AbstractBackgroundAging‐related cognitive decline has been regarded as a normal consequence of aging. However, previous research on ‘SuperAgers’ suggests that such decline is not inevitable. The purpose of this study was to investigate the relationship between the microbiome and white matter integrity in SuperAgers, which may help us understand the mechanism that preserves memory function in these individuals.MethodWe enrolled a total of 115 elderly individuals aged 60 years or older with normal cognitive function, which was defined as scoring one standard deviation or more above the population norm on tests of memory, attention, language, visuospatial ability, and frontal function in the Seoul Neuropsychological Screening Battery. SuperAgers were defined based on their delayed recall scores compared to middle‐aged adults (45 years old) in both the Seoul Verbal Learning Test and the Rey‐Osterrieth Complex Figure Test. Diffusion tensor images were analyzed using tract‐based spatial statistics (TBSS). Parameters related to diffusion tensors were calculated at the voxel level to generate fractional anisotropy (FA) images using the DTIFit. FA values, a diffusion tensor parameter reflecting white matter fiber tract integrity, were measured and compared between SuperAgers and typical agers using the FSL randomise program. For microbiome analysis, EZ biocloud was used to perform alpha diversity, taxonomic hierarchy, and taxonomic composition analysis for each subject analysis. Group analysis was also conducted using the taxonomic composition values, and further group analysis was carried out using ACE, Chao1, and Jacknife, which are indicators of species richness. Statistical analyses were conducted using Statistical Package for Social Science 19.ResultCompared to typical agers, superagers showed a higher number of Firmicutes and Actinobacteria, which have been associated with higher cognitive function. However, there was no significant difference between superagers and typical agers. Additionally, an analysis of the association between p_firmicutes, c_mollicutes, o_lactobacilales and f_erysipelotrichaceae with white matter integrity showed no significant association.ConclusionBased on these results, it can be inferred that superagers may have a correlation with microbiome strains that are closely related to cognitive function, as well as white matter in the brain