Clinical trial NCT05625425: Wayfinding Intervention and Long-Term Memory
Official title: Virtual Reality Interventions to Stimulate Capabilities for Learning and Retrieval of High-Fidelity Memory
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Long-Term Memory Decline
Mild Cognitive Impairment
Keywords: amnestic MCI without dementia
cognitive training
cognitive aging
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2022-11-23
Enrollment: 200
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits.

Detailed description: A hallmark of higher cognition is the capability for flexible association of diverse bits of information stored in memory, such that experiences can be remembered in detailed and distinct terms (i.e., high-fidelity long-term memory). Interventions capable of sustaining improved learning and flexible association of new information into long-term memory (LTM) have shown promising pilot results, and further development is expected to find treatments to attenuate the decline of high-fidelity LTM in normal aging or provide therapeutic treatment for patients with cognitive impairment without dementia (i.e., MCI).

This project applies a translational neuroscience approach in further development of a cognitive training intervention that targets sustained improvement in capabilities for long-term memory (LTM) and cognitive control. Treatments use commercially available head-mounted display Virtual Reality (VR) technology and tablet computers to present a deeply immersive spatial wayfinding video game.

Based on preliminary results, the hypothesis is that immersion in a game to navigate errands through unfamiliar, visually complex neighborhoods (i.e., wayfinding) will be an effective means to environmental enrichment, which refers to a process whereby new and complex experiences bring change to brain and behavior. Research in humans shows that learning a new, enriched environment spurs the healthy function of the hippocampus and supports lifelong neurogenesis. Adult-borne hippocampal neurogenesis has been linked as the neurobiological basis for the formation of new, high-fidelity memories.

The significance of this project includes functionality for remote training procedures (i.e., at home). The availability for participants to complete some of the experiment procedures at home will expand enrollment opportunities and prove the practicality of the intervention outside of a clinical setting.

The Labyrinth spatial wayfinding game uses 3D and 2.5D computer graphics tools to present dozens of levels of adaptive challenge and deliver a dynamic, engaging experience for participants throughout the training regimen. In this project, participants will effect game movement using hand controllers while playing the game in a seated position.

For each participant, pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval and control of sustained visual attention, and some measures will include collection of associated functional MRI (fMRI) and structural MRI data.

Effectiveness of the wayfinding game intervention will be evidenced by post-training improvements in retrieval of high-fidelity LTM and cognitive control capabilities. FMRI results associated with the measured cognitive improvements will localize changes in functional brain networks that support gains in memory capabilities. Structural MRI measures will assess morphometric and volumetric changes from pre- to post-training assessments.

Eligibility criteria: Inclusion Criteria:

* fluent speakers of English
* completed 12 or more years of education
* normal or corrected-to-normal vision
* dexterity to comfortably operate the scanner-compatible response box
* freedom from physical and neurological conditions contra-indicated for fMRI
* must confirm physical stamina and comfort for semi-weekly brisk 30-minute walks on level ground

Exclusion Criteria:

* use of psychotropic medications
* history of concussions or dizziness, vestibular or balance problems
* significant discomfort with virtual reality experiences

Primary outcomes:
measure: MDT change in mnemonic discrimination
timeFrame: baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2) providing for a composite score T2-T1
measure: TOUR change in recall
timeFrame: baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2) providing for a composite score T2-T1
measure: Volumetric-based brain morphometry for gray and white matter
timeFrame: collected in association with Outcome 1, at baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2)
measure: Task-based cortical functional connectivity associated with mnemonic discrimination capability and in control of sustained visual attention
timeFrame: collected in association with Outcome 1, at baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2)
Secondary outcomes:
measure: Remote Cognitive Module (RCM)
timeFrame: baseline immediately before training regimen begins
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Mission Bay
state: California
Study officials:
affiliation: Neuroscape, Department of Neurology
name: Peter E Wais, PhD
role: PRINCIPAL_INVESTIGATOR
References: