Relationship between Plasma Neurofilament Light Chain, Gut Microbiota, and Dementia: A Cross-Sectional Study

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial. Objective: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function. Methods: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses. Results: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75-48.2, p < 0.001). Conclusion: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study.