Neural and Clinical Correlates of Rehabilitation in Neurodegenerative Conditions

Currently, the impact of drug therapies on neurodegenerative conditions is very limited; The drugs available are mostly symptomatic and recent drug trials with new molecules have given contrasting results about the possibility of slowing down progression of disease. Therefore, clinically there is a strong interest in possible non-pharmacological intervention strategies for preserving functionality and limiting progression of disease as far as possible, reducing disability, and improving quality of life for both patients and their caregivers. Neurodegenerative diseases, such as Alzheimer's disease (AD) and, in some cases Parkinson's disease (PD), are characterized by a progressive cognitive decline. During the initial and mild cognitive impairment (MCI) phase, subjects report subjective disorders and show an objective and measurable cognitive impairment, although they maintain independence in day-to-day life activities. No consensus has been reached on the effect of non-pharmacological approaches to contrast cognitive decline, but there is a general agreement that these approaches are more likely to succeed the sooner they are implemented and the more accurately they act on the domains involved in the cognitive decline process.

The current longitudinal and multicenter study aims to apply innovative cognitive telerehabilitation (TR) approaches to the MCI population, to assess the impact of the different cognitive telerehabilitation approaches on brain network connectivity, acquired by means of high-density electroencephalogram (HD-EEG) and functional magnetic resonance imaging at rest (rs-fMRI). Moreover, the protocol will evaluate the effects of cognitive TR on neuropsychological measures. The primary outcome will be evaluated by means of a direct comparison between brain network connectivity measures before and after the intervention and by means of a comparison with a control group of MCI subjects, who will be involved in unstructured cognitive activities.

Condition Condition: Early stages of cognitive impairment due to neurodegenerative diseases, i.e. AD and PD.

Telerehabilitation Approaches Network-based Cognitive Training (NBCT) - A cognitive training specifically designed to promote the co-activation of multiple brain areas (i.e., central nodes), modulating the functional connectivity of specific resting state networks (RSNs) (i.e., Default Mode Network, DMN, e Salience Network, SN). This rehabilitation package has been used in face-to-face mode on a sample of healthy subjects (average age: 66 years), in whom a rehabilitation-induced "up-regulation" effect of the functional connectivity of the rear central nodes of the DMN was observed. Subsequently, this training approach has been tested in MCI-AD, MCI-PD and in patients with relapsing-remitting multiple sclerosis who complained of mild cognitive deficits. Within the framework of this study, the rehabilitation program will be implemented on a telerehabilitation platform (i.e. Khymeia) and will be administered through a virtual connection. A link will be provided for each rehabilitation session, which will allow participants to access and use the rehabilitation protocol through a web browser on their personal computer, tablet or mobile. This approach offers many advantages in terms of practicality, ease of use and accessibility for study participants.

Home-based Cognitive Rehabilitation (HomeCoRe) system - software for cognitive rehabilitation specially developed for the initial stages of deterioration (amnestic MCI, MCI-PD, mild AD), the usability and effectiveness of both in the person version (CoRe), as well as in remote rehabilitation (HomeCore) in the short and long term has been verified in the hospital field also in combination with neurostimulation techniques. HomeCoRe is an adaptive patient-tailored treatment that returns a Weighted score of performance for each exercise and each session to monitor patient's progress even remotely and adjust the level of difficulty of the proposed exercises accordingly. The mentioned strategy is applied to avoid over or under stimulation of the patient. The software provides an easy to access platform through which the patient interacts via a touch screen. The usability and acceptance of the home version of HomeCoRe has already been tested in a small group of patients in the early stages of cognitive impairment.