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Grant Abstract: Omega 3 pufas for the vascular component of age-related cognitive decline

Grant Number: 5R01AG043398-03
PI Name: Shinto
Project Title: Omega 3 pufas for the vascular component of age-related cognitive decline

Abstract: The main objective of the study entitled “Omega-3 PUFAs for the vascular component of age-related decline” is to determine if omega 3 polyunsaturated fatty acids, administered as fish oil capsules, can slow the accumulation of brain MRI derived white matter hyperintensities (WMH) over 3 years in a population at risk for dementia by advanced age, evidence of both baseline WMH burden and low plasma levels of eicosapentaenoic and docosapentaenoic acid (EPA and DHA). This pilot trial is designed to collect preliminary data on omega-3 pufa effects on total WMH progression, plasma biomarkers of endothelial function and rate of cognitive change over time. The study is a randomized, double-blind, placebo-controlled trial. Nondemented elders age 80 and older with WMH burden and lower plasma EPA and DHA will be enrolled. One hundred and fifty subjects will be randomized, half to fish oil supplementation, and half to placebo oil over a 3 year term. Aim 1 will assess the effects of this therapy on WMH progression. Our hypothesis is that those randomized to omega-3 pufas will appreciate less WMH progression. Aim 2 will assess the pufa effects on biomarkers of endothelial function as a potential modulator of the effects on total WMH and cognitive change. We hypothesize that omega-3 pufas will improve biomarkers of endothelial function that include: soluble adhesion molecules and inflammatory products (sICAM-1, sVCAM-1, E-Selectin, TNF?, IL-6, hsCRP), and beta amyloid metabolites (abeta 40 and 42). Aim 3 will collect preliminary data on the change in executive function and processing skills to inform the more definitive prevention trials in the future. We hypothesize that pufas slow vascular pathology mediated cognitive aging. Expanding Aim 2 to include the measurement of polyunsaturated fatty acid metabolites offers a novel and innovative approach to better understand the mechanism of action of omega-3 fatty acids for the vascular component of age-related decline. Because little is known about how omega-3 fatty acid, generated through diet or dietary supplementation, act to modify vascular tone, the proposed study offers a novel and innovative approach to better understand the mechanism of action of omega-3 fatty acids and their relationship to other blood and brain biomarkers of vascular function.

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