Cognitive Intervention to Restore Capabilities for Learning and Retrieval of High-Fidelity Memory
Phase: NA
Conditions: Long-Term Memory Decline, Mild Cognitive Impairment
Sponsor: University of California, San Francisco

Wayfinding Intervention in High-Fidelity Long-Term 
Memory December 8, 2022
NCT 04253587 
Statistical Analysis Plan: 
Analyses were conducted under the intent-to-treat (ITT) 
principle, and data from all participants randomized to 
begin a training arm were included in the analyses. Each 
cognitive outcome measure is independent from the 
others (i.e., each measure uses a compartmentalized 
procedure, unique stimuli, and different metrics) and 
was considered as a potential measure of generalization 
of training effects in its own right. Therefore, the 
analyses of LDI scores and WALK scores were 
independent of each other. 
Mixed models ANOVA were employed to examine the 
differences across the two conditions (Trackers and 
Control) between T1 (baseline) and T2 (post-training). 
Data were analyzed and statistics calculated using IBM 
SPSS Statistics release 20.0, and the threshold of 
statistical significance for false positives was set at p < 
0.05. 

Research Protocol Summary 
Title: Wayfinding Intervention in High-Fidelity Long-Term Memory 
Rationale: Therapeutic interventions have not yet been shown to demonstrate 
restorative effects for declining long-term memory (LTM) that affects many healthy older 
adults. Our motivation was to demonstrate a cognitive intervention based on spatial 
wayfinding through unfamiliar surroundings that induced beneficial gains in untrained 
measures of high-fidelity LTM, which is the most precise form of LTM. 
Goals: Spatial navigation tasks have been applied to achieve environmental enrichment 
in animals, which refers to exposure and learning that have been linked to the vitality of 
the memory system in the brain. Labyrinth is a virtual reality (VR) spatial wayfinding 
game that mimics this environmental enrichment approach with the goal of improving, 
and potentially restoring, memory abilities in healthy older adults. The primary objective 
is to show training-induced gains in high-fidelity LTM (i.e., mnemonic discrimination). 
Design: All participants provided informed consent under UCSF IRB 19-27586. 
Experiments enrolled 49 healthy older adults (mean 69 years of age) per protocol in a 
randomized controlled type interventional study. Outcome data were assessed at 
baseline (T1) and post-training timepoints (T2), and the primary outcome measures 
assessed two capabilities for high-fidelity LTM retrieval. The two treatment arms were 
Labyrinth VR training versus placebo control narrative games played on an iPad tablet 
computer. After orientation to their respective treatment games, all participants 
completed an expectancy survey regarding how their treatment would affect cognitive 
performance. 
Methodology: Experiments used an HTC® VIVE™ VR system with the Unity cross-
platform game engine (©Unity Technologies) to present our spatial wayfinding game. 
The cognitive intervention required approximately 12 hours game play of either 
Labyrinth VR treatment, or four commercially available narrative computer games as 
placebo controls, over four weeks.  
    MDT was one primary outcome measure and provided an LDI score for each 
participant at each timepoint in order to assess generalization of Labyrinth training to 
untrained capability for mnemonic discrimination as a measure of high-fidelity LTM. 
Mixed design ANOVA (repeated factors for time T1|T2 X between factors for condition 
Labyrinth-VR | Controls) was used for the analysis of LDI. 
    WALK was another primary outcome measure and provided an Items Recalled score 
for each participant at each timepoint in order to assess generalization of Labyrinth 
training to untrained capability for recent autobiographical memory as a measure of 
high-fidelity LTM. Mixed design ANOVA (repeated factors for time T1|T2 X between 
factors for condition Labyrinth-VR | Controls) was used for the analysis of Items 
Recalled. 
 

Wayfinding Intervention in High-Fidelity Long-Term Memory
December 8, 2022
NCT 04253587
Statistical Analysis Plan:
Analyses were conducted under the intent-to-treat (ITT) principle, and 
data from all participants randomized to begin a training arm were 
included in the analyses. Each cognitive outcome measure is 
independent from the others (i.e., each measure uses a 
compartmentalized procedure, unique stimuli, and different metrics) and 
was considered as a potential measure of generalization of training 
effects in its own right. Therefore, the analyses of LDI scores and TOUR 
scores were independent of each other.
Mixed models ANOVA were employed to examine the differences 
across the two conditions (Trackers and Control) between T1 (baseline) 
and T2 (post-training). Data were analyzed and statistics calculated 
using IBM SPSS Statistics release 20.0, and the threshold of statistical 
significance for false positives was set at p < 0.05.
In consideration of a funding constraint, data were collected and 
analyzed only in the Experimental: LabyrinthVR Trackers and Placebo 
Comparator: Placebo Controls arms.