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",
day = "1",
doi = "10.3390/nu11040735",
language = "English (US)",
volume = "11",
journal = "Nutrients",
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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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U2 - 10.3390/nu11040735

DO - 10.3390/nu11040735

M3 - Article

VL - 11

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JF - Nutrients

SN - 2072-6643

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