Insulin resistance (IR) is a metabolic state preceding development of type 2 diabetes (DM2), cardiovascular disease, and neurodegenerative disorders, including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP) agonist, is an insulin-sensitizing agent with neuroprotective properties, as shown in animal studies. The purpose of this double-blinded, placebo-controlled study was to examine the neural effects of administration of liraglutide in cognitively normal late middle-aged individuals with subjective cognitive complaints (half of subjects had family history of AD). Seed-based resting state connectivity using functional magnetic resonance imaging (fMRI) was conducted before and after 12 weeks of liraglutide treatment or placebo. Neuropsychological testing was conducted before and after treatment to determine whether there were any potential behavioral correlates to neural changes. RESULTS: At baseline (time point 1), higher fasting plasma glucose (FPG) was associated with decreased connectivity between bilateral hippocampal and anterior medial frontal structures. At time point 2, we observed significant improvement in intrinsic connectivity within the default mode network (DMN) in the active group relative to placebo. There were no detectable cognitive differences between study groups after this duration of treatment. To our knowledge, this is the first placebo-controlled study to report neural effects of liraglutide in a middle-aged population with subjective cognitive complaints. Larger and longer duration studies are warranted to determine whether liraglutide has neuroprotective benefits in individuals at risk for AD.
RCT Entities:
Insulin resistance (IR) is a metabolic state preceding development of type 2 diabetes (DM2), cardiovascular disease, and neurodegenerative disorders, including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP) agonist, is an insulin-sensitizing agent with neuroprotective properties, as shown in animal studies. The purpose of this double-blinded, placebo-controlled study was to examine the neural effects of administration of liraglutide in cognitively normal late middle-aged individuals with subjective cognitive complaints (half of subjects had family history of AD). Seed-based resting state connectivity using functional magnetic resonance imaging (fMRI) was conducted before and after 12 weeks of liraglutide treatment or placebo. Neuropsychological testing was conducted before and after treatment to determine whether there were any potential behavioral correlates to neural changes. RESULTS: At baseline (time point 1), higher fasting plasma glucose (FPG) was associated with decreased connectivity between bilateral hippocampal and anterior medial frontal structures. At time point 2, we observed significant improvement in intrinsic connectivity within the default mode network (DMN) in the active group relative to placebo. There were no detectable cognitive differences between study groups after this duration of treatment. To our knowledge, this is the first placebo-controlled study to report neural effects of liraglutide in a middle-aged population with subjective cognitive complaints. Larger and longer duration studies are warranted to determine whether liraglutide has neuroprotective benefits in individuals at risk for AD.
Authors: T D Müller; B Finan; S R Bloom; D D'Alessio; D J Drucker; P R Flatt; A Fritsche; F Gribble; H J Grill; J F Habener; J J Holst; W Langhans; J J Meier; M A Nauck; D Perez-Tilve; A Pocai; F Reimann; D A Sandoval; T W Schwartz; R J Seeley; K Stemmer; M Tang-Christensen; S C Woods; R D DiMarchi; M H Tschöp Journal: Mol Metab Date: 2019-09-30 Impact factor: 7.422
Authors: Giulia Monti; Diana Gomes Moreira; Mette Richner; Henricus Antonius Maria Mutsaers; Nelson Ferreira; Asad Jan Journal: Cells Date: 2022-06-25 Impact factor: 7.666
Authors: Maria Vargas-Soria; Maria Jose Carranza-Naval; Angel Del Marco; Monica Garcia-Alloza Journal: Alzheimers Res Ther Date: 2021-06-12 Impact factor: 6.982