AUTHOR=Gejl Michael , Gjedde Albert , Egefjord Lærke , Møller Arne , Hansen Søren B. , Vang Kim , Rodell Anders , Brændgaard Hans , Gottrup Hanne , Schacht Anna , Møller Niels , Brock Birgitte , Rungby Jørgen 

TITLE=In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=8

YEAR=2016

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2016.00108

DOI=10.3389/fnagi.2016.00108

ISSN=1663-4365

ABSTRACT=<p>In animal models, the incretin hormone GLP-1 affects Alzheimer’s disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMR<sub>glc</sub>) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (<italic>n</italic> = 18), or placebo (<italic>n</italic> = 20). We measured Aβ load in brain with tracer [<sup>11</sup>C]PIB (PIB), CMR<sub>glc</sub> with [<sup>18</sup>F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe in placebo and treatment patients (both <italic>P</italic> = 0.04), and in occipital lobe in treatment patients (<italic>P</italic> = 0.04). Regional and global increases of PIB retention did not differ between the groups (<italic>P</italic> ≥ 0.38). In placebo treated patients CMR<sub>glc</sub> declined in all regions, significantly so by the following means in precuneus (<italic>P</italic> = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (<italic>P</italic> = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (<italic>P</italic> = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (<italic>P</italic> = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (<italic>P</italic> = 0.04, 1.54 μmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMR<sub>glc</sub> after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMR<sub>glc</sub> that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Aβ load or cognition measures, for which the study was underpowered.</p>