Cognitive Intervention Effects Vary as a Function of Plasma Neurofilament Light Chain Levels: A PICMOR Randomized Controlled Trial

Abstract

Background: There is a difference in the neuronal state of individuals. However, this has not been taken into consideration in most intervention studies. Recent advances in analytical technologies in hematological examination enabled us to evaluate neuronal states in a relatively convenient manner. Objective: Using these advanced technologies, we aimed to investigate whether cognitive intervention effects vary as a function of levels of blood-based biomarkers, such as neurofilament light chain (NfL), since plasma NfL could be a biomarker of neurodegenerative diseases including Alzheimer's disease. Methods: In this study, we employed a group conversation-based intervention methodology named Photo-Integrated Conversation Moderated by Robots (PICMOR), which has been shown to improve verbal fluency in older adults. To examine the possibility of varying effects of this intervention method according to the neuronal state of each individual, we conducted a randomized controlled trial (UMIN Clinical Trials Registry number: UMIN000036599) and investigated how longitudinal changes in cognitive performance, such as verbal fluency, vary with the NfL level measured at the baseline. Results: As the main result, positive intervention effects of PICMOR on verbal fluency were observed in individuals with lower level of NfL, which indicate a relatively intact neuronal state, whereas negative intervention effects were identified in individuals with higher NfL level. Conclusion: Our findings suggest that cognitive intervention effects vary depending on level of Nfl in the plasma. Thus, future intervention studies should take into account the neuronal status of the participants to examine intervention effects.

Home-Based Cognitive Intervention for Healthy Older Adults Through Asking Robots Questions: Randomized Controlled Trial

“…This study has some strengths. One strength is that we presented a technical framework for examining the impact of “asking questions,” an important factor for conversation-based interventions for cognitive function, which was lacking in our previous studies [ 17 21 ]…”

“…Another strength of this study is that we successfully conducted home-based interventions while most intervention studies, including our previous ones [ 17 21 ], have been conducted on-site. Notably, this study demonstrated that home-based interventions are feasible even though some participants were unfamiliar with digital devices.…”

“…For instance, resting-state functional connectivity between the left inferior frontal gyrus, one of the most important brain regions for verbal fluency, and the right temporal pole, a semantic-related brain region, positively correlated with enhanced verbal fluency performance [ 18 ]. Moreover, we conducted another RCT using PICMOR and examined whether the intervention effects on verbal fluency varied as a function of neuronal states estimated from blood-based biomarkers, such as plasma neurofilament light chain [ 21 ]. The results showed that individuals with lower neurofilament light chain, indicating a relatively intact neuronal state, performed better in a category fluency task.…”

Web-Based Group Conversational Intervention on Cognitive Function and Comprehensive Functional Status Among Japanese Older Adults: Protocol for a 6-Month Randomized Controlled Trial

“…The main outcome measure is cognitive function. Specifically, we hypothesized that the PICMOA may stimulate linguistic and executive functions through fundamental conversation activities based on the results of previous RCTs [22,23,27] and mechanistic hypothesis based on the explanatory investigation using multimodal MRI [24][25][26]. Thus, we will specifically focus on verbal fluency as the primary outcome, which may reflect linguistic and executive functions.…”

“…Based on the above evidence, we hypothesized that social communication-based interventions would be effective in maintaining cognitive function. Consequently, a series of our previous RCTs examined the effect of structural face-to-face group conversation intervention and consistently observed some positive effects on verbal fluency [22,23]. Our explanatory investigation using multimodal magnetic resonance imaging (MRI) identified the brain network, brain regions, and brain structure that could benefit from the intervention.…”