Neurorehabilitation in brain tumours: evidences and suggestions for spreading of knowledge and research implementation.

PURPOSE OF REVIEW: The last few decades have seen an increase in life expectancy in brain tumour patients; however, many patients report sensory-motor and cognitive disabilities due to the tumour itself, but also to the effect of anticancer treatments (surgery, radiotherapy, chemotherapy), supportive treatments, as well as individual patient factors. This review outlines the principles on which to base neurorehabilitation treatments, with the aim of stimulating an early rehabilitative management, in order to reduce disability and functional limitation and improve the quality of life of the persons affected by brain tumour. RECENT FINDINGS: Although not definitive, evidences suggest that an early neurorehabilitative evaluation, performed with a multidisciplinary approach, may identify the different functional impairments that can affect people with brain tumour. Furthermore, identifying and classifying the person's level of functioning is useful for designing achievable recovery goals, through the implementation of tailored multidisciplinary rehabilitation programs. The involvement of different professional figures allows to treat all the components (physical, cognitive, psychological and participation) of the person, and to redesign one's life project, lastly improving the quality of life. SUMMARY: Overall, the evidences suggest a critical need for the development of this clinical area by spreading the concept of rehabilitation among neuro-oncologists and producing high quality research.

Factors influencing cognitive performance after 1-year treatment with direct oral anticoagulant in patients with atrial fibrillation and previous ischemic stroke: a pilot study.

Anticoagulant treatment as stroke prevention, particularly direct oral anticoagulant (DOAC), may reduce the risk of dementia in patients with atrial fibrillation (AF). We aimed to assess factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. We recruited 33 ischemic stroke patients who were discharged from Verona Stroke Unit with diagnosis of AF and prescription of treatment with DOAC. For each cognitive test, we estimated the effect of T0 (first session) variables on T1 (1-year session) cognitive performance using ordinal logistic regression fitted to a 1 point-shift from 4 to 0 on ESs. The effect of T0 clinical variables was presented as odds ratio (OR) with 95% confidence interval (CI) after adjustment for T0 total score of the corresponding cognitive test. Sustained AF (OR: 4.259, 95% CI 1.071-16.942) and ischemic heart disease (OR: 6.654, 95% CI 1.329-33.300) showed a significant effect on T1 MoCA Test; congestive heart failure on T1 RAVLT Immediate recall (OR: 9.128, 95% CI 1.055-78.995), T1 RAVLT Delayed recall (OR: 7.134, 95% CI 1.214-52.760), and T1 Trail Making Test (Part A) (OR: 16.989, 95% CI 1.765-163.565); sustained AF (OR: 5.055, 95% CI 1.224-20.878) and hyperlipidemia (OR: 4.764, 95% CI 1.175-19.310) on T1 Digit span forward Test; ischemic heart disease (aOR: 8.460, 95% CI 1.364-52.471) on T1 Stroop Color and Word Test (time); Dabigatran use (aOR: 0.084, 95% CI 0.013-0.544) on FAB; age ≥ 75 years (aOR: 0.058, 95% CI 0.006-0.563) and hyperlipidemia (aOR: 5.809, 95% CI 1.059-31.870) on T1 Phonemic word fluency Test; female sex (aOR: 6.105, 95% CI 1.146-32.519), hyperlipidemia (aOR: 21.099, 95% CI 2.773-160.564), total Modified Fazekas Scale score > 1 (aOR: 78.530, 95% CI 3.131-1969.512) on Semantic word fluency Test. Sustained AF, ischemic heart disease, congestive heart failure, hyperlipidemia, and female sex were the factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. Modified Fazekas Scale score in the first session was the only radiological variable that had a significant effect on cognitive performance.

Comorbidities in elderly patients with glioblastoma: a field-practice study.

AIM: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM). PATIENTS & METHODS: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS). RESULTS:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival. CONCLUSION: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.

Neuropsychological testing.

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.

Modeling Alzheimer Disease Through Functional Independence and Participation.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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; <10) that were compared. The statistical analysis revealed that all the cognitive domains were positively related to functional independence, but only logical and executive functions seemed to predict autonomy. An intergroup comparison did not show significant differences in the DAD subscales measuring initiation, planning and organization, and performance. The role of education emerged, confirming the relevance of cognitive reserve. DISCUSSION: As the field moves toward earlier intervention in preclinical AD, the detection of early functional changes may drive the definition of trials on prevention or intervention for dementia.

Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.

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.

A wearable system for visual cueing gait rehabilitation in Parkinson's disease: a randomized non-inferiority trial.

BACKGROUND: Gait disturbances represent one of the most disabling features of Parkinson's disease (PD). AIM: The aim of this study was to evaluate the non-inferiority of a new wearable visual cueing system (Q-Walk) for gait rehabilitation in PD subjects, compared to traditional visual cues (stripes on the floor). DESIGN: Open-label, monocentric, randomized controlled non-inferiority trial. SETTING: Outpatients. POPULATION: Patients affected by idiopathic PD without cognitive impairment, Hoehn and Yahr stage II-IV, Unified Parkinson's Disease Rating Scale motor section III ≥2, stable drug usage since at least 3 weeks. METHODS: At the enrollment (T0), all subjects underwent a clinical/functional evaluation and the instrumental gait and postural analysis; then they were randomly assigned to the Study Group (SG) or Control Group (CG). Rehabilitation program consisted in 10 consecutive individual sessions (5 sessions/week for 2 consecutive weeks). Each session included 60 minutes of conventional physiotherapy plus 30 minutes of gait training by Q-Walk (SG) or by traditional visual cues (CG). Follow-up visits were scheduled at the end of the treatment (T1) and after 3 months (T2). RESULTS: Fifty-two subjects were enrolled in the study, 26 in each group. The within-groups analysis showed a significant improvement in clinical scales and instrumental data at T1 and at T2, compared to baseline, in both groups. According to the between-group analysis, Q-Walk cueing system was not-inferior to the traditional cues for gait rehabilitation. The satisfaction questionnaire revealed that most subjects described the Q-Walk cueing system as simple, motivating and easily usable, possibly suitable for home use. CONCLUSIONS: Data showed that motor rehabilitation of PD subjects performed by means of the new wearable Q-Walk cueing system was feasible and as effective as traditional cues in improving gait parameters and balance. CLINICAL REHABILITATION IMPACT: Wearable devices can act as an additional rehabilitation strategy for long-term and continuous care, allowing patients to train intensively and extensively in household settings, favoring a tailor-made and personalized approach as well as remote monitoring.

Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data.

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data. Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review. Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature. Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.

Cognitive impairment in primary brain tumors outpatients: a prospective cross-sectional survey.

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.

Cognitive rehabilitation for early post-surgery inpatients affected by primary brain tumor: a randomized, controlled trial.

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.

Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson's disease: current evidence and future perspectives.

INTRODUCTION: Non-motor symptoms (NMS) affect patients with Parkinson's disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients' and caregivers' quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need. AREAS COVERED: The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies. EXPERT OPINION: The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer's disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers.

Early rehabilitation after surgery improves functional outcome in inpatients with brain tumours.

Clinical experience suggests that application of the fundamental principles of rehabilitation medicine can improve the care of patients with cancer. Despite the high incidence of neurological and functional deficits in patients affected by brain tumours (BTs), rehabilitation treatment of this population is not as well established as it is for patients with other neurological conditions. To assess functional outcome in brain tumour inpatients who underwent early rehabilitation after surgery. 75 patients who had undergone neurosurgery for primary BTs and 75 patients affected by stroke were enrolled in a case-control study. All patients were evaluated by means of a core set of clinical scales (Functional Independence Measure, Sitting Balance score, Standing Balance score, Hauser Index, Massachusetts General Hospital Functional Ambulation Classification). Patients were evaluated before the beginning (T0) and at the end (T1) of rehabilitation treatment. The neurorehabilitation programme consisted of individual 60-min sessions of treatment, administered once a day, six days a week, for four consecutive weeks. Speech therapy was included when aphasia was diagnosed. All the measures of outcome were indicative of substantial improvements for neuro-oncological and for stroke patients (P = 0.000). Analysis of subgroups showed that patients affected by meningioma achieved better results (in efficiency terms) as regards independence in activities of daily living (P = 0.02) and mobility (P = 0.04) compared with patients affected by glioblastoma or stroke. Rehabilitation after surgery can improve functional outcome, justifying the delivery of rehabilitation services, even during the acute phase, to BTs inpatients, irrespective of tumour type.

Caregiver burden and coping in early-stage Alzheimer disease.

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.

Memantine in Alzheimer's disease: experience in an Alzheimer's disease assessment unit.

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<0.01). CONCLUSIONS: Results confirmed the short-term effect of memantine, both in monotherapy and in combination with AchEIs in moderate-to-severe AD. This efficacy, albeit slight, was found to persist in the longer term.

Progression to dementia in a population with amnestic mild cognitive impairment: clinical variables associated with conversion.

The aim of this study was to investigate clinical predictors of, and rates of conversion to, dementia syndrome in a case series of patients with amnestic mild cognitive impairment (aMCI). Two hundred and eight aMCI subjects were followed over a six-year period. A lower Mini Mental State Examination score was a significant predictor of dementia, and mild cognitive impairment patients with behavioral and psychiatric symptoms showed a faster conversion rate.

Impact of healthcare-associated infections on functional outcome of severe acquired brain injury during inpatient rehabilitation.

To describe healthcare-associated infections in inpatient neuro-rehabilitation and their impact on functional outcome, a multicenter observational study with severe acquired brain injury (sABI) patients was performed. Patients were divided into infected (INF-group) or not infected (noINF-group) and assessed at admission and discharge, by means of the Glasgow Coma Scale (GCS), the Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), the Disability Rating Scale (DRS), and the modified Barthel Index (mBI). One hundred-nineteen patients were included in the INF-group, and 109 in the noINF-group. Culture specimens were found positive for bloodstream (43.8%), respiratory tract (25.7%), urinary tract (16.2%), gastro-intestinal system (8.6%) and skin (2.4%) infections. Multiple microorganisms were the most frequent (58.1%) and 55.5% of patients needed functional isolation due to multidrug resistant germs. The functional status of both groups improved after rehabilitation, but multivariable analyses showed that the INF-group showed a significantly lower gain to GCS (p = 0.008), DRS (p = 0.020) and mBI (p = 0.021) compared to the noINF-group. Length of stay (LOS) and number of skipped rehabilitative sessions were not statistically different between the groups; mortality rate was significantly higher in the INF-group (p = 0.04). Infected sABI patients showed longer LOS, significant increased mortality, and a lower functional outcome than not infected patients.

The effects of alcohol on cognition in the elderly: from protection to neurodegeneration.

The effects of chronic alcohol abuse on cognition are well known. Memory and executive functions appear to be the cognitive domains primarily impaired, and prefrontal and frontal damage is reported on neuroimaging studies both at micro- and macrostructural levels. Abstinence can partially reverse these alterations through mechanisms of neuroplasticity. Alcohol acts in a dose-dependent fashion, and a light-to-moderate consumption indeed has protective effects on cardiovascular risk factors and promotes anti-inflammatory and anti-oxidative processes. In the elderly on such a regimen, several epidemiological studies have reported a decreased risk of both coronary and cerebrovascular disease and of dementia. However, because of data heterogeneity and the presence of several confounding variables, further studies are needed to clarify these findings. In addition, the complexity of alcohol neurobiology (interaction of alcohol effects with genetic predisposition and environmental factors) and the occurrence of age-related changes should also be taken into account. As dementia, stroke and cardiovascular disease are the leading causes of mortality in older people in developed countries, a better knowledge of the mechanisms underlying the effects of alcohol intake may be helpful from the perspective not only of medical management but also of social health policy.

The Effect of Robotic Assisted Gait Training With Lokomat® on Balance Control After Stroke: Systematic Review and Meta-Analysis.

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 Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease. Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)-healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)-were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups. Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used. Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.