The Impact of A Multi-Domain Intervention on Cerebral Glucose Metabolism: Analysis from the Randomized Ancillary FDG PET MAPT trial

Abstract

Background: The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism.

Methods: MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented, and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to « MI group » or « No MI group ». The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months and 12 months, and cerebral Magnetic Resonance Imaging scans at baseline The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis.

Results: The intention-to-treat population included 67 subjects (34 in the « MI group » and 33 in the « No MI group ». No significant MI effect was observed on primary outcome at 6 and 12 months. In the exploratory voxel-wise analysis, we observed a difference in favor of « MI group » on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months.

Conclusions: MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression.

Trial registration: ClinicalTrials.gov Identifier, NCT01513252.