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

Lærke Egefjord, Michael Gejl, Arne Møller, Hans Brændgaard, Hanne Gottrup, Olga Antropova, Niels Møller, Henrik E. Poulsen, Albert Gjedde, Birgitte Brock, Jørgen Rungby

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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 investigatordriven and is supported by Novo Nordisk Scandinavia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01469351.

Original languageEnglish (US)
JournalDanish Medical Journal
Volume59
Issue number10
StatePublished - 2012
Externally publishedYes

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Cognition
Alzheimer Disease
Positron-Emission Tomography
Central Nervous System
Islet Amyloid Polypeptide
Scandinavian and Nordic Countries
Glucose
Psychological Tests
Glucagon-Like Peptide 1
Magnetic Resonance Angiography
Brain Diseases
Liraglutide
Amyloid
Type 2 Diabetes Mellitus
Pancreas
Placebos
Research Personnel
Brain
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

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Egefjord, L., Gejl, M., Møller, A., Brændgaard, H., Gottrup, H., Antropova, O., ... Rungby, J. (2012). Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer's disease - Protocol for a controlled, randomized double-blinded trial. Danish Medical Journal, 59(10).

Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer's disease - Protocol for a controlled, randomized double-blinded trial. / Egefjord, Lærke; Gejl, Michael; Møller, Arne; Brændgaard, Hans; Gottrup, Hanne; Antropova, Olga; Møller, Niels; Poulsen, Henrik E.; Gjedde, Albert; Brock, Birgitte; Rungby, Jørgen.

In: Danish Medical Journal, Vol. 59, No. 10, 2012.

Research output: Contribution to journalArticle

Egefjord, L, Gejl, M, Møller, A, Brændgaard, H, Gottrup, H, Antropova, O, Møller, N, Poulsen, HE, Gjedde, A, Brock, B & Rungby, J 2012, 'Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer's disease - Protocol for a controlled, randomized double-blinded trial', Danish Medical Journal, vol. 59, no. 10.
Egefjord, Lærke ; Gejl, Michael ; Møller, Arne ; Brændgaard, Hans ; Gottrup, Hanne ; Antropova, Olga ; Møller, Niels ; Poulsen, Henrik E. ; Gjedde, Albert ; Brock, Birgitte ; Rungby, Jørgen. / Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer's disease - Protocol for a controlled, randomized double-blinded trial. In: Danish Medical Journal. 2012 ; Vol. 59, No. 10.
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AU - Gejl, Michael

AU - Møller, Arne

AU - Brændgaard, Hans

AU - Gottrup, Hanne

AU - Antropova, Olga

AU - Møller, Niels

AU - Poulsen, Henrik E.

AU - Gjedde, Albert

AU - Brock, Birgitte

AU - Rungby, Jørgen

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N2 - 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 investigatordriven and is supported by Novo Nordisk Scandinavia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01469351.

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