journal articles
WHITE MATTER HYPERINTENSITY SEVERITY MODIFIES GUT METABOLITE ASSOCIATION WITH COGNITIVE OUTCOMES
Naruchorn Kijpaisalratana, Chia-Ling Phuah, Zsuzsanna Ament, Varun M. Bhave, Ana-Lucia Garcia-Guarniz, Jonathan Duskin, Catharine A. Couch, M. Ryan Irvin, W. Taylor Kimberly, Alzheimer\'s Disease Neuroimaging Initiative, Alzheimer Disease Metabolomics Consortium
BACKGROUND: Gut microbiome-associated metabolites and white matter hyperintensities (WMH) are independently associated with cognitive impairment. However, it is unclear if gut metabolites and WMH interact to influence dementia.
OBJECTIVES: To examine the association between gut microbial metabolites and cognitive outcomes and assess whether the severity of baseline WMH would impact associations between gut microbial metabolites and cognitive outcomes.
DESIGN: Cross-sectional design. Setting: Cohort of individuals who are clinically normal, mild cognitive impairment, or Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants: A total of 578 participants with available baseline 3.0T 2D-Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) scans and baseline gut microbial metabolite measurement were included in the analysis.
MEASUREMENTS: Gut metabolite measurements and automated WMH volume estimations were obtained from FLAIR MRI and were used to assess the association and interaction with cognitive impairment.
RESULTS: Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05–0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41–3.15, p < 0.001). GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10–0.32, p < 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02).
CONCLUSION: An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes.
CITATION:
Naruchorn Kijpaisalratana ; Chia-Ling Phuah ; Zsuzsanna Ament ; Varun M. Bhave ; Ana-Lucia Garcia-Guarniz ; Jonathan Duskin ; Catharine A. Couch ; M. Ryan Irvin ; W. Taylor Kimberly ; Alzheimer's Disease Neuroimaging Initiative ; Alzheimer Disease Metabolomics Consortium (2025): White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100086