Clinical trial NCT05944601: Exploring to Remediate Behavioral Disturbances of Spatial Cognition
Official title: Exploring to Remediate Behavioral Disturbances of Spatial Cognition in Community-dwelling Senior Citizens With Mild Cognitive Impairment by Innovative Technological Apparatus.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Spatial Navigation
Keywords: spatial navigation
Alzheimer's disease
mild cognitive impairment
subjective cognitive decline
elderly
APOE
assistive technology
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
First posted: 2023-07-13
Enrollment: 83
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Alzheimer's disease (AD) is characterized by a progressive deterioration of cognitive functions with episodic memory loss and spatial disorientation (SD) as main features. Getting lost in community due to AD is associated with a wide range of negative consequences, such as a strong decrease in patients' quality of life. Episodes of SD in the elderly can increase the possibility of being recovered in a nursing home, caused by a loss of the sense of autonomy as well as an increase in potential injuries and, in the worst cases, even death. Additionally, caregiver burden and increased stress, as well as scarce community resources represent other significant problems related to patients' SD. New technological solutions, such as virtual reality (VR), represent promising means for AD assessment and intervention, especially when they can reveal poor ecological performances. In addition to the advanced age, the ε4 allele of Apolipoprotein-E (APO-E) represents the most important risk factor for AD, providing the opportunity to evaluate subclinical behavioral alterations in individuals with subjective cognitive decline (SCD), and Mild Cognitive Impairment (MCI) due to AD, which represents the prodromic phase of dementia. Deterioration of spatial navigation (SN) abilities is often present early in the course of AD. Therefore, a better understanding the neural mechanisms related to SN impairment in patients at high risk of developing AD can help timely diagnosis and intervention. The present study, adopting a technological apparatus for the detection and the rehabilitation of SN deficits, aims to: (i) investigate the performances obtained on SN tasks in a sample of community-dwelling older adults grouped into three levels (healthy controls, individuals with SCD and patients with MCI due to AD), undergoing virtual (The AppeGame) and naturalistic open-space tests (Detour Navigation Test-modified version); (ii) correct SN deficits by computer-based cognitive remediation sessions and VR sessions; (iii) educate participants at high risk of developing dementia about the opportunity offered by technology in supporting SN in exploring urban circuits.

We will analyze results of the virtual and ecological tasks of SN as a function of age, ApoE genotype and belonging of one the three groups, using a multiple linear regression model. The subgroups of participants at highest risk of developing AD will be administered the aforementioned combined cognitive rehabilitation sessions, with a test/retest analysis. Finally, through an online technological monitoring system, participants will be provided personalized feedbacks via smartphone digital health applications connected to a wearable equipped with sensors, in order to self-manage during their journeys alone in urban environments thanks to the use of threshold algorithms capable of supporting their SN.

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.

Primary outcomes:
measure: 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
timeFrame: March-November 2023
Secondary outcomes:
measure: 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
timeFrame: December 2023-January 2024
Other outcomes:
measure: To educate a dyad (subject and caregiver) about the usefulness of a portable assistive technology for spatial navigation in community settings
timeFrame: January 2023-February 2024
Locations:
city: Milano
country: Italy
facility: Istituto Auxologico Italiano
state: Lombardy
Study officials:
References: