Kijpaisalratana Naruchorn, Phuah Chia-Ling, Ament Zsuzsanna, Bhave Varun M, Garcia-Guarniz Ana-Lucia, Duskin Jonathan, Couch Catharine A, Irvin M Ryan, Kimberly W Taylor
Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Departments of Neurology and Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA; Barrow Neuro Analytics Center, Barrow Neurological Institute, Phoenix, AZ, USA.
J Prev Alzheimers Dis. 2025 Apr;12(4):100086. doi: 10.1016/j.tjpad.2025.100086. Epub 2025 Feb 11.
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.
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.
Cross-sectional design.
Cohort of individuals who are clinically normal, mild cognitive impairment, or Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
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.
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.
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).
An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes.
肠道微生物群相关代谢产物与脑白质高信号（WMH）均与认知障碍独立相关。然而，尚不清楚肠道代谢产物与WMH是否相互作用影响痴呆。
研究肠道微生物代谢产物与认知结局之间的关联，并评估基线WMH的严重程度是否会影响肠道微生物代谢产物与认知结局之间的关联。
横断面设计。
阿尔茨海默病神经影像学倡议（ADNI）中临床正常、轻度认知障碍或阿尔茨海默病的个体队列。
共有578名参与者纳入分析，这些参与者有可用的基线3.0T二维液体衰减反转恢复（FLAIR）磁共振成像（MRI）扫描和基线肠道微生物代谢产物测量数据。
从FLAIR MRI获得肠道代谢产物测量值和自动WMH体积估计值，并用于评估与认知障碍的关联和相互作用。
在研究的104种代谢产物中，甘氨脱氧胆酸（GDCA）超过了错误发现率，并与阿尔茨海默病评估量表认知子量表第13版（ADAS-Cog13）评分相关（β = 0.12，95%可信区间 = 0.05 - 0.20，p = 0.001）以及由简易精神状态检查（MMSE）确定的认知障碍相关（比值比 = 2.11，95%可信区间 = 1.41 - 3.15，p < 0.001）。在WMH负担低的参与者中，GDCA与较高的ADAS-Cog13相关（β = 0.21，95%可信区间 = 0.10 - 0.32，p < 0.001），但在WMH负担高的参与者中则不然（β = 0.04，95%可信区间 = -0.07至0.14，p = 0.48；交互作用p = 0.02）。
GDCA水平升高与较差的认知相关。WMH严重程度改变了GDCA与认知结局之间的关联。
