Exploring the Neural Substrates of Cognitive Dysfunction With Glucagon-like Peptide-1 Agonists

Clinical trial identifier: NCT02423824

 

Rationale:          

Cognitive deficits are a core feature across disparate brain disorders, being highly prevalent and pervasive. Cognitive dysfunction is thought to be underlied by abnormalities in distributed brain circuits. The neural mechanisms underlying the dysregulation in these circuits are poorly understood. Emerging evidence indicates that metabolic abnormalities are highly relevant for the domain of cognitive function and indicate that alterations in metabolic pathways may be relevant to neurocognitive decline across different populations. We hypothesize that GLP-1 and the GLP-1R are relevant for molecular and cellular processes that are thought to underlie the formation and maintenance of brain circuits.

 

Primary Objective:

The overall goal of this study is to explore the relationship between a metabolic molecular target (i.e. the GLP1 system), the neural circuits of interest and the behavioral phenotype cognitive function.
 

Study Design:   

We will select a subpopulation of patients, with a mood disorder and impairment in executive function, as defined by a below-average (i.e. 1 standard deviation below norm) performance in the Trail Making Test-B (TMTB). Furthermore, we plan to recruit two groups of patients, with and without insulin resistance, as defined by a homeostatic model assessment for insulin resistance (HOMA-IR) above 2.5, which will allow a comparison of the effects of liraglutide in a metabolically heterogeneous population.