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In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial
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(glc)) in AD. In this 26-week trial, we randomized 38 patients with...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877513/ https://www.ncbi.nlm.nih.gov/pubmed/27252647 http://dx.doi.org/10.3389/fnagi.2016.00108 |
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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 |
author_facet | 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 |
author_sort | Gejl, Michael |
collection | PubMed |
description | 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(glc)) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [(11)C]PIB (PIB), CMR(glc) with [(18)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 P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMR(glc) declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 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(glc) after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMR(glc) 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. |
format | Online Article Text |
id | pubmed-4877513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48775132016-06-01 In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial 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 Front Aging Neurosci Neuroscience 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(glc)) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [(11)C]PIB (PIB), CMR(glc) with [(18)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 P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMR(glc) declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 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(glc) after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMR(glc) 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. Frontiers Media S.A. 2016-05-24 /pmc/articles/PMC4877513/ /pubmed/27252647 http://dx.doi.org/10.3389/fnagi.2016.00108 Text en Copyright © 2016 Gejl, Gjedde, Egefjord, Møller, Hansen, Vang, Rodell, Brændgaard, Gottrup, Schacht, Møller, Brock and Rungby. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience 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 In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial |
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 |
title_full | In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial |
title_fullStr | In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial |
title_full_unstemmed | In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial |
title_short | In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial |
title_sort | in alzheimer’s disease, 6-month treatment with glp-1 analog prevents decline of brain glucose metabolism: randomized, placebo-controlled, double-blind clinical trial |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877513/ https://www.ncbi.nlm.nih.gov/pubmed/27252647 http://dx.doi.org/10.3389/fnagi.2016.00108 |
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