Evidence map›Paper›PMID 28114437›Full record

ReviewJAMA neurology2017

Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.

Hussein N Yassine, Meredith N Braskie, Wendy J Mack, Katherine J Castor, Alfred N Fonteh, Lon S Schneider, Michael G Harrington, Helena C Chui

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in JAMA neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03613844 (The Delivery of Essential Fatty Acids to the Brain), which is not on this map. Cited by 92 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 3 pooled it
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03613844 phase2completednot on this mapstarted 2018, after this paper: background citation

The Delivery of Essential Fatty Acids to the Brain

TypeinterventionalSponsorUniversity of Southern CaliforniaRan2018 to 2024Enrolled365ConditionsBrain DHA Delivery and Alzheimer's Disease RiskArmsDHA, Placebo
3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Metabolomics and lipidomics study on serum metabolite signatures in Alzheimer's disease and mild cognitive impairment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  15. Review
  16. Nutrition: A non-negligible factor in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  17. Article
  18. Review
  19. Review
  20. Effects of APOE4 on omega-3 brain metabolism across the lifespan.Trends in endocrinology and metabolism: TEM · 2024
    Review

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Hussein N YassineDivision of Endocrinology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Meredith N BraskieImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey.
Wendy J MackDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Katherine J CastorDepartment of Neurosciences, Huntington Medical Research Institutes, Pasadena, California.
Alfred N FontehDepartment of Neurosciences, Huntington Medical Research Institutes, Pasadena, California.
Lon S SchneiderDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles6Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles.
Michael G HarringtonDepartment of Neurosciences, Huntington Medical Research Institutes, Pasadena, California.
Helena C ChuiDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles.
University of Southern California · USHuntington Medical Research Institutes · US

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KIM, PAUL E · 1985 to 2019
$41.0M
The delivery of essential fatty acids to the Brain in Alzheimer's diseaseR01AG054434 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2017 to 2021
$5.4M
Biomarkers of ABCA1 mediated functions in Alzheimers diseaseR01AG055770 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2017 to 2021
$4.2M
Growth factors, neuroinflammation, exercise, and brain integrityRF1AG041915 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2014
$2.9M
Alzheimer's disease risk analyzed using population imaging genomicsR01AG040060 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2011 to 2016
$2.5M
The Effect of Saturated Fat Ingestion on the HDL ProteomeK23HL107389 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2012 to 2016
$648k
NHLBI NIH HHS K23 HL107389NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG040060NIA NIH HHS R01 AG054434NIA NIH HHS R01 AG055770NIA NIH HHS RF1 AG041915
6 · The paper itself

Abstract

importanceThe apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA, APOE genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature. OBSERVATIONS: Although randomized clinical trials of ω-3 in symptomatic AD have had negative findings, several observational and clinical trials of ω-3 in the predementia stage of AD suggest that ω-3 supplementation may slow early memory decline in APOE4 carriers. Several mechanisms by which the APOE4 allele could alter the delivery of DHA to the brain may be amenable to DHA supplementation in predementia stages of AD. Evidence of accelerated DHA catabolism (eg, activation of phospholipases and oxidation pathways) could explain the lack of efficacy of ω-3 supplementation in AD dementia. The association of cognitive benefit with DHA supplementation in predementia but not AD dementia suggests that early ω-3 supplementation may reduce the risk for or delay the onset of AD symptoms in APOE4 carriers. Recent advances in brain imaging may help to identify the optimal timing for future DHA clinical trials. CONCLUSIONS AND RELEVANCE: High-dose DHA supplementation in APOE4 carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in APOE4 carriers is warranted.

Indexed as

Alzheimer DiseaseApolipoprotein E4Docosahexaenoic AcidsHumansApolipoprotein E4Docosahexaenoic Acids

Identifiers

PMID28114437
PMCPMC5812012
OpenAlexW2581962464

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.