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

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.