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
Affiliations: [a] Department of Neurology, Oregon Health and Science University, Portland, OR, USA
| [b] Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA
| [c] Department of Neurology, Veterans Affairs Medical Center, Portland, OR, USA
Correspondence:
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Correspondence to: Lynne Shinto, ND, MPH, Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, CR120, Portland, OR 97239, USA. Tel.: +1 503 494 5035; Fax: +1 503 346 8156; E-mail: shintol@ohsu.edu.
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.
