DHA Brain Delivery Trial

Conditions

Brain DHA Delivery and Alzheimer's Disease Risk

Keywords

Alzheimer's disease, Docosahexaenoic Acids, Apolipoprotein E4

Brief summary

Carrying the APOE ɛ4 allele is the strongest genetic risk factor for developing Alzheimer's disease. The goal of this project is to identify whether carrying the APOE ɛ4 allele is associated with reduced delivery of DHA to the brain. This information will help us identify the target population that could benefit from DHA supplementation to prevent cognitive decline.

Detailed description

The Brain DHA Delivery Trial will examine the effect of APOE genotype on the changes of cerebrospinal fluid (CSF) DHA to Arachidonic acid (AA) ratio in 184 cognitively healthy older individuals in response to DHA supplementation. Randomized clinical trials have yielded mixed results on the effect DHA supplementation on cognitive outcomes. This study asks the critical question of whether DHA gets into the brain in sufficient amounts after supplementation, and whether APOE genotype affects brain penetrance. This trial will also test the effect of DHA supplementation on changes in brain structural and functional connectivity assessed by MRI, and changes in cognition after two years of supplementation in all 368 participants.

Yassine HN, Pour SG, Juarez M, Arrelanas IC, Ali N, Dikeman D, Sanchez A, Park J, Kerman B, Duro MV, Asante I, Louie S, Kono N, D'Orazio LM, Chui H, Mack WJ, Harrington MG, Braskie MN, Schneider LS.

2026-06-18

10.1016/j.ebiom.2026.106316

Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia

Hussein N. Yassine, Isabella C. Arellanes, A. Mazmanian, Luis de la Cruz‐Merino, José Antônio Baddini Martínez et al. (19 authors)

The Journal of Prevention of Alzheimer s Disease2023-06-0710 citations

10.14283/jpad.2023.77

Entorhinal thickness: A marker of DHA supplementation efficacy?

Hussein N. Yassine, Victoria Solomon, Xulei He, Isabella Cordova, Naoko Kono et al. (11 authors)

Alzheimer s & Dementia2021-12-01

10.1002/alz.055680

Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.

Arellanes IC, Choe N, Solomon V, He X, Kavin B, Martinez AE, Kono N, Buennagel DP, Hazra N, Kim G, D'Orazio LM, McCleary C, Sagare A, Zlokovic BV, Hodis HN, Mack WJ, Chui HC, Harrington MG, Braskie MN, Schneider LS, Yassine HN.

2020-07-1794 citations

10.1016/j.ebiom.2020.102883

Interventions

DRUGDHA

DHA supplementation

DRUGPlacebo

Placebo for DHA

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

double blind and randomized placebo controlled

Eligibility

Sex/Gender

ALL

Age

55 Years to 80 Years

Healthy volunteers

Yes

Inclusion criteria

* Age: ≥ 55 and ≤ 80 * At least one dementia risk factor (obesity, education years, hypertension, hyperlipidemia) * Mini-Mental State Examination (MMSE) ≥ 25 * Logical Memory II delayed recall score ≥ 6 and ≤ 18 .

Exclusion criteria

* Diagnosis of dementia as assessed by the investigator * Use of omega-3 preparations in the last 3 months * \> 200 mg/day of DHA consumption using a validated questionnaire * Use of donepezil, rivastigmine, galantamine and/or memantine * Alcohol or drug abuse * A concomitant serious disease such as active cancer treatment or HIV. * Participation in a clinical trial in the last 30 days * Use of anticoagulants such as Plavix or Coumadin or the newer generation blood thinners.

Design outcomes

Primary

Measure	Time frame	Description
change in cerebrospinal fluid fatty acid levels after the intervention in 184 subjects	6 months	cerebrospinal fluid fatty acids assessed by mass spectrometry

Other

Measure	Time frame	Description
Change in functional connectivity using resting state functional MRI in all 368 participants	2 years	Functional Connectivity
Change in structural connectivity using MRI in all 368 participants	2 years	Structural connectivity
Change in cognitive measures using the Neuropsychological Outcomes (RBANS) in all 368 participants	2 years	RBANS battery

Countries

United States

Outcome results

None listed