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Introduction: Disturbances of balance control are common after stroke, affecting the quality of gait and increasing the risk of falls. Because balance and gait disorders may persist also in the chronic stage, reducing individual independence and participation, they represent primary goals of neurorehabilitation programs. For this purpose, in recent years, numerous technological devices have been developed, among which one of the most widespread is the Lokomat®, an actuated exoskeleton that guide the patient's limbs, simulating a symmetrical bilateral gait. Preliminary evidence suggests that beyond gait parameters, robotic assisted gait training may also improve balance. Therefore, the aim of this systematic review was to summarize evidence about the effectiveness of Lokomat® in improving balance in stroke patients.Methods: Randomized controlled trials published between January 1989 and August 2020, comparing Lokomat® training to conventional therapy for stroke patients, were retrieved from seven electronic databases. Balance, assessed by means of validated clinical scales, was considered as outcome measure. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality of the studies. The study protocol was registered on PROSPERO (no. CRD42020197531).Results: After the removal of the duplicates, according to the inclusion criteria, 13 studies were selected, involving 445 subacute or chronic stroke patients. Eleven papers contributed to three meta-analyses. Favorable results for recovery of balance in stroke survivors treated with Lokomat® were shown using Timed Up and Go (pooled mean difference = −3.40, 95% CI −4.35 to −2.44; p < 0.00001) and Rivermead Mobility Index as outcome measures (pooled mean difference = 0.40, 95% CI 0.26–0.55; p < 0.00001). Inconclusive results were found when balance was measured by means of the Berg Balance Scale (pooled mean difference = 0.17, 95% CI −0.26 to 0.60; p = 0.44).Conclusions: Overall, most studies have shown beneficial effects of Lokomat® on balance recovery for stroke survivors, at least comparable to conventional physical therapy. However, due to the limited number of studies and their high heterogeneity, further research is needed to draw more solid and definitive conclusions.

The QTc interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. This marker is often prolonged in acute and chronic neurological conditions. The cause of the cerebrogenic QT prolongation remains unclear. The aim of the study was to analyze the relation between QTc interval and the degree of cognitive impairment and structural brain imaging changes in patients with dementia and mild cognitive impairment (MCI). To this aim, 269 patients were screened, of whom 61 met one or more exclusion criteria. The remaining 208 patients (56 control subjects, 44 patients with MCI, and 108 with dementia) were recruited. Eighty-five patients using drugs causing prolongation of QT interval were further excluded. The QT interval was measured manually in all 12 leads by a single blinded observer, assuming the longest QT value adjusted for heart rate by using the Bazett's formula. All patients underwent a structural brain imaging and the following measures were obtained: the bicaudate ratio and the periventricular hyperintensity and deep white matter hyperintensity using the modified Fazekas scale. Prolonged QTc interval was prevalent in 1) patients with dementia, especially in those with moderate-severe degree; 2) subjects with impairment of praxis and attention, low functional status, and behavioral symptoms; 3) patients with global and temporal atrophy and with higher scores on the Fazekas or leukoaraiosis scales. Degenerative and vascular processes might play a main role in QTc interval prolongation because of the damage to brain areas involved in the control of the autonomic cardiac nervous system.

Background The progressive aging of the population will dramatically increase the burden of dementia related to Alzheimer's disease (AD) and other neurodegenerative disorders in the future. Because of the absence of drugs that can modify the neuropathological substrate of AD, research is focusing on the application of preemptive and disease-modifying strategies in the pre-symptomatic period of the disease. In this perspective, the identification of people with cognitive frailty (CF), i.e., those individuals with higher risk of developing dementia, on solid pathophysiological bases and with clear operational clinical criteria is of paramount importance. Objective/methods This hypothesis paper reviews the current definitions of CF, presents and discusses some of their limitations, and proposes a framework for updating and improving the conceptual and operational definition of the CF construct. Results The potential for reversibility of CF should be supported by the assessment of amyloid, tau, and neuronal damage biomarkers, especially in younger patients. Physical and cognitive components of frailty should be considered as separate entities, instead of part of a single macro-phenotype. CF should not be limited to the geriatric population, because trajectories of amyloid accumulation are supposed to start earlier than 65 years in AD. Operational criteria are needed to standardize assessment of CF. Conclusion Based on the limitations of current CF definitions, we propose a revised one according to a multidimensional subtyping. This new definition might help stratifying CF patients for future trials to explore new lifestyle interventions or disease-modifying pharmacological strategies for AD and dementia.

Introduction Preliminary evidences showed that telemedicine may allow a reduction of costs and an enhancement of patients’ satisfaction and quality of life (QoL), with the same effectiveness of conventional methods of healthcare delivery. Literature is quite absent in relation to the use of telemedicine for patients with disorders of consciousness (DoC) whose management is delegated almost entirely to the family. In order to promote an alternative setting to manage persons affected by DoC, also supporting their families, a pilot project was designed to test the feasibility of home-care assistance based on a system of telemonitoring. Methods In total, 11 patients were supported by a telemonitoring system via a workstation installed at the patients’ homes. All patients underwent a clinical and functional evaluation at enrolment, after two months, after six months and at the end of the project, after 12 months by means of clinical scales (Glasgow Coma Scale, Rancho Los Amigos Levels of Cognitive Functioning Scale, Glasgow Outcome Scale, Disability Rating Scale), while the World Health Organization (WHO) QoL, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale and a satisfaction score were completed by caregivers. Results Patients’ scores at the clinical scales did not show statistically significant differences from T0 to T3. A trend toward the improvement of caregivers’ QoL, anxiety and depression, as well as a high degree of satisfaction with regard to the intervention, were reported. The economic evaluation showed an average cost/day for a patient of about €70. Discussion Preliminary data suggest that the use of telemonitoring services in the management of persons affected by DoC is feasible and well accepted by caregivers, with a potential positive effect on their mood and QoL. Therefore, telemonitoring should be considered in the management of DoC patients to favour discharge from acute care and to support families in home care.

Background Few studies have investigated the effect of vitamin E in reducing the cisplatin (CDDP)-induced ototoxicity. This study evaluated vitamin E supplementation as a protecting agent against CDDP-induced ototoxicity. Methods Patients who started CDDP were randomly assigned to receive vitamin E supplementation at 400 mg per day (group 1) or placebo (group 2). Audiograms and evoked brainstem responses were obtained at baseline, and after 1, 2, and 3 months. Results Twenty-three patients affected by solid malignancies were enrolled (13 in group 1 and 10 in group 2). At 1 month, a significant hearing loss in group 2 at both 2000 HZ (right ear: p = .05; left ear: p = .04) and 8000 HZ (right ear: p = .04; left ear: p = .03) was detected when compared to baseline values. Audiograms did not show significant changes. At 1 month, evoked brainstem responses remained unchanged in both arms without significant differences between groups. Conclusion These preliminary findings confirm the neuroprotective properties of vitamin E against the CDDP-induced ototoxicity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2118–E2121, 2016

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor in adults, with an increasing incidence in patients aged 75 through 85. Prognosis in these patients is particularly dismal due to more aggressive tumor biology, lower functional reserve and high prevalence of comorbidities. Many studies report cognitive impairment in GBM patients, ranging from 29 to 90%. This study was aimed at evaluating neurocognitive status and comorbidities of an elderly population with high grade glioma and the correlation with clinical and demographical variables. METHODS: Patients underwent an extended neuropsychological evaluation with a battery of standardized tests on 8 cognitive domains: global function (GF); verbal learning (VL); short and long-term memory (STM); executive functions (EF); abstract reasoning (AR); attention (ATT) and visuo-constructional abilities (CA). Moreover, the Cumulative Illness Rating Scale was administered to each patient for comorbidities evaluation. RESULTS: We assessed 69 patients with median age at diagnosis of 74 years (range 65–85). 43 patients (62%) presented multi-domain cognitive impairment, and only 8 (12%) showed no cognitive impairment. Neuropsychological deficit mainly affected executive functions (n=42), short term memory (n=28), long term memory and attention (n=22). Patients with AR deficit had a poorer PFS and OS (p

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor in adults, with an increasing incidence in patients aged 75 through 85. Prognosis in these patients is particularly dismal due to more aggressive tumor biology, lower functional reserve and high prevalence of comorbidities. Many studies report cognitive impairment in GBM patients, ranging from 29 to 90%. This study was aimed at evaluating neurocognitive status and comorbidities of an elderly population with high grade glioma and the correlation with clinical and demographical variables. MATERIAL AND METHODS: patients underwent an extended neuropsychological evaluation with a battery of standardized tests on 8 cognitive domains: global function (GF); verbal learning (VL); short and long-term memory (STM); executive functions (EF); abstract reasoning (AR); attention (ATT) and visuo-constructional abilities (CA). Moreover, the Cumulative Illness Rating Scale was administered to each patient for comorbidities evaluation. RESULTS: We assessed 69 patients with median age at diagnosis of 74 years (range 65–85). 43 patients (62%) presented multi-domain cognitive impairment, and only 8 (12%) showed no cognitive impairment. Neuropsychological deficit mainly affected executive functions (n=42), short term memory (n=28), long term memory and attention (n=22). Patients with AR deficit had a poorer PFS and OS (p

Neuropsychological testing is a key diagnostic tool for assessing people with dementia and mild cognitive impairment, but can also help in other neurological conditions such as Parkinson’s disease, stroke, multiple sclerosis, traumatic brain injury and epilepsy. While cognitive screening tests offer gross information, detailed neuropsychological evaluation can provide data on different cognitive domains (visuospatial function, memory, attention, executive function, language and praxis) as well as neuropsychiatric and behavioural features. We should regard neuropsychological testing as an extension of the neurological examination applied to higher order cortical function, since each cognitive domain has an anatomical substrate. Ideally, neurologists should discuss the indications and results of neuropsychological assessment with a clinical neuropsychologist. This paper summarises the rationale, indications, main features, most common tests and pitfalls in neuropsychological evaluation.

BACKGROUND Considering the demographic trend, characterized by a marked aging due to the increase in life expectancy and the improvement in medical care, in the next future elderly patients will represent the majority of stroke victims with a strong impact on rehabilitative services. AIM To investigate and characterize differences in functional outcome in elderly patients after stroke. DESIGN Observational study. SETTING Post-acute inpatient rehabilitation. POPULATION Subjects aged ≥65 years with acute (i.e. within 30 days from onset) ischemic or hemorrhagic stroke. METHODS At admission, all patients underwent neurological and clinical examination, functional evaluation and laboratory assessment. Comorbidities and clinical complications during hospital stay were recorded. Functional status was evaluated by means of the Functional Independence Measure (FIM) administered at admission and discharge. All patients underwent neuromotor rehabilitation, and speech therapy in case of aphasia, once a day, six days per week. RESULTS The study enrolled 402 patients, who were stratified in three groups according to age: 145 patients in Group 1, the young-old (65-74.9 years, G1), 206 in Group 2, the middle-old (75-84.9 years, G2) and 51 in Group 3, the oldest-old (≥85 years, G3). At discharge, FIM total scores increased significantly for all the groups (P

Introduction Selegiline ( l -deprenyl) is a selective monoamine oxidase type B inhibitor that has been shown to have neurotrophic and anti-apoptotic properties and to protect neurons in different experimental models of cerebral ischaemia. The aim of this explorative study was to investigate whether selegiline could enhance cognitive and functional recovery in stroke survivors. Methods This was a randomized controlled study in which patients enrolled within two weeks of stroke underwent a clinical and functional evaluation and a neuropsychological assessment. The patients were given selegiline (10 mg/day) or matched placebo once a day for six weeks in addition to standard rehabilitation care. Results Of 137 stroke survivors, 47 patients met the inclusion criteria and were randomly assigned to the Study Group (n = 23) or the Control Group (n = 24). The statistical analysis showed a significant improvement in most neuropsychological tests after two and six weeks in the study group; these improvements were not replicated in the control group. The between-group analysis revealed that the domains of attention and executive functions benefited most from the drug treatment. With regard to functional status, comparison of clinical scores at admission and discharge showed a statistically significant enhancement in both groups without statistically significant differences between the groups. Conclusions These preliminary results suggest that selegiline administered in the subacute phase can promote cognitive functioning in stroke patients. Further studies will elucidate whether and how this enhancement can impact on functional recovery in the short and in the long term.

Study objectives To investigate the capacity of neuropsychological deficits in idiopathic rapid eye movement sleep behavior disorder (iRBD) to predict the development of dementia and/or parkinsonism. Design Prospective longitudinal follow-up study. Setting Tertiary sleep center. Patients Twenty patients with initial iRBD (19 males, mean age 66.1 ± 7.1) underwent a clinical and neuropsychological follow-up within a mean of 43 ± 19 months. Neuropsychological performances at baseline were compared with those of healthy controls matched for sex, age, and education. Interventions Discontinuation of clonazepam at least 7 days before the follow-up evaluation. Results At follow-up, the Wilcoxon test showed a significant worsening of scores on Raven Colored Matrices 47 (P = 0.01), Attentive matrices (P = 0.002), phonemic (P = 0.04) and sematic (P = 0.04) fluency. Thirteen patients (65%) showed cognitive deterioration involving multiple domains. Of these, four patients (20%) maintained a stable cognitive dysfunction and nine (45%) showed a progression of cognitive dysfunction: six (30%) in constructional abilities (P = 0.03), four (20%) in short-term memory (P = NS), three (15%) in executive functions and non-verbal logic (P = NS), one (5%) in verbal fluency (P = NS), and one (5%) in long-term memory (P = NS) (McNemar test). Seven patients (35%) retained a normal cognitive profile. Mild cognitive impairment (MCI) was diagnosed at baseline in seven patients (35%). At follow-up, three of these patients showed overt dementia that was accompanied by parkinsonism in all cases; one had worsened from non-amnesic single-domain to nonamnesic multiple-domain MCI, two were stable, and one patient no longer met the criteria for MCI. Four patients (20%) without MCI at baseline had MCI at follow-up. Patients who developed MCI/dementia had an older age at disease onset (65.8 ± 5.4 versus 56.8 ± 9.3; P = 0.01) compared with those who did not. Conclusions Our findings corroborate evidence that visuospatial abilities constitute the area most affected in idiopathic rapid eye movement sleep behavior disorder (learning as a stable deficit and copying as an evolving deficit). Cognitive deterioration, involving mainly nonverbal logic, attention, and executive functions, can be observed in rapid eye movement sleep behavior disorder follow-up, suggesting an underlying evolving degenerative process. Our data confirm that mild cognitive impairment is frequent in idiopathic rapid eye movement sleep behavior disorder. The presence of mild cognitive impairment predicts the eventual risk of developing dementia, which seemed to be associated with parkinsonism.

Brain tumors and anti-cancer treatments can cause a wide range of cognitive deficits that in turn, being a major cause of disability, significantly affect patients' independence and quality of life. To evaluate the neurocognitive status of a non selected population of brain tumors outpatients, investigating the correlation with clinical and demographic variables. This prospective cross-sectional survey enrolled consecutive outpatients with a histopathologically confirmed diagnosis of brain tumor. All the patients were evaluated with a battery of standardized neuropsychological tests assessing language, memory, logical-executive functions, attention, visuo-constructional abilities. An univariate regression analysis was performed to assess the impact of socio-demographical and clinical variables on the presence of cognitive impairment. 147 patients (61F/86M, mean age 52.8 ± 13.3, mean schooling 12.7 ± 4 were enrolled into the study. Out of the 147 patients evaluated, 80 (54.4 %) showed cognitive impairment: 43 (53.75 %) presented a multidomain impairment, while 37 (46.25 %) patients revealed cognitive deficits limited respectively to language (n:13, 16.25 %), memory (n:11, 13.75 %), attention (n:7, 8.75 %), logical-executive functions (n:5, 6.25 %), visuo-spatial abilities (n:1, 1.25 %). At the regression analysis the variables significantly related to the development of cognitive impairment were age (p = 0.04), lesion side (p = 0.00), chemotherapy (p = 0.03). As advances in anti-cancer treatment have prolonged life expectancy of neuro-oncological patients, standard clinical endpoints can't be limited to just survival or progression free survival, but have to consider clinical benefits on both motor and cognitive function and in general quality of life. Hence evaluation of new therapeutic strategies should routinely include longitudinal neuropsychological assessment.

The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD). Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients’ functional competence. A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9

Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients, linked with morbidity, disability, and poor quality of life. As pharmacologic interventions have not yet proven effective in the treatment of cognitive deficits, cognitive rehabilitation could represent an alternative approach. This paper presents three case studies, describing the cognitive intervention and discussing its effectiveness in the light of current evidence.

Background and aims: Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist. Clinical and observational studies have demonstrated its efficacy on both cognitive and behavioral symptoms of moderate-to-severe Alzheimer’s disease (AD) and described its good safety and tolerability profile. We report here our experience with memantine in patients with AD during a two-year follow-up. Methods: From June 2005 to May 2010, memantine was given to 201 outpatients with moderate-to-severe AD: 93 patients were concomitantly receiving treatment with acetyl cholinesterase inhibitors (AChEIs) (Group 1) and the other 108 were prescribed memantine as monotherapy (Group 2). All patients were administered the following scales: Mini Mental State Examination, Activities of Daily Living, Instrumental Activities of Daily Living, Neuropsychiatric Inventory. We report the results of followup assessments conducted at six months and 1, 2 and 3 years. Results: Sixteen patients (8%) stopped treatment within the first month because of side-effects. In each group, about 20% of subjects showed no deterioration at six months and 1 year, and this proportion decreased only slightly at 2 years. Higher NPI scores at baseline and psychotropic drug use emerged as factors significantly related to reduced response to treatment (p

This study was set out to describe caregiver-perceived burden and coping in early-stage Alzheimer disease (AD). A total of 163 consecutive pairs of patients with AD and their principal caregivers were initially recruited. The caregivers completed the Caregiver Burden Inventory (CBI) and the Coping Orientations to Problems Experienced scale, and also provided sociodemographic information; the patients with AD were assessed by means of the Mini Mental State Examination and the Neuropsychiatric Inventory. Data from 126 patient-caregiver pairs were analyzed. The caregivers (mean age 56.11±12.37 y) were mainly women (76%); 64% were the patient's offspring; 39% lived with the patient. From the CBI data, it emerged that caregivers perceived loss of personal time (objective burden, 33%) and the feeling of missing out on opportunities (developmental burden, 25%) as their main stressors. Total CBI score was negatively correlated with Mini Mental State Examination (P=0.005). As regards coping strategies, the caregivers predominantly used problem-oriented strategies associated with a positive attitude. The use of dysfunctional strategies was predictive of caregiver burden. It is important to be aware that avoidance and dysfunctional coping strategies predispose caregivers of patients with AD to higher level of distress, whereas successful caregiving seems to be based on the use of problem-oriented strategies early in the disease when solutions are still available.

Alien hand syndrome is a rare neurological disorder characterized by involuntary and uncontrollable motor behaviour, usually of an arm or hand. The patient perceives the affected limb as alien, and may personify it. The case of a 61-year-old right-handed woman who developed right posterior AHS after ischaemic stroke in the left posterior cerebral artery territory is reported. Neuroimaging studies disclosed no frontal or parietal involvement, while a posterior thalamic lesion was detected. A possible role of the thalamus in the genesis of AHS is discussed.

Background Rapid eye movement [REM] sleep behaviour disorder (RBD) may herald neurodegenerative diseases. Neurobiological deficits similar to those identified in neurodegenerative diseases have been reported in idiopathic RBD. Researchers are looking for early markers supporting a possible role of RBD as a harbinger of impending neurodegenerative disease. Objective To examine the neuropsychological functions in idiopathic RBD subjects. Should they be found to present a neuropsychological dysfunction that overlaps that reported in neurodegenerative diseases, it would be possible to consider cognitive deficits as possible early markers of an underlying degenerative process. Methods Twenty-three subjects with idiopathic RBD (21 males, mean age 67.0±7.0 years) and a group of healthy controls matched for sex, age and education underwent a neuropsychological battery evaluating different cognitive domains. Findings Considering mean values, poorer performances were observed in the Word Span ( p p =.003), Digit Span ( p =.003) and Logic Memory ( p =.003) tests. On the basis of equivalent scores, the RBD subjects performed significantly more poorly on tests of visuo-constructional learning abilities ( p Interpretation Our data show the possible presence of cognitive deficits in RBD defined as idiopathic, sharing common features in particular with Lewy body disease. Neuropsychological evaluation in RBD could lead to presymptomatic identification of neurodegenerative disease, but until more prolonged long-term follow-up data are available, the true neurobiological significance of cognitive deficits in RBD will remain unknown.

The aim of this study was to individuate different clinical and cognitive pictures among non-demented subjects reporting cognitive disturbances. We evaluated 75 subjects referring to Alzheimer's Disease Assessment Unit of IRCCS C. Mondino, Pavia, who complained memory disturbances in absence of impairment in every day activities, not fitting DSM-IV criteria for dementia (MMSE > 24). The subjects underwent neurological examination, blood chemistry and neuroimaging. The neuropsychological evaluation included tests exploring language, short- and long-term memories, logical abilities, attentive and visuo-constructional functions. Fifty-two patients fitted the criteria for mild cognitive impairment (MCI); twenty-three subjects had a neuropsychological evaluation within normal range for age and schooling; they were significantly younger and better educated and presented higher scores at scale for depression and anxiety than the MCI patients. In the MCI group, on the basis of cognitive profile and neuroimaging, different subtypes could be distinguished. Subjective cognitive complaints represent a heterogeneous condition, which can develop into different clinical pictures. It is, therefore, important to individuate specific clinic and neuropsychological profiles, possible predictive of different evolution.

Few studies have investigated the effect of vitamin E in reducing the cisplatin (CDDP)-induced ototoxicity. This study evaluated vitamin E supplementation as a protecting agent against CDDP-induced ototoxicity.Patients who started CDDP were randomly assigned to receive vitamin E supplementation at 400 mg per day (group 1) or placebo (group 2). Audiograms and evoked brainstem responses were obtained at baseline, and after 1, 2, and 3 months.Twenty-three patients affected by solid malignancies were enrolled (13 in group 1 and 10 in group 2). At 1 month, a significant hearing loss in group 2 at both 2000 HZ (right ear: p = .05; left ear: p = .04) and 8000 HZ (right ear: p = .04; left ear: p = .03) was detected when compared to baseline values. Audiograms did not show significant changes. At 1 month, evoked brainstem responses remained unchanged in both arms without significant differences between groups.These preliminary findings confirm the neuroprotective properties of vitamin E against the CDDP-induced ototoxicity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2118-E2121, 2016.

The management of elderly glioblastoma (GBM) remains controversial for under-representation in controlled trials, for modest tolerance of treatments, and higher rate of side effects. Age was identified as an important prognostic factor for survival, mainly in patients with poor performance status. The presence of co-morbidities (CM) represents an important issue in elderly because the correlation with frailty, and the role as predictor of disability and mortality. The aim of this study was to evaluate the impact of CM on outcome of elderly GBM. METHODS: Patients affected by GBM with age ≥ 65 years have been enrolled in a prospective study. For each patient, CM were identified with the Cumulative Illness Rating Scale (CIRS). RESULTS: Sixty-six elderly patients affected by GBM were enrolled into the study. The average age at diagnosis was 73 years (range 65-87). The median PFS at 12 months has been 8 months, with a rate of 29.1% patients free of progression at 1 year. The median OS has been 18 months (95% CI 13-23), with a survival rate of 35% at 2 years. The univariate analysis showed that the severity of CM is a strong predictor of disease progression (HR = 1.24, 95% CIs from 1.11 to 1.38, p = 0.000). Multivariate analysis confirmed that the severity of CM (HR = 1.24 for each increase of CIRS score, 95% CIs from 1.11 to 1.38, p = 0.000) is an independent predictor of disease progression. In addition, higher score of CM and age higher than 75 years are associated with short survival. DISCUSSION: We observed that high CM score is an independent predictor of disease progression and shorter survival. The evaluation of CM should drive therapeutic decisions in elderly GBM. In subgroups of elderly GBM without high score of CM, standard treatments should be considered. Further studies on elderly GBM are warranted to confirm these data.

Cognitive rehabilitation is usually administered in form of paper-based exercises the patient is required to solve. With the availability of new and advanced technologies, computer science is gaining more and more importance in the treatment routine. In this paper a software system for the rehabilitation of cognitively impaired subjects will be presented. Its features guarantee many advantages, both for patients and therapists, but to prevent the risk of reduced compliance, which, considering the intended target of the system- typically elderly people with low computer skills- cannot be ignored, 3D technology has been introduced. The project choices made and implementation strategies applied to increase immersion and entertainment and prevent boredom and drops in compliance will be described. Open issues and future works will also be illustrated.

This work aims at providing a tool for supporting cognitive rehabilitation. This is a wide field, that includes a variety of diseases and related clinical pictures; for this reason the need arises to have a tool available that overcomes the difficulties entailed by what currently is the most common approach, that is, the so-called pen and paper rehabilitation.We first organized a big number of stimuli in an ontology that represents concepts, attributes and a set of relationships among concepts. Stimuli may be words, sounds, 2D and 3D images. Then, we developed an engine that automatically generates exercises by exploiting that ontology. The design of exercises has been carried on in synergy with neuropsychologists and speech therapists. Solutions have been devised aimed at personalizing the exercises according to both patients' preferences and performance.Exercises addressed to rehabilitation of executive functions and aphasia-related diseases have been implemented. The system has been tested on both healthy volunteers (n = 38) and patients (n = 9), obtaining a favourable rating and suggestions for improvements.We created a tool able to automate the execution of cognitive rehabilitation tasks. We hope the variety and personalization of exercises will allow to increase compliance, particularly from elderly people, usually neither familiar with technology nor particularly willing to rely on it. The next step involves the creation of a telerehabilitation tool, to allow therapy sessions to be undergone from home, thus guaranteeing continuity of care and advantages in terms of time and costs for the patients and the National Healthcare System (NHS). Implications for rehabilitation Cognitive impairments can greatly impact an individual's existence, appreciably reducing his abilities and autonomy, as well as sensibly lowering his quality of life. Cognitive rehabilitation can be used to restore lost brain function or slow down degenerative diseases. Computerization of rehabilitation entails many advantages, but patients - especially elderly people - might be less prone to the use of technology and consequently reluctant towards this innovative therapeutic approach. Our software system, CoRe, supports a therapist during the administration of rehabilitation sessions: exercises can be generated dynamically, thus reducing repetitivity, and patients' performance trends automatically analysed to facilitate the assessment of their progress. Tests performed on both healthy subjects and patients provided useful information that allowed us to define an implementation strategy able to reduce patients' resistance to computerized rehabilitation as much as possible.

Sleep disorders can occur in many neurodegenerative disorders; in a previous paper we constructed a scale investigating sleep discontinuity/fragmentation with the aim to obtain a rapidly and easily administered tool suitable for early identification and longitudinal monitoring of sleep disturbances in Alzheimer's disease (AD). We introduced this instrument in the daily clinical practice in a center for dementia; here we present the results of our experience. Two hundred and sixteen AD outpatients referred to the Alzheimer's Disease Assessment Unit at the IRCCS C. Mondino National Neurological Institute, Pavia, Italy, in the period October 2012 to March 2014 were administered the scale. The questionnaire global score was correlated with measures of cognitive, functional and behavioral impairment; a significant association was found with Mini-Mental State (p = 0.005), Activities of Daily Living (p = 0.01), Neuropsychiatric Inventory (p = 0.01) and Clinical Dementia Rating (p = 0.0005). The present data indicate that the previously validated questionnaire proves to be a suitable, rapid and easy to use tool in investigating sleep quality in AD in daily clinical practice. An early identification and longitudinal monitoring of sleep disturbances in AD may improve pharmacological and non-pharmacological interventions.

Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.

Smart Aging, a Serious games (SGs) platform in a 3D virtual environment aimed at the early detection of Mild Cognitive Impairments (MCI) in persons ageing between 50 and 80. The navigation in a 3D environment (loft) that simulates in a reduced space the basic elements of interaction of home living, associated with the game approach results in a powerful screening tool, more friendly and motivating with respect to the traditional paper&pencil tests. The Smart Aging platform asks people to perform tasks related to daily activities, closer to real life than traditional paper&pencil tests, and, in doing so, it is able to evaluate different cognitive functions. The platform has been realized through a strong collaboration between game developers, neurologists and neuropsychologists. A scientific validation phase is ongoing on a sample of 1000 users to provide evidence of the efficacy and usefulness of the Smart Aging system.

Background Acute ischemic stroke (AIS) is influenced by gender, age, and the brain site affected. Better characterization of AIS is necessary for improving guidelines, prevention, and destination of resources. Methods Demographics, prestroke conditions, etiology, subtypes, specific hospital outcome, clinical and laboratory parameters, and mortality rates were prospectively registered in 105 southern Italian patients. Results AIS became more frequent in women than in men after age 65 years. Cryptogenic AIS decreased with age independently of sex and lesion site. Cerebellum–brainstem stroke was more prevalent in men, whereas anterior AIS was more frequent in women. There were no overall differences in 6- and 12-month survival rates based on site or sex; however, mortality rates were high after age 80 years. Chronic kidney disease was more frequent in patients with cerebellum–brainstem stroke, and its prevalence increased significantly with age independently of sex. Association of AIS with arterial hypertension, diabetes, and previous myocardial infarction increased with age, whereas that with active smoking decreased with age, independently of sex and site. Conclusion Specific AIS etiology and blood characteristics associated independently to the youngest and oldest AIS patients, respectively. Chronic kidney disease was a specific predictor of cerebellum–brainstem AIS. AIS mortality showed peculiar association with the oldest patients.

Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients and exerts a deep negative impact on quality of life interfering with familiar, social and career-related activities. To test the effectiveness of early cognitive rehabilitation treatment for inpatients affected by primary brain tumors. Out of 109 consecutive patients enrolled in the study, 58 patients were randomly assigned to a rehabilitation group or to a control group. The rehabilitation consisted of 16 one-hour individual sessions of therapist-guided cognitive training, spread over 4 weeks, combining computer exercises and metacognitive training. Patients in the control group received usual care without cognitive training. All patients were evaluated by means of a comprehensive neuropsychological battery at the admission (T0) and after 4 weeks (T1). Patients in the rehabilitation group showed a significant improvement of cognitive functions. In particular, the domains that benefited most from the training were visual attention and verbal memory. The control group exhibited only a slightly, not statistically relevant, enhancement of cognitive performances. Cognitive rehabilitation for neuro-oncological inpatients resulted in a significant enhancement of cognitive performances after the training, also providing a foundation for early administration. Future research should be aimed to clarify the patients’ characteristics that predict neuropsychological improvement, to identify the most effective elements in rehabilitative programs and to study the effects of treatment extension to everyday life.

Chiara Zucchella,1 Elena Sinforiani,1 Antonietta Citterio,1 Valentina Giarracca,2 Giorgio Bono,2 Marco Mauri21IRCCS National Neurological Institute, C Mondino Foundation, Pavia, Italy; 2Department of Neurology, Ospedale di Circolo/Università dell’Insubria, Varese, ItalyAbstract: The aim of our study was to understand the complex relationship between the major reproductive life events in women with Alzheimer’s disease. In a retrospective, case-control study, 275 women with Alzheimer’s disease (AD) and 276 control patients from a hospital population were enrolled from July 2007 to December 2010. The AD patients presented with later menopause (P < 0.01), lower occurrence of surgical menopause (P < 0.04), reduced hormone-replacement therapy intake (P < 0.0001), and a longer reproductive life span (P < 0.01), compared to controls. No significant differences were found with respect to age at puberty, number of pregnancies, previous abortions, or contraceptive therapy. A higher education level appeared to have a protective role against the risk of developing AD. In women, menopause and hormone-replacement therapy can differentially modulate the clinical manifestations of AD, but these factors do not play a predictive role in its development.Keywords: Alzheimer’s disease, gender, menopause, hormone-replacement therapy, surgical menopause, education

A considerable proportion of subjects initially diagnosed with idiopathic REM sleep behavior disorder (iRBD) are reported to convert to a neurodegenerative disorder, mainly synucleinopathies. It is unclear whether cognitive deficits in iRBD represent an associated feature or a marker predictive of subsequent development of a synucleinopathy. Cross-sectional studies indicate that a proportion of iRBD patients show cognitive deficits similar to those typically found in patients with synucleinopathies. The available longitudinal data suggest that cognitive dysfunction in iRBD tends to progress over time, with this progression probably being underpinned by a neurodegenerative process. Furthermore, within the framework of Parkinson's disease, RBD has been shown to be a risk factor for progressive cognitive decline even advancing to dementia. This paper addresses the multifaceted issue of cognitive dysfunction in RBD. Taking into account some key literature findings and preliminary longitudinal observations of our own, it shows that cognitive deterioration, mainly involving visuospatial abilities (learning as a stable deficit and copying as an evolving deficit), non-verbal logic, attention and executive functions can be observed in iRBD follow-up, suggesting an underlying evolving degenerative process. Large cohort studies with more prolonged follow-ups and greater methodological uniformity are needed to provide more reliable and robust findings.