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Aims: Continuity of care is an important issue in healthcare for persons after stroke. The present multi-center pilot study investigates the feasibility and efficiency of an innovative approach, the Human Empowerment Aging and Disability (HEAD), for digital-health motor and cognitive rehabilitation. The approach is explored within an in-clinic context (ClinicHEAD) and in continuity of care (HomeHEAD) for persons after chronic stroke. Methods: Thirty-four outpatients with chronic stroke (mean age 55 years, SD 13.7) participated. The HEAD VR protocol was administered in two consecutive phases: Phase I in clinic (ClinicHEAD) consisting of 4 weeks of 12 supervised HEAD rehabilitation sessions (45-min), including motor, cognitive and dual task for all participants; Phase II at home (HomeHEAD) consisted of 60 sessions of the same VR activities, 5 times/week for 3 months. All participants in the ClinicHEAD were allocated (ratio 1:2) to continue with tele-monitored home rehabilitation (HH, N = 11) or to follow usual care (UC, N = 23). Blind evaluation was carried out at baseline, after ClinicHEAD, after 3 months of HomeHEAD and at 3 months Follow-up. Primary outcomes were functional mobility [2-min Walking Test (2MWT)] and cognition [Montreal Cognitive Assessment (MoCA)]. Feasibility and acceptance were assessed with adherence to treatment and the System Usability Satisfaction. Within group analyses were done with dependent samples t -tests, and between groups HomeHEAD comparisons were carried out on change scores with independent samples t -test ( p = 0.05, two tailed). Results: The HEAD protocol was feasible with good adherence both in the ClinicHEAD phase (92%) and HomeHEAD (89%) phase, along with good perceived system satisfaction. ClinicHEAD resulted in a significant increase in functional mobility (2MWT, p = 0.02) and cognition (MoCA, p = 0.003) and most secondary outcome variables. At 3 months follow up of HomeHEAD the HH_group showed a further significantly greater maintenance of functional mobility with respect to UC_group ( p = 0.04). Conclusion: The HEAD VR protocol was feasible in clinical and at home tele-rehabilitation for persons in the chronic phase after stroke. In clinic the approach was effective in augmenting motor and cognitive abilities and at home it was effective in longterm maintenance of functional mobility, indicating its usefulness in continuity of care. Clinical Trial Registration: ClinicalTrials.gov, NCT03025126., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jonsdottir, Baglio, Gindri, Isernia, Castiglioni, Gramigna, Palumbo, Pagliari, Di Tella, Perini, Bowman, Salza and Molteni.)

Aims: We aimed to identify the significant predictors of ecological memory amelioration after the Human Empowerment Aging and Disability (HEAD) rehabilitation program, a multidimensional treatment for chronic neurological diseases. Materials and Methods: Ninety-three patients with Parkinson disease ( n = 29), multiple sclerosis ( n = 26), and stroke ( n = 38) underwent a multidimensional rehabilitation. We focused on changes after treatment on ecological memory (outcome measure) evaluated by Rivermead Behavioral Memory Test, Third Edition (RBMT-3). Minimal clinically important difference (MCID) after treatment were calculated for RBMT-3. The change score on RBMT-3 was categorized in positive effect, stabilization, or no effect of the treatment. Random forest classification identified who significantly benefited from treatment against who did not in terms of ecological memory functioning. Accordingly, logistic regression models were created to identify the best predictors of the treatment effect. A predicted probability value was derived, and the profile of the ideal candidate of HEAD protocol was shown by combining different ranks of significant predictors in a 3 × 3 matrix for each pair of predictors. Results: A significant number of cases reported positive effect of the treatment on ecological memory, with an amelioration over the MCID or a stabilization. The random forest analysis highlighted a discrete accuracy of prediction (>0.60) for all the variables considered at baseline for identifying participants who significantly benefited and who did not from the treatment. Significant logistic regression model (Wald method) showed a predictive role of Montreal Cognitive Assessment (MoCA; p = 0.007), 2 - Minute Walk Test (2MWT; p = 0.038), and RBMT-3 ( p < 0.001) at baseline on HEAD treatment effect. Finally, we observed a high probability of success in people with higher residual cognitive functioning (MoCA; odds ratio = 1.306) or functional mobility (2MWT; odds ratio = 1.013). Discussion: The HEAD program is a rehabilitation with effects on multiple domains, including ecological memory. Residual level of cognitive and/or motor functioning is a significant predictor of the treatment success. These findings confirm the intrinsic relationship subsisting between motor and cognitive functions and suggest the beneficial effects of physical activity on cognitive functions and vice versa ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Tella, Isernia, Pagliari, Jonsdottir, Castiglioni, Gindri, Gramigna, Canobbio, Salza, Molteni and Baglio.)

Parkinson's disease (PD) often leads to multifactorial motor and non-motor disabilities with resultant social restrictions. Continuity of care in this pathology, including a tailored home rehabilitation, is crucial to improve or maintain the quality of life for patients. The aim of this multicenter study was to test in a pilot sample of PD patients the efficiency and efficacy of the Human Empowerment Aging and Disability (HEAD) program. The virtual reality HEAD program was administered in two consecutive phases: (1) in clinic (ClinicHEAD, 12 45-minutes sessions, 3 sessions/week); (2) at home (HomeHEAD, 60 45-minutes sessions, 5 sessions/week). Thirty-one PD outpatients were enrolled [mean age (SD) = 66.84 (9.13)]. All patients performed ClinicHEAD, and after allocation (ratio 1:2) were assigned to the HomeHEAD or the Usual Care (UC) group. Motor, cognitive and behavioral outcome measures were assessed at enrollment (T0), at hospital discharge (T1), at 4 (T2) and 7 (T3) months after baseline. After ClinicHEAD (T1 vs. T0 comparison) a significant ( p < 0.05) improvement in functional mobility, balance, upper limb mobility, global cognitive function, memory, quality of life and psychological well-being was observed. After the HomeHEAD intervention there was an additional enhancement for upper limb mobility. At T3 follow-up, the UC group that did not continue the HEAD program at home showed a worsening with respect to the HomeHEAD group in balance and functional mobility. Furthermore, in the HomeHEAD group, a positive association was observed between adherence, mental and physical health (SF-12). A trend was also registered between adherence and positive affect. The digital health patient-tailored rehabilitation program resulted in improving motor and non-motor abilities and quality of life in clinical setting, enhancing the motor function in telerehabilitation at home, and maintaining the non-motor abilities and quality of life at follow-up. In the near future, people with PD can be supported also at home with individualized rehabilitation strategies for a better quality of life and wellbeing along with lower costs for society., (Copyright © 2020 Isernia, Di Tella, Pagliari, Jonsdottir, Castiglioni, Gindri, Salza, Gramigna, Palumbo, Molteni and Baglio.)

Although rehabilitation robotics seems to be a promising therapy in the rehabilitation of the upper limb in stroke patients, consensus is still lacking on its additive effects. Therefore, there is a need for determining the possible success of robotic interventions on selected patients, which in turn determine the necessity for new investigating instruments supporting the treatment decision-making process and customization. The objective of the work presented in this preliminary study was to verify that fully robot assistance would not affect the physiological oscillatory cortical activity related to a functional movement in healthy subjects. Further, the clinical results following the robotic treatment of a chronic stroke patient, who positively reacted to the robotic intervention, were analyzed and discussed. First results show that there is no difference in EEG activation pattern between assisted and no-assisted movement in healthy subjects. Even more importantly, the patient's pretreatment EEG activation pattern in no-assisted movement was completely altered, while it recovered to a quasi-physiological one in robot-assisted movement. The functional improvement following treatment was large. Using pretreatment EEG recording during robot-assisted movement might be a valid approach to assess the potential ability of the patient for recovering.

The "glucocorticoid cascade hypothesis" for pathological ageing of the brain is supported by strong experimental data, but the clinical correlates are far less clear. The basal ACTH and cortisol secretion have been studied before and after the dexamethasone suppression test in patients in the early stages of clinically probable Alzheimer's disease and in controls, and the results were all normal. These findings do not support the hypothesis that the pathological brain ageing of Alzheimer's type is caused by hyperactivity of the pituitary-adrenal axis.

The response of plasma beta-endorphin (beta-EP) to dexamethasone suppression was studied in 14 patients with Alzheimer's disease (AD), 14 patients with Parkinson's disease (PD), and 13 age-matched controls in order to evaluate whether an impairment of the opiate system is present in these neurodegenerative disorders. Basal circulating beta-EP was in normal range in all subjects, although the mean concentration was slightly reduced in the patients compared to controls. After 1 mg dexamethasone given at 11:00 p.m. the night before, plasma beta-EP concentration measured at 08:00 a.m. and 04:00 p.m. was not inhibited in AD and PD patients while it was significantly reduced in controls. Circulating ACTH and cortisol were similar in patients and controls and a normal inhibition of plasma cortisol after dexamethasone was observed in 13/14 AD and 12/14 PD patients. The resistance of beta-EP to dexamethasone inhibition is consistent with previous clinical and experimental data indicating a disorder of the opiate system in brain degenerative diseases.