Randomized trial of marine n-3 polyunsaturated fatty acids for the prevention of cerebral small vessel disease and inflammation in aging (PUFA trial): Rationale, design and baseline results

Gene Bowman, Lisa Silbert, Hiroko Dodge, David Lahna, Kirsten Hagen, Charles F. Murchison, Diane Howieson, Jeffrey Kaye, Joseph Quinn, Lynne Shinto

Research output: Contribution to journalArticle

Abstract

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

Original languageEnglish (US)
Article number735
JournalNutrients
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Cerebral Small Vessel Diseases
Omega-3 Fatty Acids
omega-3 fatty acids
polyunsaturated fatty acids
inflammation
Inflammation
biomarkers
placebos
Biomarkers
apolipoprotein E
dementia
Apolipoprotein E4
endpoints
magnetic resonance imaging
blood vessels
soybean oil
Placebo Effect
Soybean Oil
White Matter
risk factors

Keywords

  • Cognitive decline
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • Elderly
  • Executive function
  • MRI
  • Neuroimaging
  • Vascular cognitive impairment
  • White matter hyperintensities

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

@article{bf31fa2bf32a466ba2813e4c22266c60,
title = "Randomized trial of marine n-3 polyunsaturated fatty acids for the prevention of cerebral small vessel disease and inflammation in aging (PUFA trial): Rationale, design and baseline results",
abstract = "Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61{\%} were female, 28{\%} were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.",
keywords = "Cognitive decline, Docosahexaenoic acid, Eicosapentaenoic acid, Elderly, Executive function, MRI, Neuroimaging, Vascular cognitive impairment, White matter hyperintensities",
author = "Gene Bowman and Lisa Silbert and Hiroko Dodge and David Lahna and Kirsten Hagen and Murchison, {Charles F.} and Diane Howieson and Jeffrey Kaye and Joseph Quinn and Lynne Shinto",
year = "2019",
month = "4",
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doi = "10.3390/nu11040735",
language = "English (US)",
volume = "11",
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T1 - Randomized trial of marine n-3 polyunsaturated fatty acids for the prevention of cerebral small vessel disease and inflammation in aging (PUFA trial)

T2 - Rationale, design and baseline results

AU - Bowman, Gene

AU - Silbert, Lisa

AU - Dodge, Hiroko

AU - Lahna, David

AU - Hagen, Kirsten

AU - Murchison, Charles F.

AU - Howieson, Diane

AU - Kaye, Jeffrey

AU - Quinn, Joseph

AU - Shinto, Lynne

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

AB - Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

KW - Cognitive decline

KW - Docosahexaenoic acid

KW - Eicosapentaenoic acid

KW - Elderly

KW - Executive function

KW - MRI

KW - Neuroimaging

KW - Vascular cognitive impairment

KW - White matter hyperintensities

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DO - 10.3390/nu11040735

M3 - Article

VL - 11

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JF - Nutrients

SN - 2072-6643

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