Mri changes following treatment of Glp-1 analogue, liraglutide in Alzheimer's disease

Abstract

Background: Preclinical evidence in transgenic models of Alzheimer's disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate AD conducted at 24 centres in the UK. Method(s): As a part of this study, a total of 204 Alzheimer's participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects underwent volumetric MRI scans at baseline and during follow up. Volumetric changes from baseline to follow up in MRI scans were evaluated using both regional volume analysis and voxel based morphometric analysis Result: MRI analysis demonstrated that temporal lobe volume, total grey matter volume and frontoparietal volume change was lower in liraglutide treated patients compared to the placebo group. Voxel based morphometry (VBM) analysis demonstrated that liraglutide-treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo. Conclusion(s): In the ELAD study, participants with mild to moderate AD who received liraglutide had slower reduction in MRI volume and cognition compared to the placebo demonstrating a potential benefit of liraglutide in the treatment of Alzheimer's disease. These findings highlight the potential of GLP-1 analogues in the treatment of Alzheimer's disease.