4.7 Article

Circulating metabolites are associated with brain atrophy and white matter hyperintensities

Journal

ALZHEIMERS & DEMENTIA
Volume 17, Issue 2, Pages 205-214

Publisher

WILEY
DOI: 10.1002/alz.12180

Keywords

Alzheimer's disease; cholesterol; glucose; lipids; magnetic resonance imaging (MRI); metabolism

Funding

  1. BBMRI-NL
  2. Dutch government (NWO) [184.021.007, 184033111]
  3. European Union's Horizon 2020 research and innovation program as part of the Common mechanisms and pathways in Stroke and Alzheimer's disease (CoSTREAM) project [667375]
  4. European Union Innovative Medicine Initiative (IMI) program, Alzheimer Disease Apolipoprotein Pathology for Treatment Elucidation and Development (ADAPTED) [115975]
  5. European Union's Horizon 2020 research and innovation program Marie Sklodowska-Curie Research and Innovation Staff Exchange (RISE) [645740]
  6. Stichting Alzheimer Nederland
  7. Stichting VUmc fonds
  8. Stichting Dioraphte
  9. NWO-FCB [057-14-004]
  10. NIHR biomedical research center at UCLH
  11. European Commission
  12. Dutch Research Council (ZonMW)
  13. Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation
  14. Weston Brain Institute
  15. Alzheimer Netherlands
  16. Stichting Equilibrio
  17. ZonMW Memorabel grant [733050814]

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The study found that high glucose levels were associated with brain atrophy and WMH, while levels of small HDL particles were linked to brain atrophy. The research suggests that circulating metabolites may help in the development of future intervention trials.
Introduction: Our aim was to study whether systemic metabolites are associated with magnetic resonance imaging (MRI) measures of brain and hippocampal atrophy and white matter hyperintensities (WMH). Methods: We studied associations of 143 plasma-based metabolites with MRI measures of brain and hippocampal atrophy and WMH in three independent cohorts (n = 3962). We meta-analyzed the results of linear regression analyses to determine the association of metabolites with MRI measures. Results: Higher glucose levels and lower levels of three small high density lipoprotein (HDL) particles were associated with brain atrophy. Higher glucose levels were associated with WMH. Discussion: Glucose levels were associated with brain atrophy and WMH, and small HDL particle levels were associated with brain atrophy. Circulating metabolites may aid in developing future intervention trials.

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