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White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes
Naruchorn Kijpaisalratana1, Chia-Ling Phuah2, Zsuzsanna Ament3
1Center 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.
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.
Insights
Elevated glycodeoxycholic acid (GDCA) is linked to cognitive decline. White matter hyperintensities (WMH) severity influences this association, suggesting a complex interaction affecting dementia risk.
Area of Science:
- Neuroscience
- Gastroenterology
- Metabolomics
Background:
- Gut microbiome metabolites and white matter hyperintensities (WMH) are independently linked to cognitive impairment.
- The interaction between gut metabolites and WMH in influencing dementia remains unclear.
Purpose of the Study:
- To investigate the association between gut microbial metabolites and cognitive function.
- To determine if WMH severity modifies the relationship between gut metabolites and cognitive outcomes.
Main Methods:
- Cross-sectional study of 578 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
- Analysis included gut microbial metabolite measurements and WMH volume estimations from MRI scans.
- Cognitive outcomes were assessed using ADAS-Cog13 and MMSE.
Main Results:
- Glycodeoxycholic acid (GDCA) was significantly associated with worse cognitive performance (ADAS-Cog13 score and MMSE).
- GDCA showed a stronger association with cognitive decline in individuals with low WMH burden compared to those with high WMH burden.
- A significant interaction (p=0.02) was found between GDCA and WMH severity regarding cognitive outcomes.
Conclusions:
- Higher levels of GDCA correlate with poorer cognitive function.
- WMH severity plays a crucial role in modulating the impact of GDCA on cognitive health, highlighting a potential pathway in dementia development.
