title: Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer´s disease - protocol for a controlled, randomized double-blinded trial.
abstract: BACKGROUND
  Type 2 diabetes (DM-2) increases the risk of developing Alzheimer´s disease (AD), and patients with AD are more likely to develop DM-2. DM-2 and AD share some pathophysiological features. In AD, amyloid-β (Aβ) is accumulated as extracellular plaques in the gray matter of the brain, while in DM-2 islet amyloid polypeptide (IAPP) is accumulated in the pancreas. Premature cellular degeneration is seen in both diseases. Glucagon-like peptide-1 (GLP-1) reduces the amount of Aβ and improves cognition in animal studies. The present study tests the hypothesis that treatment with the long-acting GLP-1 receptor agonist liraglutide affects the accumulation of Aβ in patients with AD.
  
  
  METHODS
  This is a randomized, controlled, double-blinded intervention study with AD patients treated for six months with liraglutide (n = 20) or placebo (n = 20). The primary outcome is change in deposition of Aβ in the central nervous system (CNS) by Pittsburgh compound B positron emission tomography (PET). The secondary outcome is evaluation of cognition using a neuro-psychological test battery, and examination of changes in glucose uptake in the CNS by 18F-fluoro-deoxy-glucose PET. Finally, a perfusion-weighted magnetic resonance imaging with contrast will be performed to evaluate blood flow.
  
  
  CONCLUSIONS
  No registered drug affects the deposition of Aβ in the brain of AD patients. Our goal is to find a new therapeutic agent that alters the pathophysiology in AD patients by decreasing the formation of Aβ plaques and thereby presumably improves the cognitive function.
  
  
  BACKGROUND
  The trial is investigator-initiated and investigator-driven and is supported by Novo Nordisk Scandinavia.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01469351.
authors.affiliation: Institute of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. laerke.egefjord@farm.au.dk
authors.forename: Lærke
authors.initials: L
authors.lastname: Egefjord
authors.forename: Michael
authors.initials: M
authors.lastname: Gejl
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.forename: Hans
authors.initials: H
authors.lastname: Brændgaard
authors.forename: Hanne
authors.initials: H
authors.lastname: Gottrup
authors.forename: Olga
authors.initials: O
authors.lastname: Antropova
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001783:Blood Flow Velocity / Q000187:drug effects*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D000069450:Liraglutide; D008279:Magnetic Resonance Imaging / Q000379:methods; D049268:Positron-Emission Tomography; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1