The prevalence of neurodegenerative diseases is expected to increase over the next years, in parallel with the aging of the world population. Therefore, it is important to identify new methods to prevent, delay or stop the neurodegenerative waterfall responsible for dementia conversion. To date, there is no fully proven pharmacological treatment for cognitive impairment and the available pharmacological treatments have limited efficacy because consist in symptomatic drugs with adverse side effects. On this point, non-pharmacological intervention may represent adjunctive therapy to medications in order to prevent or delay the onset of the cognitive deficits or dementia. Recently we evaluated the effectiveness of a computerized cognitive training (CoRe) in patients with early cognitive impairment. The main goal of the present protocol is to evaluate the efficacy of the home-based version of CoRe (Home CoRe). To this end, mild dementia or early cognitive impairment, and persons with Subjective Cognitive Impairment (SCI) are enrolled and randomly assigned to the experimental group (Home CoRe) or control group (CoRe). All patients are evaluated before (T0) and after (T1) treatment with an exhaustive neuropsychological assessment. Furthermore, follow-up visits are scheduled 6 months (T2) and 12 months (T3) after the end of the treatment.

Non-pharmacological intervention may represent adjunctive therapy to medications in order to delay the onset of the cognitive deficits or dementia. Moreover, increasing evidence suggests that environmental and lifestyle factors (education, cognitive engagement, experience..) impact on cognitive functions and brain plasticity during the lifetime and also during aging. These modifiable factors moderate differences in cognitive aging and are protective for the development of dementia.

Among non-pharmacological approaches, previous studies observed a positive effect of Cognitive Training (CT) both in healthy elderly people and patients in the early stage of neurodegenerative diseases. Moreover, the advances in the development of Information & Communication Technologies (ICT) has prompted the possibility to develop computer-based solution for the training of cognitive functions, being able to overcome traditional-training advantages. However, some issue remain unresolved and larger randomized controlled trials are necessary to examine long-term CT effects, due to the lack of longitudinal studies. Our previous data demonstrated that CT program with CoRe software is safe and effective on cognition in patient with Parkinson Disease-Mild Cognitive Impairment, in the attempt of briefly stabilizing cognitive decline, delaying the downward trajectory. The same pattern of findings resulted when using CoRe in patients with Mild Cognitive Impairment (MCI) and mild Alzheimer's Disease (AD). Among ICT advantages there is the fact that they offer the possibility to develop patient tailored interventions that can be easily delivered not only in-person but also remotely at patients' homes. It means that they could simplify the therapist's work in terms of the planning, design, and management of the cognitive intervention also outside from the clinical setting. However, some concerns have slowed the integration of home-based interventions into clinical practice, such as the fact that people with advanced age or cognitive deficit might have poor computer skills and difficulties managing technological devices on their own. Thus, the overall efficacy of home-based CT programs is still under debate.

In this frame, the primary goal of this single-blind randomized controlled trial is to assess whether a home-based CT (Home CoRe) could offer comparable effects (non-inferiority trial) to those of an in-person CT (CoRe). A secondary goal is to follow these effects with respect to the evolution of cognitive decline. These two interventions are evaluated also in terms of treatment adherence.

Both treatment protocols consist of 18 sessions (3 session/week, 45 minutes/day) of CT with CoRe vs HomeCoRe software (training memory and logical-executive functions).

Patients with mild dementia, early cognitive impairment (i.e., MCI and vascular cognitive impairment (VCI)), and SCI are recruited from Neuropsychology/Alzheimer's Disease Assessment Unit and Neurorehabilitation Unit of IRCCS Mondino Foundation. Patients' diagnosis is formulated on the basis of a comprehensive neuropsychological evaluation (baseline cognitive assessment - T0) according to the guidelines presented in the literature. The following standardized tests assessing different domains are used:

• global cognitive function: Mini-Mental State Examination (MMSE) and Montreal Montreal Overall Cognitive Assessment (MoCA);
• memory: verbal (Verbal Span; Digit Span) and spatial (Corsi's blocktapping test - CBTT) span; verbal long-term memory (Logical Memory Test immediate and delayed recall; Rey's 15-word test immediate and delayed recall); spatial long-term memory (Rey Complex Figure delayed recall - RCF-dr);
• logical-executive functions: non-verbal reasoning (Raven's Matrices 1947 - RM47); frontal functionality (Frontal Assessment Battery - FAB); semantic fluency (animals, fruits, car brands), phonological fluency (FAS);
• attention: visual selective attention (Attentive Matrices); simple speed processing and complex attention (Trail Making Test parts A - TMT A and part B - TMT B);
• visuospatial abilities: constructive apraxia Rey Complex Figure copy - RCF-copy.

The same battery is also used at follow-up visits; parallel versions are applied when available (verbal long-term memory tests), in order to avoid the learning effect. All the test scores are corrected for age, sex, and education and compared with the values available for the Italian population.

At the baseline, the cognitive reserve is assessed using Cognitive Reserve Index questionnaire (CRIq). The patients' functional status is assessed using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) at the baseline and at the last follow-up visit after one year (T3). Moreover, mood is assessed using the Beck Depression Inventory (BDI) at the baseline and at the follow-up visits (T1, T2 and T3), while quality of life were assessed using the 36-Item Short Form Health Survey questionnaire (SF-36) at the baseline and at the follow-up visits six months (T2) and one year (T3) after training. Subjective evaluation of intervention success is also considered by means of the Patient Global Impression of Change (PGIC) and the Patients Reported Outcome Measures (PROMS), administered at T0 and T1. Treatment adherence is evaluated considering the number of CT sessions carried out.

All the patients recruited undergo baseline cognitive assessment (T0). Patients who met the inclusion and exclusion criteria are enrolled and randomly assigned to the experimental group (Home CoRe) or control group (CoRe).

Inclusion Criteria:

• presence of mild dementia, mild cognitive impairment; vascular cognitive impairment, subjective cognitive impairment;
• age between 50 and 85 years;
• educational level ≥ 5 years.

Exclusion Criteria:

• MMSE < 20
• CRD > 1
• pre-existing cognitive impairment (e.g. aphasia, neglect);
• severe disturbances in consciousness;
• concomitant severe psychiatric disease or others neurological conditions (e.g. depression and behavioral disorders).

Single (neuropsychologist for cognitive assessments)