Evidence map›Paper›PMID 42315445›Full record

Trial reportEBioMedicine2026

CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial.

Hussein N Yassine, Sara Ghasem Pour, Marlene Juarez, Isabella C Arrelanas, Nada Ali, Dante Dikeman, Ashley Sanchez, Jackson Park, Bilal Kerman, Marlon V Duro and 9 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2026. 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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 map

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

1 citing paper in PubMed.

  1. Article
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

19 authors.

Hussein N YassineDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: hyassine@usc.edu.
Sara Ghasem PourDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Marlene JuarezDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Isabella C ArrelanasDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nada AliDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Dante DikemanDepartment of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Ashley SanchezDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Jackson ParkDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Bilal KermanDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Marlon V DuroDepartment of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Isaac AsanteDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Institute for Technology and Medical Systems (ITEMS), Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Stan LouieDepartment of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Naoko KonoDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lina M D'OrazioDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Helena ChuiDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wendy J MackDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Michael G HarringtonDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Meredith N BraskieMark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lon S SchneiderDepartment of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Funding

USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8M
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
ApoE, ABCA1 and endosomal dysregulation in ADR01AG067063 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2020 to 2024
$3.4M
Brain cPLA2 as a mechanism for neuroinflammation in AD/ADRD with and without APOE4 Diversity SupplementRF1AG076124 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARVANITAKIS, ZOE, YASSINE, HUSSEIN N · 2022 to 2024
$2.5M
DHA brain delivery by APOE genotypeR21AG056518 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2018 to 2019
$464k
NIA NIH HHS P30 AG066530NIA NIH HHS R01 AG054434NIA NIH HHS R01 AG055770NIA NIH HHS R01 AG067063NIA NIH HHS R21 AG056518NIA NIH HHS RF1 AG076124
6 · The paper itself

Abstract

backgroundAPOE ε4 carriers have increased Alzheimer's disease risk and altered omega-3 metabolism. No large-scale prevention trials have tested high-dose docosahexaenoic acid (DHA) supplementation specifically in non-demented APOE ε4 carriers with low baseline omega-3 intake for early intervention.

methodsWe conducted a phase IIa 24-month, randomised, double-blind, placebo-controlled trial (NCT03613844) at the University of Southern California between September 2018 and May 2024. Participants aged 55-80 years without dementia, low dietary DHA intake (<200 mg/day), and ≥1 dementia risk factor were stratified by cerebrospinal fluid (CSF) collection willingness into lumbar puncture (LP) or no-LP arms. Within each arm, participants were randomised 1:1 to receive 2 g/day DHA or placebo, stratified by APOE ε4 status. Primary outcome was the 6-month CSF DHA-to-arachidonic acid (AA) ratio change. Secondary and exploratory outcomes included 24-month neuroimaging and cognitive measures.

findingsOf 739 screened individuals, 365 participants were randomised (181 LP arm, 184 no-LP arm). Mean age was 66.4 years (SD 5.7), 210 (58%) were female, 142 (39%) were Hispanic, 173 (47%) were APOE ε4 carriers. DHA supplementation increased CSF DHA/AA ratio at 6 months vs placebo (0.17 [95% CI 0.15-0.18] vs -0.02 [95% CI -0.04 to -0.0004]; difference 0.19 [95% CI 0.16-0.21]; p < 0.0001), independent of APOE ε4 status (interaction p = 0.71). Dropout was 38%, mainly due to COVID-19. No treatment differences were observed in brain volumes or cognitive performance over 24 months. Adverse events were comparable between groups, with no serious adverse events attributed to treatment.

interpretationHigh-dose DHA achieved CNS target engagement in non-demented older adults with low baseline omega-3 intake, independent of APOE ε4. Despite biochemical target engagement, no differences in cognition or brain structure were observed over 24 months. Future research should prioritise brain DHA metabolism over further supplementation trials.

fundingNational Institute on Aging (R01AG057684) and the ADDF (GC-201711-2014197).

Indexed as

Central Nervous SystemDementiaDietary SupplementsDocosahexaenoic AcidsAgedAged, 80 and overApolipoprotein E4Arachidonic AcidCognitionDouble-Blind MethodFemaleHumansMaleMiddle AgedApolipoprotein E4Arachidonic AcidDocosahexaenoic AcidsAlzheimer's diseaseAPOE ε4Brain healthCognitionDementia preventionDHA supplementationNeuroprotectionOmega-3 fatty acids

Identifiers

PMID42315445
PMCPMC13347776

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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.