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Voxel-based assessments of treatment effects on longitudinal brain changes in the Multidomain Alzheimer Preventive Trial cohort

Abstract : Objective: The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the effect of omega-3 supplementation and a multidomain intervention (physical activity, cognitive training and nutritional advice) on cognitive decline of people with subjective memory complaint. In term of cognitive testing, no significant effect on cognitive decline was found over the 3-year follow-up. Yet, in the context of dementia-related conditions, brain morphological changes can be used to foretell the cognitive evolution. In this paper, we evaluate the effect of the interventions on the evolution of the brain morphology using the MR images acquired during MAPT. Methods: Subjects in the MAPT cohort with two MRI acquisitions, at baseline and at 36 months, were included , resulting in a subset of 376 subjects distributed in the 4 intervention groups: multidomain intervention plus omega-3, multidomain intervention plus placebo, omega-3 alone, and placebo alone. The morphological changes were assessed from volume measurements of regions of interest and a voxel-wise deformation-based approach. The primary outcome is the longitudinal deformation observed between the baseline image and the 3-year follow-up. Results: The multi-domain intervention is associated with a significant effect on the 3-year morphological evolution. The effect is similar within the two groups undergoing the intervention regardless of the omega-3 or placebo treatment. The voxel-wise deformation-based approach shows that the differences are mainly located in the left peri-ventricular area next to the temporoparietal junction (TPJ). These morphological changes correspond to a slower morphological evolution and are correlated with a better performance in cognitive assessments. These results could not be observed using the volumetric morphometry approach. No effect of omega-3 was observed. Discussion: In this study, we found that the multidomain intervention has a significant effect on morphological changes that are usually associated with the cognitive decline. This result suggests that effects at the level of cognitive decline may be visible in the long term, and that the cognitive scores may not be powerful enough to detect changes after 3 years. We argue that the use of neuroimaging could help define whether early intervention strategies are effective to delay cognitive decline and dementia.
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https://hal.inria.fr/hal-02166357
Contributor : Raphael Sivera <>
Submitted on : Tuesday, November 19, 2019 - 1:37:44 PM
Last modification on : Saturday, June 20, 2020 - 2:45:14 PM

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Raphaël Sivera, Nicolas Capet, Valeria Manera, Roxane Fabre, Marco Lorenzi, et al.. Voxel-based assessments of treatment effects on longitudinal brain changes in the Multidomain Alzheimer Preventive Trial cohort. Neurobiology of Aging, Elsevier, 2020, 94, pp.50-59. ⟨10.1016/j.neurobiolaging.2019.11.020⟩. ⟨hal-02166357v2⟩

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