitive performance in CHF. The aim of the present study was to compare the cognitive patterns of patients with CHF and patients having cardiovascular diseases uncomplicated by CHF (no-CHF group). In a multicenter observational case-control study, we studied 149 hospitalized elderly CHF patients in the New York Heart Association (NYHA) class II (CHFm, m: moderate), 159 CHF patients in NYHA class III-IV (CHFs, s: severe), and 207 no-CHF patients. Patients underwent a multidimensional assessment and neuropsychological tests for the following cognitive domains: attention, visual-spatial intelligence, verbal attainment, verbal and visuo-spatial memory. Neuropsychological performances of groups were compared by multivariate analysis. Correlates of an abnormal performance on at least three neuropsychological tests were assessed by logistic regression analysis. CHFs performed worse than no-CHF patients on 4 of the 7 neuropsychological measures, the largest difference being in tests of attention and verbal learning (p < 0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001). The following qualified as independent correlates of the outcome at logistic regression analysis: CHFs group membership (Odds Ratio-OR = 2.56, 95% Confidence Interval-CI = 1.49-4.40), depression (OR = 2.37, 95% CI = 1.54-3.66), hypertension (OR = 1.88, 95% CI = 1.18-2.99). Our results demonstrate that cognitive impairment is common among CHF patients and seems to be causally related to CHF severity, depression and hypertension. The cognitive dysfunction also characterizes a relevant fraction of patients with cardiovascular diseases uncomplicated by CHF.

Introduction: Common assessment tools for aphasia evaluate single language impairments but not their functional impact on patient’s communication skills in daily life. The lack of tools focused on ecological aspects might affect the choice of rehabilitative trainings. The Communicative Effectiveness Index (CETI) represents an attempt to assess the communicative abilities in “ecologic” context. This study aimed to explore psychometrics properties of the Italian translation and adaptation of CETI (I-CETI). Methods: Sixty-eight patients with aphasia due to left hemispheric stroke admitted to post-acute rehabilitation units and their relatives were included in the study. Data were collected in three different sessions. At study entry, patients were assessed for language, depression, and functional abilities, while their caregivers and speech therapists independently completed the I-CETI to assess inter-rater agreement (baseline). One week later, caregivers and speech therapists completed again I-CETI, to assess test-retest reliability (T1). Last, at discharge, patients completed again the evaluation protocol, and caregivers and speech therapists completed I-CETI (T2). Results: I-CETI showed high internal validity, excellent reliability, and good correlation between scores obtained by speech therapists and caregivers. Moreover, scores of I-CETI had quite good correlations with a traditional tool to assess language, and with measures of functional independence both at study entry and at discharge. Discussion: I-CETI showed good psychometric proprieties. These results allowed considering I-CETI as a reliable tool to assess effects of speech treatments on the communicative abilities in patients with aphasia. Furthermore, I-CETI might help clinicians to develop treatments more tailored on the “ecologic” difficulties of patients.

ObjectiveThe quarantine/self-isolation measures implemented to retard the spread of the 2019 coronavirus disease (COVID-19) may negatively affect the mental health of the population. The present study aimed to explore the impact of the psychological symptoms on the occurrence of cognitive failures in a large sample of home-dwelling Italian individuals during quarantine/self-isolation for COVID-19.MethodsWe employed an online questionnaire using a virtual platform of Google Moduli. The questionnaire included an assessment of cognitive failures evaluated by the Perceived Memory and Attentional Failures Questionnaire (PerMAFaQ) and of resilience, coping style, depression, anger, and anxiety.ResultsThe online questionnaire was completed by 4175 participants revealing that about 30% of participants complained of cognitive failures at least sometimes during quarantine/self-isolation, whereas some respondents reported very frequent cognitive failures. Moreover, resilience was found to mediate the relationships between depressive and anger symptoms and cognitive failures. Although no difference was found on PerMAFaQ among smart-workers, non-smart-workers, and those currently not at work, people not working at the moment complained of more frequent cognitive failures.ConclusionsThese findings indicate the need to implement psychological support intervention, particularly for vulnerable groups, to reduce anxiety, depression, and anger, and of psychoeducational interventions to enhance resilience reducing possible long-term cognitive consequences of the quarantine.

A relationship between sleep disorders and cognitive dysfunctions was reported in Parkinson’s Disease (PD), however, some studies did not confirm the link. A meta-analytic study was performed to investigate the relationship between sleep disorders and cognitive dysfunctions, and to clarify the evolution of cognitive status in PD patients with sleep disorders. The systematic literature search was performed up to November 2020 using PubMed, Scopus, and PsycINFO databases. We included studies published in peer-reviewed journals in English providing results about neuropsychological comparison between patients with or without sleep disorders. Meta-analysis on cross-sectional data included 54 studies for REM Sleep Behavior Disorder (RBD), 22 for Excessive Daytime Sleepiness (EDS), 7 for Obstructive Sleep Apnea (OSA), 13 for Restless Legs Syndrome (RLS), and 5 for insomnia, the meta-analysis on longitudinal data included 7 studies. RBD was related to deficits of global cognitive functioning, memory, executive functions, attention/working memory, language, and visuospatial abilities. EDS was associated with deficits of global cognitive functioning and attention and working memory abilities, whereas RLS and OSA were related to global cognitive dysfunction. Moreover, we revealed that PD patients with RBD and those with EDS performed worse than PD patients without sleep disorders at follow-up rather than baseline evaluation. Our results suggest that sleep disorders are associated with cognitive deficits supporting indirectly that these, especially the REM Sleep Behavior Disorder, reflect abnormalities of frontal networks and posterior cortical areas. Sleep disorders in patients with PD seem to also increase the risk for long-term cognitive decline.

Subjective memory complaint is a self-reported memory impairment which affects elderly people. This problem does not interfere with daily living activities but could decrease quality of life. This study's purpose was to verify whether a specific, newly developed, autobiographical recall training could modify self-perception of memory of subjects with subjective memory complaint. Seven elderly subjects (4 women and 3 men; mean age 65.5 yr., SD = 11) with such complaint, evidenced through a specific questionnaire, attended the training course and were prospectively assessed on standard neuropsychological tests, depressive symptomatology, and self-perception of memory. Self-perception of memory, as assessed by scores on a formalized questionnaire, improved significantly after the training, while depressive symptoms did not change. Neuropsychological performances were normal before and after the training, but a statistically significant improvement was observed only on the phonological fluency test. Thus the present pilot study suggested that the training may be effective in improving self-perception of memory and metamnestic capacity in elderly people with subjective memory complaints but not in changing subjects' depressive symptoms. This requires replication of this work with a much larger sample so statistical power is adequate.

Background and purpose. Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Since an accurate prognosis is essential for decision-making on patients’ management, we analysed data from an international multicentre prospective cohort study to evaluate two-year mortality rate and bedside predictors of mortality. Methods. We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and non-traumatic brain injury within 3 months post-injury. At enrolment we collected demographic (age; sex), anamnestic (etiology; time post-injury), clinical (Coma Recovery Scale Revised, CRS-R; Disability Rating Scale; Nociception Coma Scale-Revised) and neurophysiologic (EEG; somatosensory evoked and event-related potentials) data. Patients were followed-up to gather data on mortality up to 24 months post- injury. Results. Among 143 traumatic (n=55) and non-traumatic (n=88) patients (VS/UWS=68, 19 females; MCS=75, 22 females), 41 (28.7%) died within 24 months post-injury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p Conclusions. This study demonstrated that a feasible multimodal assessment in the post-acute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients’ families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

People can decide whether the image of a hand represents a left or a right one. The laterality judgment mainly implies mentally imaging own hand movement (motor simulation) if the stimulus represents a palm, or analysing visual cues, as hand asymmetry, if the stimulus reproduces a dorsum. Here, by capitalizing on evidence underscoring the key role of thumb-palm complex in motor dexterity of human hand, we hypothesise that activation of motor or visual processes when judging hand laterality is due to the different relevance of palm-thumb and dorsum-thumb combinations to hand action. To test this thumb-anchored strategy, in a laterality judgment experiment, we concurrently manipulated the thumb position (flexed or extended) with respect to palm and dorsum, and the human likeness of the hand shape (influencing the salience of the thumb with respect to the hand shape). The main results demonstrated that viewing the flexed thumb from palm or dorsum elicited motor simulation, while viewing the extended thumb activated motor simulation when combined with palm but not dorsum. The present data highlight the pivotal role of the thumb in hand laterality judgments, consistent with its key role in human in-hand manipulation.

Background Subjective complaints of cognitive deficits are not necessarily consistent with objective evidence of cognitive impairment in Parkinson’s disease (PD). Here we examined the factors associated with the objective-subjective cognitive discrepancy. Methods We consecutively enrolled 90 non-demented patients with PD who completed the Parkinson’s Disease Cognitive Functional Rating Scale (subjective cognitive measure) and the Montreal Cognitive Assessment (MoCA; objective cognitive measure). The patients were classified as “Overestimators”, “Accurate estimators”, and “Underestimators” on the basis of the discrepancy between the objective vs. subjective cognitive measures. To identify the factors distinguishing these groups from each other, we used chi-square tests or one-way analyses of variance, completed by logistic and linear regression analyses. Results Forty-nine patients (54.45%) were classified as “Accurate estimators”, 29 (32.22%) as “Underestimators”, and 12 (13.33%) as “Overestimators”. Relative to the other groups, the “Underestimators” scored higher on the Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and Parkinson Anxiety Scale (p p p p Conclusion In more than 45% of consecutive non-demented patients with PD, we found a ‘mismatch’ between objective and subjective measures of cognitive functioning. Such discrepancy, which was related to the presence of fatigue and depressive symptoms and frontal executive impairments, should be carefully evaluated in clinical setting.

Objective: For the first time, we administered reversing prism exposure to treat optic ataxia in a single patient with Balint-Holmes Syndrome (BHS), who also underwent specific trainings for simultanagnosia and ocular apraxia. Method and Results: By an introduction and withdrawal experimental design, we observed that the active treatment periods improved patient’s visuospatial defects and functional autonomy. Conclusions: We thus provided a proof of principle supporting the use of reversing prism exposure in optic ataxia within an integrated and personalized rehabilitative approach for BHS.

Background: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson’s disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM. Methods: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances. Results: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD. Conclusion: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.

Drawing is a multi-component process requiring a wide range of cognitive abilities. Several studies on patients with focal brain lesions and functional neuroimaging studies on healthy individuals demonstrated that drawing is associated with a wide brain network. However, the neural structures specifically related to drawing remain to be better comprehended. We conducted a systematic review complemented by a meta-analytic approach to identify the core neural underpinnings related to drawing in healthy individuals. In analysing the selected studies, we took into account the type of the control task employed (i.e. motor or non-motor) and the type of drawn stimulus (i.e. geometric, figurative, or nonsense). The results showed that a fronto-parietal network, particularly on the left side of the brain, was involved in drawing when compared with other motor activities. Drawing figurative images additionally activated the inferior frontal gyrus and the inferior temporal cortex, brain areas involved in selection of semantic features of objects and in visual semantic processing. Moreover, copying more than drawing from memory was associated with the activation of extrastriate cortex (BA 18, 19). The activation likelihood estimation coordinate-based meta-analysis revealed a core neural network specifically associated with drawing which included the premotor area (BA 6) and the inferior parietal lobe (BA 40) bilaterally, and the left precuneus (BA 7).These results showed that a fronto-parietal network is specifically involved in drawing and suggested that a crucial role is played by the (left) inferior parietal lobe, consistent with classical literature on constructional apraxia.

Previous imaging studies suggested that impairments of prefrontal-striatal and limbic circuits are correlated to excessive gambling. However, the neural underpinnings of gambling disorder (GD) continue to be the topic of debate. The present study aimed to identify structural changes in GD and differentiate the specific brain activity patterns associated with decision-making and reward-processing. We performed a systematic review complemented by Activation likelihood estimation (ALE) meta-analyses on morphometric and functional studies on neural correlates of GD. The ALE meta-analysis on structural studies revealed that patients with GD showed significant cortical grey-matter thinning in the right ventrolateral and ventromedial prefrontal cortex compared to healthy subjects. The ALE meta-analyses on functional studies revealed that patients with GD showed a significant hyperactivation in the medial prefrontal cortex and in the right ventral striatum during decision-making and gain processing compared to healthy subjects. These findings suggest that GD is related to an alteration of brain mechanisms underlying top-down control and appraisal of gambling-related stimuli and provided indications to develop new interventions in clinical practice.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC). Design: multi-center cross-sectional observational study. Setting: 23 intensive neurorehabilitation units. Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular=125, traumatic=83, anoxic=56, others=14). Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity. Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO. Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Introduction: Psychological factors can underlie fatigue in neurological disorders, but its relationship to fatigue in Parkinson's disease (PD) has not been explored. We assessed the association between maladaptive metacognitive beliefs and presence of fatigue in PD. Methods: Ninety-eight consecutive outpatients with PD (61% male; median age: 66.50 years) were assessed in terms of demographic, clinical, medication treatment, cognitive, or behavioural characteristics including metacognitive beliefs (Metacognitions Questionnaire-30 or MCQ). Fatigue was ascertained by PD-related diagnostic criteria. Univariate statistical approach (Mann-Whitney and Pearson chi-square tests) was used to compare PD patients with (f-PD) or without (nf-PD) fatigue in terms of demographic, clinical, medication treatment, cognitive, behavioural, and metacognitive measures. Results: Twenty-one PD patients (21%) displayed fatigue. The f-PD group scored higher on the MCQ-total score, MCQ-Cognitive Confidence subscale, and all behavioral measures (ps < 0.01) relative to nf-PD. They also had a more advanced Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale-III score. Conclusion: Maladaptive metacognitive beliefs such as the lack of cognitive confidence may play a key role to trigger and maintain fatigue in PD. Future studies, using a multivariate statistical approach, are needed to confirm these preliminary findings in a larger sample of patients with fatigue and to assess if modification of such metacognitive beliefs has the potential to ameliorate fatigue in PD.

Multiple sclerosis (MS) is associated with a high prevalence of emotional and mood disorders. Emotional disorders may worsen during illness progression and affect the quality of life of patients and their families. MS is often associated with depression, with an increased risk of suicide, poor adherence to treatment, decreased functional status, and quality of life. The diagnosis and treatment of emotional and mood disorders in these patients is often challenging since several symptoms of these disorders overlap with those of MS. Other prevalent emotional disorders in MS include bipolar disorder, anxiety disorders, emotional blunting (apathy), and pseudobulbar affect. Early recognition and treatment of these comorbidities could contribute to the reduction of disability and even to decreased mortality. The aim of this chapter is to provide an up-to-date review of mood and emotional disorders that are often associated with MS, focusing on their epidemiology, clinical features, pathogenesis, assessment, and treatment. The interplay between the psychosocial impact of the chronic disability and the demyelinating structural lesions of the brain in precipitating emotional and mood disorders is discussed, as well as its implications for diagnosis and treatment.

During prism adaptation (PA), active exposure to an optical shift results in sustained modifications of the sensorimotor system, which have been shown to expand to the cognitive level and serve as a rehabilitation technique for spatial cognition disorders. Several models based on evidence from clinical and neuroimaging studies offered a description of the cognitive and the neural correlates of PA. However, recent findings using noninvasive neurostimulation call for a reexamination of the role of the primary motor cortex (M1) in PA. Specifically, recent studies demonstrated that M1 stimulation reactivates previously vanished sensorimotor changes 1 day after PA, induces after-effect strengthening, and boosts therapeutic effects up to the point of reversing treatment-resistant unilateral neglect. Here, we articulate findings from clinical, neuroimaging, and noninvasive brain stimulation studies to show that M1 contributes to acquiring and storing PA, by means of persisting latent changes after the behavioral training is terminated, consistent with studies on other sensorimotor adaptation procedures. Moreover, we describe the hierarchical organization as well as the timing of PA mechanisms and their anatomical correlates, and identify M1 as an anatomo-functional interface between low- and high-order PA-related mechanisms.

Fatigue is a common and disabling nonmotor manifestation in patients with Parkinson’s disease (PD), and the supplementary motor area (SMA) has been implicated in its pathophysiology. SMA is usually divided in its rostro-caudal axis, with the rostral (pre-) SMA playing a major role in motor planning, and the caudal (proper) SMA related to movement execution. To investigate brain functional connectivity of SMA subregions in de novo, drug-naïve PD patients affected by fatigue, 17patients with fatigue, 18 without fatigue, and 16 matched healthy controls were recruited. All the participants were not depressed and did not suffer from daytime sleepiness. Parkinson Fatigue Scale (PFS) was used for fatigue screening (cut-off > 3.3 points) and severity rating. Seed-based resting-state functional MRI was used to compare the functional connectivity from bilateral SMA subregions to the whole brain. Voxel-based morphometry analysis was employed to test whether functional connectivity results were related to brain structural differences. PD-related fatigue was associated with an increased connectivity between the left pre-SMA and the left postcentral gyrus as well as a decreased connectivity between the left SMA proper and the left middle frontal gyrus (ps < 0.01). These patterns of functional connectivity were tightly correlated with PFS scores (Pearson’s rs < 0.01). No structural brain changes were observed. In early PD, altered functional connectivity of both SMA subregions might play a crucial role in fatigue pathophysiology. These results offer new insights into the mechanisms responsible for fatigue in PD, suggesting possible targets for neuromodulation strategies oriented to modulate the SMA activity.

Introduction: Previous studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet. Methods: One-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of sample's features on results was controlled by logistic regression and Quade's rank analysis. Results: Twenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (ps < 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue. Conclusion: Fatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.

Mild cognitive impairment associated with Parkinson's disease (PD) is a risk factor for the development of dementia. Despite the importance of early identification of mild cognitive impairment in PD, its prevalence and clinical correlates are still debated. The present meta-analysis provides a robust estimate of prevalence rate of mild cognitive impairment in PD according to the Movement Disorder Society clinical criteria and to explore the differences between PD patients with and without mild cognitive impairment in demographic, clinical, and neuropsychiatric features. A systematic literature search was performed up to April 2019 using PsycInfo (PROQUEST), PubMed, and Scopus. From 4706 titles and abstracts, 41 studies were selected (n = 7053 patients). Pooled mild cognitive impairment prevalence was 40% on a total sample of 7053 PD patients (95% confidence interval = 36–44; Q = 490.14, P < 0.0001; I2 = 91.84%) with a higher frequency for the multiple domain subtype (31%; 95% confidence interval = 23–41, Q = 93.24; P < 0.0001; I2 = 92.49%). Meta-regression analysis revealed that stage of PD moderate prevalence estimates of mild cognitive impairment (β = 2.80; P = 0.008). Mild cognitive impairment in PD was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose, more severe motor symptoms, and postural instability/gait difficulty motor subtype, poorer quality of life, higher levels of apathy, and depression. The present meta-analysis indicated that mild cognitive impairment in PD is a frequent cognitive status deserving to be early detected by means of standardized cognitive assessments in clinical practice. © 2019 International Parkinson and Movement Disorder Society.

Introduction: Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time. Methods: Fifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up. Results: Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up. Conclusion: In early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.

Prism Adaptation (PA) is a behavioral task to assess visuo-motor plasticity and to ameliorate the symptoms of unilateral spatial neglect. Several studies have addressed the effects of PA on both sensory-motor and cognitive processing and the contribution of different brain regions to PA, although via non standardized procedures. The aim of the present review is to gather findings from the neuro-imaging and neuro-stimulation fields and put forward an interpretative framework for PA. The available evidence supports that sensory-motor effects of PA would mainly relate to the activation of a cerebello-parietal network, while the effects on spatial cognition would be mediated by bottom-up activation of temporal and prefrontal regions. The consolidation of PA effects would rely on activity of the motor cortex. The use of standardized PA procedures is strongly recommended for a systematic and accurate investigation of the neural mechanisms of PA.

Objective Patients with Huntington’s disease (HD) may show impairments of frontal cortical–subcortical circuits with difficulties on cognitive flexibility tasks. One marker of poor flexibility is “perseveration” behavior, which refers to inappropriate and involuntary production of iterative responses not adequate to the current task demands. This study explored frequency, type, and possible cognitive mechanisms of verbal perseverations in a large sample of HD patients. Method A sample of 128 patients with HD underwent phonological and category verbal fluency tests to assess perseverative errors, within a wide neuropsychological, psychopathological, motor, and functional assessment. Results Perseverative errors in verbal fluency task occurred in 89 (69.5%) patients. Patients showing perseverations scored significantly lower than patients without perseverations on tasks tapping executive and motor functions and on functional independence scales. Logistic regression analysis revealed a significant independent association of verbal perseverations with scores on Trail Making Test only. Conclusions: Verbal perseverations are frequent in HD patients and are likely related with impairments of attentional switching and working memory, hampering tracking of verbal responses already produced. Perseverative behavior may serve as a useful clinical marker of cognitive and functional impairment in patients with HD.

Background: The MIG-SCOG is a questionnaire to assess self-reported subjective cognitive symptoms during migraine attacks, consisting of 9 items evaluating executive functions and language. The aim of the study was to evaluate the psychometric properties of the Italian version of the MIG-SCOG (I-MIG-SCOG) in patients with migraine without aura. Methods: The I-MIG-SCOG underwent 20 Italian healthy subjects to assess its comprehensibility. Reliability and divergent validity of the I-MIG-SCOG were evaluated in a sample of 153 migraines without aura patients. They also underwent Montreal Cognitive Assessment, Beck Depression Inventory and Apathy Evaluation Scale. Results: The final I-MIG-SCOG was easily comprehensible. There were no missing data, no floor and ceiling effects; mean I-MIG-SCOG score was 7.54 ± 3.98; Cronbach’s alpha was 0.814. The I-MIG-SCOG score correlated poorly with Montreal Cognitive Assessment, Beck Depression Inventory and Apathy Evaluation Scale. Conclusion: The I-MIG-SCOG should represent a reliable and valid patient-centred and disease-related instrument to identify cognitive symptoms experienced during migraine attacks and to monitor the divergent effects of symptomatic treatments on cognitive functions also in Italian migraine patients.

Introduction: Impulse control disorders (ICDs) in Parkinson's disease (PD) are a group of impulsive behaviors most often associated, but not limited to, dopamine replacement therapy (DRT), particularly the use of dopamine agonists (DA). ICDs can impair activities of daily living and have a strong negative impact on quality of life of patients and their families. Areas covered: This review mainly focusses on the most common ICDs in the context of currently accepted management strategies for PD and emphasizes areas of controversy in need of further research. The authors further describe the concept of dopamine agonist withdrawal (DAWS) syndrome and its implication for the treatment of ICDs, the role of recently available antiparkinsonian drugs and routes of delivery, and non-pharmacological treatments. Expert opinion: When ICDs develop, proper management mainly consists of reducing, discontinuing or switching dopaminergic agents, especially of DA. In these scenarios, patients should be closely followed up as their motor condition may deteriorate along with occurrence of DAWS. Assessment of the presence and intensity of ICDs should be carried throughout the course of the disease and not only when a particular treatment is started or when the dosage is increased, since their occurrence is not linearly related to DRT alone.

Previous neuroimaging studies demonstrated that several brain areas are involved in detecting threats and activating defensive responses to threatening stimuli. The right premotor cortex (PM) is mainly activated during freezing, whereas the right temporoparietal junction (TPJ) is involved in attentional orienting towards threat. The aim of the present study was to test the possibility to modulate attentional orienting and defensive responses to threatening stimuli by interfering with the activity of the right TPJ and PM with cathodal. The results demonstrated that after sham stimulation the participants were slower to respond to threatening than to non-threatening stimuli, consistent with the idea that the experimental paradigm induced a freeze-like response to threatening stimuli. Active tDCS over PM reversed this response pattern, whereas TPJ stimulation wiped out the difference between responses to threatening and non-threatening stimuli. Our findings demonstrated that inhibitory stimulation of PM favours active defensive responses to threatening stimuli whereas TPJ inhibitory stimulation reduces attentional prioritizing of threatening stimuli. In conclusion, our study showed that it is possible to modulate responses to threatening stimuli by interfering with activity of at least two cortical regions of the brain network involved in dealing with threats.

Background Apathy is a predictor of cognitive decline in the course of multiple sclerosis (MS). Early identification of apathetic patients is relevant in clinical settings. Objective To assess applicability and psychometric properties of the self-rated version of the Dimensional Apathy Scale (DAS) in a large cohort of patients with MS and to compare its diagnosing accuracy with that of the Apathy Evaluation Scale (AES). Methods One hundred and twenty-four patients underwent clinical interview based on diagnostic criteria for apathy, DAS, AES, and assessment of depression, global cognitive functioning, and non-verbal intelligence. Results According to diagnostic criteria, apathy occurred in 33.4% of the patients. The DAS showed high consistency, and good convergent, discriminant and criterion validity. Factor analysis indicated a three-factor structure: executive, behavioural and emotional apathy. Unlike AES, no significant association between DAS score and severity of neurological disability (expressed by EDSS total score) was found, suggesting that the DAS might be less related to levels of disability. Receiver operating characteristics analyses, with clinical diagnostic criteria for apathy as the gold standard, revealed that a DAS score of 28/29 and an AES score of 35/36 were optimal cut-off values for identifying clinically relevant apathy. The two scales had similar diagnostic accuracy in the present sample. Conclusions The DAS is a valid and reliable multidimensional tool to assess apathy in MS, with diagnostic accuracy similar to that of the AES. However, the DAS score appears to be less strongly related to neurological disability.

Background Prospective memory (PM) deficits are often reported in multiple sclerosis (MS), but their relationship with neuropsychological characteristics and personality traits remains to be explored. Objective To systematically investigate both time-based and event-based PM abilities in a sample of MS without clinically relevant disability or global cognitive decline and to explore cognitive, neuropsychiatric characteristics and personality traits associated with PM deficits. Methods Thirty-three patients with MS and 33 healthy individuals were enrolled in the study. All participants underwent a standardized measure of PM to evaluate both time-based and event-based PM. Moreover, patients with MS completed the Brief Repeatable Battery to assess cognitive functioning, the Beck Depression Inventory-II and the Dimensional Apathy Scale to assess neuropsychiatric characteristics, and the NEO Personality Inventory-3 to assess personality traits. Results Individuals with MS demonstrated impaired time-based PM compared to healthy individuals. The regression analysis showed that poor performance in time-based PM was significantly related to lower extroversion and openness traits, whereas poor performance in event-based PM was significantly related to lower visuospatial memory abilities. Conclusions Low levels of openness and extroversion traits are associated with a greater risk of developing time-based PM deficit. Therefore, personality assessment and behavioural interventions should be encouraged in MS clinical practice.

Introduction The Fatigue Severity Scale (FSS-9) and the Parkinson Fatigue Scale (PFS-16) are commonly used for assessing fatigue in Parkinson's disease (PD). Here we validated the Italian version of these scales, assessed their psychometric properties by Rasch analysis, and computed their optimal cut-off scores using clinical diagnosis of PD-related fatigue as the gold standard. Methods PD patients (n = 167) completed the Italian versions of FSS-9 and PFS-16. Each item of PFS-16 was scored both on a 5-point (PFS-16polytomous) and on a 2-point scale (PFS-16dichotomous). Results All scales showed an adequate overall Rasch model fit, high reliability, and good discriminant, convergent, and concurrent validity, but were less accurate in measuring very high and very low fatigue levels. No evidence of differential item functioning with respect to age, sex, and severity of parkinsonian symptoms was found. Some items of FSS-9 (item 1), PFS-16polytomous (items 1 and 13), and PFS-16dichotomous (items 1, 8, and 13) showed misfit, possibly due to their content concerning sleep and motivation disorders. When FSS-9 and PFS-16polytomous’ responses were rescored on a 3-point scale, the discriminability across response categories improved. The optimal cut-off score in detecting clinically-diagnosed fatigue (observed in 20% of the sample) was 3.09 for PFS-16polytomous, 8.00 for PFS-16dichotomous, and 4.67 for FSS-9. Conclusions The Italian version of PFS-16 and FSS-9 showed sound psychometric properties and can be confidently used to quantify fatigue symptoms in PD, although clinical diagnosis of fatigue should rely on validated criteria. The PFS-16polytomous exhibited advantages with respect to PFS-16dichotomous.

Background. In the context of a causal relationship between stress and migraine, coping strategies are aimed at managing stressful life events and reducing the distressing emotions connected to them. Methods. Sixty-one consecutive patients with migraine without aura (MwoA) and sixty-one healthy controls (HCs) completed three self-report questionnaires assessing a broad range of coping (cognitive and behavioural) strategies: the Coping Orientation to Problems Experienced (COPE), the Coping Inventory for Stressful Situation (CISS), and the Proactive Coping Inventory (PCI). Moreover, the Perceived Stress Scale (PSS), a scale measuring self-perception of stress, global cognitive functioning, depressive symptoms, apathy, state, and trait anxiety, was administered to all participants. Results. No significant difference was found on the scales and subscales of PCI and CISS as well as in the PSS between MwoA patients and HCs. However, the two groups showed different scores in the subscale “turning to religion” of COPE (22.08±5.19 in migraineurs vs. 24.70±4.44 in HCs, p=0.003). A significant negative correlation of the turning to religion score with the HIT-6 score was found. Conclusions. The present study revealed that MwoA patients show a significantly reduced use of the “turning to religion” approach, an emotion-focused coping strategy. Although migraine patients appeared to be less oriented to transcendent (that means a reduced utilization of an adaptive coping strategy), they did not perceive daily living as more stressful than HCs. Finally, the reduced utilization of the “turning to religion” coping strategy is associated with a great impact of migraine on ability to function on the job or at school, at home, and in social situations in migraine patients.

Background: Recent evidence has converged in showing that the lateral occipitotemporal cortex is over-recruited during implicit motor imagery in elderly and in patients with neurodegenerative disorders, such as Parkinson&rsquo, s disease. These data suggest that when automatically imaging movements, individuals exploit neural resources in the visual areas to compensate for the decline in activating motor representations. Thus, the occipitotemporal cortex could represent a cortical target of non-invasive brain stimulation combined with cognitive training to enhance motor imagery performance. Here, we aimed at shedding light on the role of the left and right lateral occipitotemporal cortex in implicit motor imagery. Methods: We applied online, high-frequency, repetitive transcranial magnetic stimulation (rTMS) over the left and right lateral occipitotemporal cortex while healthy right-handers judged the laterality of hand images. Results: With respect to the sham condition, left hemisphere stimulation specifically reduced accuracy in judging the laterality of right-hand images. Instead, the hallmark of motor simulation, i.e., the biomechanical effect, was never influenced by rTMS. Conclusions: The lateral occipitotemporal cortex seems to be involved in mental representation of the dominant hand, at least in right-handers, but not in reactivating sensorimotor information during simulation. These findings provide useful hints for developing combined brain stimulation and behavioural trainings to improve motor imagery.

Background: Few studies examined the effects of combined motor and cognitive rehabilitation in patients with multiple sclerosis (MS). The present prospective, multicenter, observational study aimed to determine the efficacy of an integrated cognitive and neuromotor rehabilitation program versus a traditional neuromotor training on walking, balance, cognition and emotional functioning in MS patients. Methods: Sixty three MS patients were selected and assigned either to the Integrated Treatment Group (ITG; n = 32), receiving neuropsychological treatment (performed by ERICA software and paper–pencil tasks) complemented by conventional neuromotor rehabilitation, or to the Motor Treatment Group (n = 31) receiving neuromotor rehabilitation only. The intervention included two 60-min sessions per week for 24 weeks. At baseline and at end of the training all patients underwent a wide-range neuropsychological, psychological/emotional, and motor assessment. Results: At baseline the two groups did not differ for demographic, neuropsychological, psychological/emotional, and motor features significantly. After rehabilitation, only ITG group significantly (p-corrected for False Discovery Rate) improved on test tapping spatial memory, attention and cognitive flexibility, as well as on scales assessing depression and motor performance (balance and gait). A regression analysis showed that neuropsychological and motor improvement was not related to improvements in fatigue and depression. Conclusion: The present study demonstrated positive effects in emotional, motor, and cognitive aspects in MS patients who received an integrated cognitive and neuromotor training. Overall, results are supportive of interventions combining motor and cognitive training for MS.

Several processes are devoted to error reduction in response to a visual displacement, such as the one induced by wedge prisms. Strategic calibration and spatial realignment contribute to the iteratively process that allows a progressive adjustment of motor commands to reduce the magnitude of errors. Isolating the specific contributions to motor behaviour coming from these distinct processes is not possible using traditional single-step Prism Adaptation (PA), where participants are directly exposed to full prismatic shift. Here, we selectively investigated the effect of realignment on motor behaviour by means of a PA paradigm (the multiple-step PA) that allows to elude the development of strategic calibration. We tested for a specific cerebellar contribution to realignment by means of transcranial Direct Current Stimulation (tDCS) in healthy subjects. Confirming and expanding previous imaging and stimulation results, our study causally demonstrates cerebellar involvement in spatial realignment. Additionally, our results point to a possible contribution of the cerebellum in automatic online control. The role of a cortico-cerebellar network accounting for this results and possible clinical applications are proposed and discussed.

Patients with Parkinson’s disease (PD) can experience several behavioral symptoms, such as apathy, agitation, hypersexuality, stereotypic movements, pathological gambling, abuse of antiparkinsonian drugs, and REM sleep behavioral disorders. Psychoses and hallucinations, depression and anxiety disorders, and difficulties in recognizing and experiencing emotions also impair behavior and can cause severe psychosocial problems in patients with PD. Symptoms can be present since early stages of the disease, sometimes even before the appearance of classical motor symptoms, likely in relation to dopamine depletion in basal ganglia and/or to dysfunctions of other neurotrasmitter systems, and others can develop later, in some cases in relation to dopaminergic treatment. In this paper, we review recent literature, with particular attention to the last 5 years, on the main behavioral and emotional disturbances described in PD patients as well as the hypothesized neurofunctional substrate of such impairments. Finally, we provide some suggestions on the most suitable instruments to check and assess PD-associated behavioral defects over time.

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, a growing body of evidence demonstrated that PD encompasses several non-motor disturbances as well, such as cognitive impairment. Cognitive defects can be present since early stages of the disease but tend to dominate the clinical picture as the disease progresses. Around 40% of patients with PD present with cognitive impairments in several cognitive domains including attention, working memory and executive functions, language, visuospatial skills, and episodic memory; in later stages of the disease, cognitive defects and associated behavioral disorders concur to determine clinically relevant PD-associated dementia. Part of these defects is ascribed to a dopamine-dependent dysfunction of fronto-striatal pathways, but there is a considerable heterogeneity in the cognitive impairments as well as a suggestion of the role of other neurotransmitter systems, such as the cholinergic one, mainly responsible for Parkinson-dementia syndrome. In this paper, we review recent literature with particular attention to the last 5 years on the main cognitive deficits described in PD patients as well as on the hypothesized neuro-functional substrate of such impairments. Finally, we provide some suggestions on how to test cognitive functions in PD appropriately.

Introduction Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients. Methods Eighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue. Results Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745). Conclusion In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.

Verbal reasoning is a complex, multicomponent function, which involves activation of functional processes and neural circuits distributed in both brain hemispheres. Thus, this ability is often impaired after brain injury. The aim of the present study is to describe the construction of a new verbal reasoning test (VRT) for patients with brain injury and to provide normative values in a sample of healthy Italian participants. Three hundred and eighty healthy Italian subjects (193 women and 187 men) of different ages (range 16–75 years) and educational level (primary school to postgraduate degree) underwent the VRT. VRT is composed of seven subtests, investigating seven different domains. Multiple linear regression analysis revealed a significant effect of age and education on the participants’ performance in terms of both VRT total score and all seven subtest scores. No gender effect was found. A correction grid for raw scores was built from the linear equation derived from the scores. Inferential cut-off scores were estimated using a non-parametric technique, and equivalent scores were computed. We also provided a grid for the correction of results by z scores.

Background A complex relationship exists between postural control and cognition in the elderly. Namely, neural mechanisms that are required for the regulation of posture have been variably associated with cognitive dysfunctions. Parkinson's disease (PD) is the second most common neurodegenerative disease among the elderly, and it has been associated with both cognitive and postural abnormalities such as Pisa syndrome (PS). Although its onset has been considered to be multifactorial, the pathophysiological mechanisms underpinning PS are still not fully explained. Until now, no study investigated the possible contribution of cognitive dysfunction to occurrence of PS in PD. Patients and methods Twenty PD patients with PS and 20 PD patients without PS were enrolled. All patients with PD underwent neuropsychological battery to assess behavioural disturbances, memory, attention, frontal/executive and visuospatial functions. Results The two groups did not differ on demographic features, age at PD onset and disease duration, whereas they significantly differed on UPDRS-Part III, and levodopa-equivalent daily dose (LEDD). MANCOVA with above-mentioned clinical variable as covariates revealed significant differences on tasks tapping verbal long-term memory, and attentional and visuoperceptual abilities between groups. The binary logistic regression revealed that higher LEDD and lower performance on visuospatial task (Benton Judgment of Lines Orientation test) significantly predicted occurrence of PS. Conclusion Our results revealed a significant association of PS with altered attention and visuoperceptual functions in PD, suggesting that the occurrence of PS may be associated with alteration of both frontal–striatal systems and posterior cortical areas.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder caused by a small expansion of a short polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). It presents with adult onset of progressive eyelid drooping, swallowing difficulties and proximal limb weakness, usually without involvement of central nervous system (CNS). However, cognitive decline with relevant behavioural and psychological symptoms has been recently described in homozygous patients. In this study, we performed for the first time an extensive neuropsychological and neuropsychiatric evaluation on 11 OPMD heterozygote patients. We found that they were less efficient than a matched control sample on several tests, particularly those tapping executive functions. Moreover, the presence of negative correlation between GCN expansion size and some neuropsychological scores raises the issue that CNS involvement might be linked to the genetic defect, being worse in patients with larger expansion. Our results might be consistent with the toxic gain-of-function theory in the pathogenesis of OPMD and hint at a possible direct role of PABPN1 in the CNS also in heterozygote patients.

Cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) complicated by chronic hypoxemia, but the effect of cognitive training in patients with COPD has not been studied. The aim of the present study was to verify whether cognitive training can preserve cognitive abilities of patients with hypoxemic COPD. Our series consisted of 105 COPD patients with at rest (n = 36) or effort (n = 69) hypoxemia and free from concurrent dementing diseases. Neuropsychologic assessment included a screening test, the Mini Mental State Examination (MMSE), and a standardized confirmatory battery of neuropsychological tests, the Mental Deterioration Battery (MDB). After baseline assessment, patients were randomized to receive standardized multidimensional care (standardization of pharmacological therapy, health education, selection of inhalers according to patient's ability, respiratory rehabilitation, nutritional counseling, oxygen therapy, and control visits) with (n = 53) or without (n = 52) cognitive training aimed at stimulating attention, learning, and logical-deductive thinking. Cognitive performance was reassessed after 1.5, 4, and 6 months. The analysis of variance for repeated measures (ANOVA) having the group membership (study vs. control) as grouping factor was used to assess changes in cognitive performance. Both intervention and control groups showed no significant changes in cognitive performance except for a trend toward improvement in verbal fluency and verbal memory, but cognitive intervention had no significant effect. In conclusion, cognitive training seems ineffective in COPD. However, a multidimensional standardized therapeutic approach, as it was indistinctly provided to all patients, could help to slow or prevent cognitive decline.

OBJECTIVE: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease responsible for an early onset cognitive impairment. Aim of our study was to test the cortical cholinergic innervation in CADASIL by short latency afferent inhibition (SAI) technique. METHODS: We applied SAI in ten CADASIL patients and in ten age-matched normal controls. SAI is a phenomenon observed on motor evoked potential when transcranial magnetic stimulation is delivered after a time ranging from 2 to 8 ms longer than the time needed by the peripheral nerve afferent input to reach the somatosensory cortex. RESULTS: The amount of short latency afferent inhibition was significantly smaller in CADASIL patients than in controls (79.5+/-21.7% Vs 42.7+/-14.1% of test size; p

The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also including subtests to assess frontal functions such as set-shifting, abstraction and cognitive flexibility. MoCA seems to be useful to identify non-amnestic mild cognitive impairment (MCI) and subcortical dementia; it has high sensitivity and specificity in distinguishing MCI from mild Alzheimer's Disease. Previous studies revealed that certain items of MoCA may be culturally biased and highlighted the need for population-based norms for the MoCA. The aim of present study was to collect normative values in a sample of Italian healthy subjects. Four hundred and fifteen Italian healthy subjects (252 women and 163 men) of different ages (age range 21-95 years) and educational level (from primary to university) underwent MoCA and Mini Mental State Examination (MMSE). Multiple linear regression analysis revealed that age and education significantly influenced performance on MoCA. No significant effect of gender was found. From the derived linear equation, a correction grid for MoCA raw scores was built. Inferential cut-off score, estimated using a non-parametric technique, is 15.5 and equivalent scores were computed. Correlation analysis showed a significant but weak correlation between MoCA adjusted scores with MMSE adjusted scores (r = 0.43, p < 0.001). The present study provided normative data for the MoCA in an Italian population useful for both clinical and research purposes.

Background and purpose Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naive untreated PD patients with or without clinically significant apathy. Methods Sixty-two PD patients with a disease duration

Cognitive impairment frequently occurs in elderly COPD patients, but little is known about its prognostic implications. We aimed at evaluating the prognostic role of cognitive impairment in patients with severe COPD.Our series consisted of 149 stable patients (mean [+/- SD] age, 68.7 +/- 8.5 years) with COPD and a Pao(2) of57 mm Hg at rest (n = 97) or at the end of the 6-min walking test (n = 37) who were enrolled in a prospective observational study. After a multidimensional baseline assessment, patients were followed up by telephone calls for a mean duration of 32.5 +/- 9.2 months (minimal follow-up duration, 24 months); 134 patients were successfully tracked. We used multivariable Cox proportional hazard analysis to identify predictors of death among clinical/functional variables that previously were shown to have prognostic implications and among neuropsychological indexes selected on the basis of univariate analysis.We observed 29 deaths over a median follow-up time of 32 months. Only the two following variables were independently associated with the outcome: an abnormal score on the copy with landmark test (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.34 to 6.39); and a 6-min walk distance of300 m (HR, 3.46; 95% CI, 1.15 to 10.5). A Pao(2) of57 mm Hg at rest (HR, 2.19; 95% CI, 0.93 to 5.18) and an FEV(1) of40% predicted (HR, 2.74; 95% CI, 0.99 to 7.57) were nearly significantly associated with the outcome, while Paco(2), body mass index, physical dependence, comorbid diseases, and the impairment of cognitive domains other than drawing impairment were unrelated to the outcome.Drawing impairment is a risk factor for mortality and might improve the assessment of hypoxemic COPD patients.

We tested 125 normal subjects and 24 right and 22 left focal brain-damaged patients (RBD and LBD) on the Rey figure copying test and on a battery of perceptual and representational visuospatial tasks, in search of relationships between constructional and visuospatial abilities. Selected RBD and LBD were not affected by severe aphasia, unilateral spatial neglect or general intellectual defects. Both RBD and LBD showed defective performances on the constructional task with respect to normal subjects. As regards visuospatial tasks, both patient groups scored lower than normal subjects in judging angle width and mentally assembling geometrical figures; moreover, RBD, but not LBD, achieved scores significantly lower than healthy controls in judging line orientation and analyzing geometrical figures. Post-hoc comparisons did not reveal any significant differences between RBD and LBD. Multiple regression analysis showed that visuospatial abilities correlate with accuracy in copying geometrical drawings in normal subjects and in RBD, but not in LBD. From a theoretical perspective, these findings support the idea that visual perceptual and representational abilities do play a role in constructional skills.

Apathy is a behavioural disturbance occurring alone or in concomitance with depression in Parkinson’s disease (PD). Here we present a validation study for the self-report version of the Apathy Evaluation Scale (AES-S), carried out in a sample of 60 non-demented, non-depressed untreated, drug-naïve, de novo PD patients; 20 patients of the sample (33.3 %) were classified as apathetic according to current clinical criteria. All enrolled patients completed the AES-S and a neurological and cognitive assessment. Mean AES-S score was 34.43. AES-S did not show floor or ceiling effect. Cronbach’s alpha was 0.872. Principal component analysis revealed three factors: the first (34.4 % of the variance) represented constitutive aspects of the construct of apathy; the second (8.5 % of the variance) represented a social dimension; the third factor (7.9 % of the variance) represented a dimension related to insight. With respect to clinical criteria for apathy considered as the gold standard, receiver operating characteristics curve analysis showed that a cut-off of 36/37 has the maximum discrimination power. High sensitivity and negative predictive values were obtained with cut-off scores of 33/34 or lower; high specificity and positive predictive values were obtained with cut-off scores of 38/39 or higher. AES-S score correlated with scores on frontal tasks, but not on Beck Depression Inventory, Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr scale. The AES-S is a reliable and valid questionnaire for detecting apathy in PD. For screening purposes a 33/34 cut-off score is indicated, but a 38/39 cut-off score is necessary when a high specificity is desired.

Background: The pharmacokinetics, efficacy, and safety of calcium channel blockers have rarely been investigated in the elderly. Gallopamil, a methoxy derivative of verapamil with calcium antagonistic properties, has been shown to be effective in the treatment of angina pectoris. Objective: The aim of this study was to assess the anti-ischemic action of gallopamil, its effects on left ventricular and autonomic function, and its pharmacodynamics and safety in elderly patients. Methods: We studied immediate-release (IR) and sustained-release (SR) formulations of gallopamil in 12 sedentary elderly patients with stable effort angina and angiographically documented coronary artery disease in a randomized, placebo-controlled, cross-over, double-blind trial. Following a run-in period, patients received either IR gallopamil 50 mg TID or SR gallopamil 100 mg BID for 28 days, after which patients crossed over to the alternate regimen. A washout period of 4 days was incorporated between the 2 treatment phases. Antianginal efficacy was assessed by monitoring the number of angina episodes per week and the amount of sublingual nitroglycerin consumed per week as well as sequential cycloergometer exercise testing 2 and 6 hours postdose. Patients underwent clinical examination, electrocardiography (ECG), echocardiography, 24-hour Holter ECG monitoring, and blood testing at the beginning of the study and at the end of each phase. On the last day of the active treatment period, sequential blood samples were collected to determine plasma levels of gallopamil. Results: Both IR and SR gallopamil reduced the number of angina episodes and the amount of nitroglycerin consumed per week. Gallopamil also reduced the number of ECG signs of ischemia at peak exercise testing, as well as symptomatic and asymptomatic ischemic episodes on 24-hour Holter ECG monitoring. IR and SR gallopamil did not affect left ventricular diameters, ejection fraction, and average heart rate, nor did they cause significant changes in heart rate variability. Peak plasma levels of gallopamil were reached rapidly after ingestion of the IR and SR formulations. The plasma concentrations of gallopamil and the norgallopamil metabolite were similar during the first 2 hours after administration of IR and SR gallopamil. Thereafter, patients who received the SR formulation showed significantly higher gallopamil (P < 0.05) and norgallopamil (P < 0.05) plasma concentrations than patients who received the IR formulation. The area under the concentration-time curve for SR gallopamil was significantly larger than for IR gallopamil; however, half-life, clearance, and peak plasma concentration were similar after IR and SR gallopamil treatment. Adverse effects, which were observed in 25% of patients, were minor and were not related to plasma levels of gallopamil; no patient suffered hemodynamic or major cardiac conduction abnormalities attributable to gallopamil. Conclusions: Our data suggest that both IR and SR gallopamil were effective in reducing signs and symptoms of ischemia in elderly patients with stable effort angina, with few adverse effects.