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

Article type: Research Article

Authors: Saji, Naoki^{a; *} | Murotani, Kenta^b | Sato, Naoyuki^c | Tsuduki, Tsuyoshi^d | Hisada, Takayoshi^e | Shinohara, Mitsuru^c | Sugimoto, Taiki^{a; f} | Niida, Shumpei^g | Toba, Kenji^h | Sakurai, Takashi^{a; f; i}

Affiliations: [a] Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Aichi, Japan | [b] Biostatistics Center, Graduate School of Medicine, Kurume University, Fukuoka, Japan | [c] Department of Aging Neurobiology, Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan | [d] Laboratory of Food and Biomolecular Science, Department of Bioscience and Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan | [e] TechnoSuruga Laboratory Co., Ltd., Shizuoka, Japan | [f] Department of Prevention and Care Science, Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan | [g] Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan | [h] Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan | [i] Department of Cognition and Behavioral Science, Nagoya University Graduate School of Medicine, Aichi, Japan

Correspondence: [*] Correspondence to: Naoki Saji, MD, PhD, Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi 474-8511, Japan. Tel.: +81 562 46 2311; Fax: +81 562 48 2373; E-mail: sajink@nifty.com.

Abstract: 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.

Keywords: Biomarkers, cerebral small vessel disease, cognitive decline, dementia, gut microbiota

DOI: 10.3233/JAD-215141

Journal: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 1323-1335, 2022