Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer´s disease - protocol for a controlled, randomized double-blinded trial

• Published in: Danish medical journal Vol. 59; no. 10; p. A4519
• Main Authors: Egefjord, Lærke, Gejl, Michael, Møller, Arne, Brændgaard, Hans, Gottrup, Hanne, Antropova, Olga, Møller, Niels, Poulsen, Henrik E, Gjedde, Albert, Brock, Birgitte, Rungby, Jørgen
• Format: Journal Article
• Language: English
• Published: Denmark 01.10.2012
• Subjects: Alzheimer Disease - diagnosis; Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Blood Flow Velocity - drug effects; Brain - metabolism; Brain - physiopathology; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cognition - drug effects; Cognition - physiology; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - analogs & derivatives; Humans; Liraglutide; Magnetic Resonance Imaging - methods; Positron-Emission Tomography; Treatment Outcome
• ISSN: 2245-1919

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. 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. 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. The trial is investigator-initiated and investigator-driven and is supported by Novo Nordisk Scandinavia. ClinicalTrials.gov: NCT01469351.