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Updated: Jul 3, 2026
Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging
Published on: November 8, 2012
Resolving cognitive heterogeneity in white matter hyperintensities through integrated analyses of microbiome,
Xiaotao Xu1,2,3, Xia Zhou4, Mengwei Zhang1,2,3
1Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Introduction:
Individuals with similar white matter hyperintensities (WMH) burden show heterogeneous cognitive outcomes, yet the biological mechanisms underlying this variability remain incompletely understood.
Methods:
We integrated 16S rDNA sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging (MRI) to comprehensively characterize gut microbiome, plasma metabolome, and brain glymphatic function in 56 healthy controls, 40 WMH with normal cognition (WMH-NC), and 49 WMH with cognitive impairment (WMH-CI).
Results:
Group comparisons revealed differences in six bacterial genera, three plasma metabolites, and five glymphatic markers across three groups, with Acetivibrio, 1,5-naphthalenediamine, beta-uridine, free water fraction within the white matter, and index of diffusivity along the perivascular spaces (ALPS index) showing differences between WMH-CI and WMH-NC. Correlation and mediation analyses demonstrated associations between microbiota and cognition, mediated by tetradecyldiethanolamine and ALPS index.
Discussion:
These findings provide preliminary insights into plausible microbiota-metabolites-glymphatic function-cognition associations in WMH, potentially informing more targeted interventions for vascular cognitive impairment.
