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

Authors
Lærke Egefjord1, Michael Gejl1, Arne Møller2, Hans Brændgaard3, Hanne Gottrup3, Olga Antropova4, Niels Møller5, Henrik E. Poulsen6,Albert Gjedde2, Birgitte Brock1 & Jørgen Rungby1, 1) Institute of Biomedicine, Aarhus University2) PET Center, Aarhus University Hospital3) Dementia Clinic, Department of Neurology, Aarhus University Hospital4) Department of Neurology, Viborg Hospital5) MEA, Aarhus University Hospital6) Laboratory of Clinical Pharmacology, Q7642, Rigshospitalet

Abstract

Introduction: 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.

Material and 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.

Conclusion: 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.

Funding: The trial is investigator-initiated and investigator-driven and is supported by Novo Nordisk Scandinavia. .

Trial registration: ClinicalTrials.gov: NCT01469351.

Over the past few years, a vast increase in the incidence of both type 2 diabetes (DM-2) and Alzheimer’s disease (AD) has been observed, leading to increased morbidity and mortality. Epidemiologically and pathophysiologically, DM-2 and AD share several features. DM-2 increases the risk of AD and vascular dementia two to five fold [1, 2]. It has been suggested that the risk correlates with plasma glucose [2] and hyperinsulinaemia in the early stages of DM-2 [1]. There is an increased incidence of DM-2 in patients with AD [3]. In both diseases, premature cell degeneration occurs....
Bib ref: 
Dan Med J 2012;59(10):A4519
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