Cognitive impact of multidomain intervention and omega 3 according to blood Aβ42/40 ratio: a subgroup analysis from the randomized MAPT trial.
Alzheimer’s disease
Amyloid blood biomarker
Clinical trial
Prevention
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
01
08
2023
accepted:
05
10
2023
medline:
27
10
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT01513252 .
Sections du résumé
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 .
Identifiants
pubmed: 37872582
doi: 10.1186/s13195-023-01325-3
pii: 10.1186/s13195-023-01325-3
pmc: PMC10594723
doi:
Substances chimiques
amyloid beta-protein (1-42)
0
Fatty Acids, Omega-3
0
Amyloid
0
Banques de données
ClinicalTrials.gov
['NCT01513252']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
183Subventions
Organisme : NIA NIH HHS
ID : R56 AG061900
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061900
Pays : United States
Investigateurs
Isabelle Carrié
(I)
Lauréane Brigitte
(L)
Catherine Faisant
(C)
Françoise Lala
(F)
Hélène Villars
(H)
Emeline Combrouze
(E)
Carole Badufle
(C)
Audrey Zueras
(A)
Christophe Morin
(C)
Gabor Abellan Van Kan
(GA)
Charlotte Dupuy
(C)
Yves Rolland
(Y)
Céline Caillaud
(C)
Pierre-Jean Ousset
(PJ)
Sherry Willis
(S)
Sylvie Belleville
(S)
Brigitte Gilbert
(B)
Francine Fontaine
(F)
Jean-François Dartigues
(JF)
Isabelle Marcet
(I)
Fleur Delva
(F)
Alexandra Foubert
(A)
Sandrine Cerda
(S)
None Marie-Noëlle-Cuffi
Corinne Costes
(C)
Olivier Rouaud
(O)
Patrick Manckoundia
(P)
Valérie Quipourt
(V)
Sophie Marilier
(S)
Evelyne Franon
(E)
Lawrence Bories
(L)
Marie-Laure Pader
(ML)
Marie-France Basset
(MF)
Bruno Lapoujade
(B)
Valérie Faure
(V)
Michael Li Yung Tong
(MLY)
Christine Malick-Loiseau
(C)
Evelyne Cazaban-Campistron
(E)
Françoise Desclaux
(F)
Colette Blatge
(C)
Thierry Dantoine
(T)
Cécile Laubarie-Mouret
(C)
Isabelle Saulnier
(I)
Jean-Pierre Clément
(JP)
Marie-Agnès Picat
(MA)
Laurence Bernard-Bourzeix
(L)
Stéphanie Willebois
(S)
Iléana Désormais
(I)
Noëlle Cardinaud
(N)
Marc Bonnefoy
(M)
Pierre Livet
(P)
Pascale Rebaudet
(P)
Claire Gédéon
(C)
Catherine Burdet
(C)
Flavien Terracol
(F)
Alain Pesce
(A)
Stéphanie Roth
(S)
Sylvie Chaillou
(S)
Sandrine Louchart
(S)
Kristel Sudres
(K)
Nicolas Lebrun
(N)
Nadège Barro-Belaygues
(N)
Jacques Touchon
(J)
Karim Bennys
(K)
Audrey Gabelle
(A)
Aurélia Romano
(A)
Lynda Touati
(L)
Cécilia Marelli
(C)
Cécile Pays
(C)
Philippe Robert
(P)
Franck Le Duff
(F)
Claire Gervais
(C)
Sébastien Gonfrier
(S)
Yannick Gasnier
(Y)
Serge Bordes
(S)
Danièle Begorre
(D)
Christian Carpuat
(C)
Khaled Khales
(K)
Jean-François Lefebvre
(JF)
Samira Misbah El Idrissi
(SM)
Pierre Skolil
(P)
Jean-Pierre Salles
(JP)
Nicola Coley
(N)
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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