White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes - 27/03/25

Doi : 10.1016/j.tjpad.2025.100086

Naruchorn Kijpaisalratana ^a,^b,^c,^d, Chia-Ling Phuah ^e,^f, Zsuzsanna Ament ^a,^d, Varun M. Bhave ^g, Ana-Lucia Garcia-Guarniz ^d, Jonathan Duskin ^d, Catharine A. Couch ^h, M. Ryan Irvin ^h, W. Taylor Kimberly ^a,^d,^g,^⁎
for the
Alzheimer's Disease Neuroimaging Initiative^¹
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: ADNI_Acknowledgement_List.pdf.
and the
Alzheimer Disease Metabolomics Consortium^²
Data used in preparation of this article were generated by the Alzheimer's Disease Metabolomics Consortium (ADMC). As such, the investigators within the ADMC provided data but did not participate in analysis or writing of this report. A complete listing of ADMC investigators can be found at: team/.
^a Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
^b Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
^c Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
^d Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
^e Departments of Neurology and Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA
^f Barrow Neuro Analytics Center, Barrow Neurological Institute, Phoenix, AZ, USA
^g Harvard Medical School, Boston, MA, USA
^h Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA

^⁎Corresponding author at: 55 Fruit Street, Lunder 644, Boston, MA 02114 USA.55 Fruit Street, Lunder 644BostonMA02114USA

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Abstract

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.

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Keywords : Gut metabolite, White matter hyperintensity, Cognitive impairment, Dementia

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Introduction

Methods

Study design and population

Cognitive assessment

Image processing for global and region of interest (roi)-based white matter hyperintensities

Amyloid burden parameters

Metabolite measurements

Statistical analyses

Results

Study population and baseline characteristics

Gut microbial metabolites and cognitive outcomes

White matter hyperintensity as an effect modifier of the gut microbial metabolites

White matter hyperintensity spatial patterns modify gdca association with cognition

Discussion

Conclusions

Fundings

Ethics approval and consent to participate

Esportazione

Vol 12 - N° 4

Articolo 100086- aprile 2025 Ritorno al numero

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White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes - 27/03/25

Abstract

Background

Objectives

Design

Measurements

Results

Conclusion

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