Education as Risk Factor of Mild Cognitive Impairment ‐ the Role of the Gut Microbiome.

Background: Research on social determinants of health has identified modifiable risk factors that contribute to an individual's risk of developing dementia [1]. Individuals with mild cognitive impairment (MCI) present a group with highest potential of lifestyle interventions due to the risk of progressing to dementia [2]. The pathways from identified modifiable risk factors for dementia such as education have not been clarified, however understanding the relationships between risk factors and MCI could help identify mechanisms for intervention and reducing risk of progressing to dementia. Previous findings found taxonomic differences in dementia and MCI patients, and further education linked to indicators of gut dysbiosis [3–5]. We sought to test the possibly mediating role of gut dysbiosis and taxonomic differences in the relationship between modifiable risk factors and MCI, independent of genetic risk for developing dementia. Method: Gut microbiome composition was ascertained with 16S rRNA gene amplicon sequencing. MCI classification was based on MoCA performance. Educational attainment in years was grouped. Mediation analysis [6] was conducted decomposing direct and indirect effects of educational attainment on MCI mediated by markers of dysbiosis (Chao1, Inverse Simpson, Shannon) while controlling for polygenic risk of Alzheimer's Disease, Lewy Body Dementia and Parkinson's Disease to account for different etiologic neurodegenerative pathways manifesting as MCI. Taxonomic differences across education groups were further tested (ANCOM‐BC, DESeq2) and PAM clustering based on relative abundance at Genus level was conducted to explore underlying signatures. Result: After exclusion of participants below age 50, or with missing data, n = 256 participants (n = 58 with MCI) of the Luxembourg Parkinson's Study without Parkinson's disease were eligible for analysis (M[SD] Age = 64.7[8.3] years). Higher vs lower educational attainment had a controlled direct effect (CDE) = 0.35 (P<.01) on MCI, Chao1 included as mediator. We did not find significant indirect effects via any indicator of dysbiosis. Clusters with lower abundance of Bacteroides relative to Prevotella and Ruminococcus were at higher risk of MCI. Conclusion: Our findings indicate direct effects of education not mediated by markers of dysbiosis. Taxonomic analysis suggests a signature linked to lower risk of dementia in higher educated individuals. [ABSTRACT FROM AUTHOR]