Oxidized products of omega-6 and omega-3 long chain fatty acids are associated with increased white matter hyperintensity and poorer executive function performance in a cohort of cognitively normal hypertensive older adults

Lynne Shinto, David Lahna, Charles F. Murchison, Hiroko Dodge, Kirsten Hagen, Jason David, Jeffrey Kaye, Joseph F. Quinn, Rachel Wall, Lisa C. Silbert, Michelle Mielke

Research output: Contribution to journalArticle

Abstract

Background: Cerebrovascular disease is a common cause of dementia in older adults, and potentially preventable with early intervention. Oxylipins are produced from the oxidation of long-chain polyunsaturated fatty acids (PUFA) possessing potent vascular effects. Oxylipins generated from the cytochrome P450 pathway are enzymatically converted to diols by soluble epoxide hydrolase (sEH); sEH products have been associated with small vessel ischemic disease. Little is known about oxylipins' impact on markers of dementia risk. Objective: An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition. Methods: Thirty-seven non-demented participants with controlled hypertension (mean age 65.6 years) were enrolled in a dementia prevention study investigating fish oil and lipoic acid on preserving cognitive function. Baseline associations between plasma oxylipins, white matter hyperintensity (WMH), and Trails-B were examined using linear regression. P450-derived diol/epoxide ratio was an indirect measure of sEH activity. Results: Omega-6 derived 9-HODE was associated with increased WMH (p = 0.017) and reduced grey matter volume (p = 0.02). Omega-6 P450-derived diol/epoxide ratio 9,10-DiHOME/9,10-EpOME was associated with increased WMH (p = 0.035) and poorer performance on Trails-B (p = 0.05); ratio14,15-DHET/14,15-EET was associated with increased WMH (p = 0.045). Omega-3 P450-derived diol/epoxide ratio 19,20-DiHDPE/19,20-EpDPE was associated with increased WMH (p = 0.04) and poorer performance on Trails-B (p = 0.04). Arachidonic acid was associated with better performance on Trails-B (p = 0.012); Omega-3 derived 16,17-EpDPE was associated with decreased WMH (p = 0.005). Conclusions: With the exception of arachidonic acid, it was specific oxylipin products, not their parent PUFAs, that were associated with unfavorable and favorable MRI and cognitive markers of dementia risk.

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
JournalJournal of Alzheimer's Disease
Volume74
Issue number1
DOIs
StatePublished - 2020

Keywords

  • Alzheimer's disease
  • cross-sectional studies
  • fatty acids
  • humans
  • oxylipins
  • vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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