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.
abstract: 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 (CMRglc) 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), CMRglc 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 CMRglc 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 CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc 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.
authors.affiliation: Institute of Biomedicine, Aarhus UniversityAarhus, Denmark; Department of Nuclear Medicine and PET Center, Aarhus University HospitalAarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Gejl
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University HospitalAarhus, Denmark; Department of Neuroscience and Pharmacology, University of CopenhagenCopenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Institute of Biomedicine, Aarhus UniversityAarhus, Denmark; Department of Nuclear Medicine and PET Center, Aarhus University HospitalAarhus, Denmark.
authors.forename: Lærke
authors.initials: L
authors.lastname: Egefjord
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Søren B
authors.initials: SB
authors.lastname: Hansen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Vang
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Rodell
authors.affiliation: Dementia Clinic, Department of Neurology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Brændgaard
authors.affiliation: Dementia Clinic, Department of Neurology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Gottrup
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Schacht
authors.affiliation: Department of Endocrinology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.affiliation: Institute of Biomedicine, Aarhus UniversityAarhus, Denmark; Department of Clinical Biochemistry, Aarhus University HospitalAarhus, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.affiliation: Institute of Biomedicine, Aarhus UniversityAarhus, Denmark; Center for Diabetes Research and Department of Clinical Pharmacology, Copenhagen University Hospital Gentofte and RigshospitaletCopenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
keywords: Alzheimer’s disease; amyloid; cerebral glucose metabolism; glucagon-like peptide-1; liraglutide