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Cynthia M Carlsson1,2,3,4, Hannah Zylstra4,5, Kate Cronin4,5

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Summary
This summary is machine-generated.

High-dose icosapent ethyl (IPE) did not improve cerebrospinal fluid biomarkers of vascular or metabolic health in US military Veterans at risk for Alzheimer's disease. Further research is needed to clarify the role of omega-3 fatty acids in modifying AD risk.

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Area of Science:

  • Neurology
  • Cardiovascular Health
  • Biomarker Discovery

Background:

  • US military Veterans are susceptible to Alzheimer's disease (AD) dementia, potentially due to vascular factors.
  • Omega-3 fatty acids, like eicosapentaenoic acid (EPA), have anti-inflammatory and anti-atherogenic properties and may reduce dementia risk.
  • The effect of high-dose EPA icosapent ethyl (IPE) on cerebrospinal fluid (CSF) markers of vascular and metabolic health in AD-at-risk adults is unknown.

Purpose of the Study:

  • To investigate the effect of 18-month high-dose IPE treatment on CSF biomarkers of vascular and metabolic health in cognitively unimpaired Veterans at risk for AD.
  • To explore changes in CSF markers related to endothelial function, inflammation, and oxidation using NULISAseq technology.

Main Methods:

  • The Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid Study (BRAVE-EPA) was an 18-month, placebo-controlled, double-blind randomized trial involving 131 Veterans.
  • Participants received 4g daily of IPE or placebo, with CSF collection, MRI, and cognitive testing at baseline, 9, and 18 months.
  • CSF samples were analyzed using NULISAseq CNS disease panel to measure VEGF family proteins, reflecting vascular and metabolic health markers.

Main Results:

  • Eighty-six participants had available CSF for analysis at baseline and 18 months.
  • IPE treatment did not significantly alter CSF biomarkers of vascular or metabolic health compared to placebo.
  • No changes were observed in CSF pTau-217, a marker of AD pathology.

Conclusions:

  • In this cohort of cognitively unimpaired Veterans, 18 months of IPE did not impact CSF biomarkers of vascular/metabolic health or AD pathology.
  • While EPA shows potential in managing inflammatory and atherogenic processes, further studies are required to determine IPE's role in AD risk modification via vascular pathways.