White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes

作者：Naruchorn Kijpaisalratana, Chia‐Ling Phuah, Zsuzsanna Ament, Varun Bhave, Ana‐Lucia Garcia Guarniz, Jonathan Duskin, Catharine A. Couch, Marguerite R. Irvin, W. Taylor Kimberly · 发表于：The Journal of Prevention of Alzheimer s Disease · 年份：2025 · DOI：10.1016/j.tjpad.2025.100086 · 被引用次数：6 · 研究领域：Gut microbiota and health、Metabolomics and Mass Spectrometry Studies、Diet and metabolism studies

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 p...