Clinical trial NCT04253587: Wayfinding Intervention in High-Fidelity Long-Term Memory
Official title: Cognitive Intervention to Restore Capabilities for Learning and Retrieval of High-Fidelity Memory
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Long-Term Memory Decline
Mild Cognitive Impairment
Keywords: amnestic MCI without dementia
cognitive training
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2020-02-05
Enrollment: 50
Sex: ALL
Minimum age (years): 62
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 (LTM)). Interventions capable of sustaining improved learning and flexible association of new information into LTM remain elusive. Interventions have yet to be developed 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 development of a cognitive training intervention that targets sustained improvement in capabilities for 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.

The significance of this platform is from the effects in brain and behavior arising from cognitive training, which can generalize to improvements in untrained capability for high-fidelity LTM. Research in rodents and 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 Labyrinth spatial wayfinding game was developed in-house to incorporate full scientific rigor, as with procedures in any properly controlled behavioral experiment. The game uses 3D and 2.5D computer graphics tools, as well as numerous levels of adaptive challenge, to deliver a dynamic, engaging experience for participants throughout the training regimen. Training can be administered with and without participant ambulation in movement through wayfinding runs.

A participant's pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen, including collection of functional MRI (fMRI) and structural MRI data. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval.

The a priori hypothesis is that effectiveness of the wayfinding game intervention would be evidenced by post-training improvements in retrieval of high-fidelity LTM and associated 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 45-minute, brisk 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 and post-assessment immediately after training regimen is completed
measure: WALK Change in Recall
timeFrame: baseline immediately before and post-assessment immediately after training regimen is completed
measure: Changes in Volumetric-based Brain Morphometry Associated With Training-induced Changes in Mnemonic Discrimination
timeFrame: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
measure: Changes in Task-based Cortical Functional Connectivity Associated With Training-induced Changes in Mnemonic Discrimination
timeFrame: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
Secondary outcomes:
measure: Remote Cognitive Module (RCM)
timeFrame: baseline immediately before and post-assessment immediately after training regimen is completed
measure: Test of Visual Attention Change in Top-down Control
timeFrame: baseline immediately before and post-assessment immediately after training regimen is completed
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:
citation: Wais PE, Arioli M, Anguera-Singla R, Gazzaley A. Virtual reality video game improves high-fidelity memory in older adults. Sci Rep. 2021 Jan 28;11(1):2552. doi: 10.1038/s41598-021-82109-3.