Exploring to Remediate Behavioral Disturbances of Spatial Cognition

Study Overview
=================
Brief Summary
-----------------
Spatial navigation (SN) has been reported to be one of the first cognitive domains to be affected in Alzheimer's disease (AD), which occurs as a result of progressive neuropathology involving specific brain areas. Moreover, the epsilon 4 isoform of Apolipoprotein-E (APOE-ε4) has been associated with both sporadic and familial late-onset AD and patients with Mild Cognitive Impairment (MCI) due to AD are more likely to progressively deteriorate. It will be investigated (i) whether amyloid-positive MCI patients and APOE-ε4 carriers show subtle changes of SN prior to the overt symptoms of AD disorientation, both in virtual and in naturalistic open-space tasks, and (ii) the effect of a combined treatment of computer-based and virtual reality tasks in those presenting such an impairment. Finally, (iii) threshold algorithms based on physiological parameters and gait analysis will be set up to support senior citizens at increased risk in maintaining their ability to independently navigate urban environments. Different types of navigational guidance will be examined on a sample of 76 older adults by the AppleGame, and the Detour Navigation Test-modified version. It is expected that patients with MCI due to AD and APOE-ε4 carriers show reduced SN performances than individuals with subjective cognitive impairment and healthy controls in the experimental tasks, with potential improvements after cognitive rehabilitation. Altered SN performances of individuals at increased risk to develop AD may inform future advanced technological applications in providing valuable information on threshold algorithms based on physiological parameters and gait analysis during elders' traveling to unfamiliar locations.

Official Title
-----------------
Exploring to Remediate Behavioral Disturbances of Spatial Cognition in Community-dwelling Senior Citizens With Mild Cognitive Impairment by Innovative Technological Apparatus.

Conditions
-----------------
Spatial Navigation

Intervention / Treatment
-----------------
* Behavioral: Virtual and computer-based cognitive remediation training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age over 65 years; education not less than 5 years; basic ICT skills measured by the Catholic University devoted software Exclusion Criteria: presence of visual, hearing or motor impairment significantly interfering with spatial navigation tasks; neurological/psychiatric disease or other medical conditions preventing spatial navigation; history of alcohol or drugs addiction; intake of psychotropic drugs; presence of dementia.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy controls<br>Elderly people without cognitive impairment or subjective cognitive decline. | |
| Subjective cognitive decline<br>Individuals presenting cognitive complains that are not confirmed by neuropsychological testing. | |
| patients with MCI due to AD<br>Patients with Mild Cognitive Impairment with abnormal spinal fluid test for amyloid beta protein. | Behavioral: Virtual and computer-based cognitive remediation training<br>* Amyloid-positive MCI patients, and individuals carrying the ApoE- ε4 allele will undergo a combined intervention of computer-based sessions of a spatial memory task by the Erica software (Giunti, Florence, Italy) and VR navigation sessions by the NeuroVirtual 3D software (Serino et al., 2010), in order to improve spatial memory for landmarks location and mental frame syncing for supporting spatial scenarios, respectively. The intervention will last one month for a total of 12 sessions (3 days a week, 50 minutes per session).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detecting drop errors (DEs) and composite disorientation score (CDS) in individuals at increased risk to develop AD in virtual and naturalistic spatial navigation tasks, respectively | Lower performances in virtual navigation tasks (higher DEs) and in naturalistic navigation (CDS>1) in patients with MCI due to AD and in APOE-e4 carriers than healthy controls and individuals with subjective cognitive decline | March-November 2023 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improving spatial memory after a combined cognitive training (virtual reality and computer-based cognitive remediation) in a subgroup of patients with MCI due to AD and APOE-e4 carriers | Higher performances in the Corsi learning Suvra-span test | December 2023-January 2024 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
elderly, spatial navigation, Alzheimer's disease, mild cognitive impairment, subjective cognitive decline, APOE, assistive technology