Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Oct 23;15(1):183.
doi: 10.1186/s13195-023-01325-3.

Cognitive impact of multidomain intervention and omega 3 according to blood Aβ42/40 ratio: a subgroup analysis from the randomized MAPT trial

Julien Delrieu  1 , Bruno Vellas  2 , Sophie Guyonnet  2 , Christelle Cantet  2 , Vitaliy Ovod  3 , Yan Li  3 , James Bollinger  3 , Randall Bateman  3   4 , Sandrine Andrieu  5 ; MAPT/DSA group
Collaborators, Affiliations
Randomized Controlled Trial

Cognitive impact of multidomain intervention and omega 3 according to blood Aβ42/40 ratio: a subgroup analysis from the randomized MAPT trial

Julien Delrieu et al. Alzheimers Res Ther. .

Abstract

Background: In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings.

Methods: MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects according to amyloid blood status at 12, 36, and 60 months. In this subgroup analysis (n = 483), amyloid status was defined by plasma Aβ42/40 ratio (cutoff ≤ 0.0107). The primary outcome measure was the change in cognitive composite score after a 1, 3, and 5-year clinical follow-up.

Results: The intention-to-treat (ITT) population included 483 subjects (161 positive and 322 negative amyloid participants based on plasma Aβ42/40 ratio). In the positive amyloid ITT population, we showed a positive effect of MI plus omega 3 on the change in composite cognitive score in 12 (raw p = .0350, 0.01917, 95% CI = [0.0136 to 0.3699]) and 36 months (raw p = .0357, 0.2818, 95% CI = [0.0190 to 0.5446]). After correction of multiple comparisons and adjustments, these differences were not significant (adjusted p = .1144 and .0690). In the per-protocol positive amyloid group (n = 154), we observed a significant difference between the combined intervention and placebo groups at 12 (p = .0313, 0.2424, 0.0571 to 0.4276) and 36 months (p = .0195, 0.3747, 0.1055 to 0.6439) persisting after adjustment. In the ITT and per-protocol analyses, no cognitive effect was observed in the positive and negative amyloid group at 60-month visit.

Conclusions: These findings suggest a benefit of MI plus omega 3 in positive blood amyloid subjects. This promising trend needs to be confirmed before using blood biomarkers for screening in preventive trials.

Trial registration: ClinicalTrials.gov Identifier: NCT01513252 .

Keywords: Alzheimer’s disease; Amyloid blood biomarker; Clinical trial; Prevention.

PubMed Disclaimer

Conflict of interest statement

JD has received payment/honoraria from Biogen (presentation for Biogen in 2021); and has participated on a Data Safety Monitoring Board or Advisory Board for French board for Roche in 2020–2022. SA has received grants from Europe, Ipsen, and France Alzheimer’s, served as a consultant for Ipsen, Pierre Fabre, Lilly, Nestlé, Sanofi, and Servier, and received non-financial support from Biogen, Nutrition Santé, Pfizer, and Icon, and other forms of support from the AMPA Association. BV receives grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regeneron, Sanofi, Roche, AstraZeneca, LPG Systems, Nestlé, and Alzheon, and personal fees from Lilly, Lundbeck, MSD, Otsuka, Roche, Sanofi, Biogen, Nestlé, Transition Therapeutics, and Takeda. Washington University and Randall Bateman have equity ownership interest in C2N Diagnostics and receive income based on technology (blood plasma assay) licensed by Washington University to C2N Diagnostics. RJB receives income from C2N Diagnostics for serving on the scientific advisory board. Washington University, with RJB as co-inventor, has submitted the US nonprovisional patent application “Plasma Based Methods for Determining A-Beta Amyloidosis.” RJB has received honoraria as a speaker/consultant/advisory board member from Amgen, AC Immune, Eisai, Hoffman-LaRoche, and Janssen; and reimbursement of travel expenses from AC Immune, Hoffman-La Roche and Janssen. All the other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Place of the amyloid plasma analysis in relation to MAPT and ancillary studies. MAPT multidomain Alzheimer’s preventive trial
Fig. 2
Fig. 2
Trial profile for the amyloid blood MAPT study. MAPT multidomain Alzheimer’s preventive trial, MI multidomain intervention
Fig. 3
Fig. 3
Mean change from baseline in composite cognitive score over 60 months (intention-to-treat population, n = 483). MI multidomain intervention, Amyloid+ positive amyloid status, Amyloid − negative amyloid status
See this image and copyright information in PMC

References

    1. Vellas B, Carrie I, Gillette-Guyonnet S, Touchon J, Dantoine T, Dartigues JF, et al. MAPT study: a multidomain approach for preventing Alzheimer’s disease: design and baseline data. J Prev Alzheimers Dis. 2014;1(1):13–22. - PMC - PubMed
    1. Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 2017;16(5):377–389. doi: 10.1016/S1474-4422(17)30040-6. - DOI - PubMed
    1. Solomon A, Turunen H, Ngandu T, Peltonen M, Levälahti E, Helisalmi S, et al. Effect of the apolipoprotein E genotype on cognitive change during a multidomain lifestyle intervention: a subgroup analysis of a randomized clinical trial. JAMA Neurol. 2018;75(4):462–470. doi: 10.1001/jamaneurol.2017.4365. - DOI - PMC - PubMed
    1. Delrieu J, Payoux P, Carrié I, Cantet C, Weiner M, Vellas B, et al. Multidomain intervention and/or omega-3 in nondemented elderly subjects according to amyloid status. Alzheimers Dement. 2019;15(11):1392–1401. doi: 10.1016/j.jalz.2019.07.008. - DOI - PubMed
    1. Blennow K, Zetterberg H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J Intern Med. 2018;284(6):643–663. doi: 10.1111/joim.12816. - DOI - PubMed

Publication types

Associated data