“Treating Cognitive Impairment in Schizophrenia With GLP-1RAs: an Overview of Their Therapeutic Potential”, 2021-07-09 ():
Background: Schizophrenia is a neuropsychiatric disorder that affects ~1% of individuals worldwide. There are no available medications to treat cognitive impairment in this patient population currently. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cognitive function. There is a need to evaluate how GLP-1 RAs alter specific domains of cognition and whether they will be of therapeutic benefit in individuals with schizophrenia.
Areas covered: This paper summarizes the effects of GLP-1 RAs on metabolic processes in the brain and how these mechanisms relate to improved cognitive function. We provide an overview of preclinical studies that demonstrate GLP-1 RAs improve cognition and comment on their potential therapeutic benefit in individuals with schizophrenia.
Expert Opinion: To understand the benefits of GLP-1 RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1 RAs. Further research into the specific mechanisms of how GLP-1 RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.
[Keywords: Glucagon-like peptide-1 receptor agonists, liraglutide, exenatide, cognition, metabolism, metabolic dysregulation, schizophrenia, translational assays, memory, executive function]
Individuals with schizophrenia experience an increased incidence of metabolic dysfunction that co-occurs with cognitive impairment.
GLP-1RAs are currently used to reduce metabolic side-effects caused by antipsychotics. However, further investigation is required to assess whether they can improve cognition in individuals with schizophrenia.
Preclinical testing of GLP-1RAs in animal models that recapitulate key cognitive deficits in schizophrenia is needed. We suggest that future studies should use translational rodent assays such as touch-screen testing to investigate the effects of GLP-1RAs on executive function, attention, and working memory.
Adjunctive treatment with other antipsychotic medication may offer an effective strategy to counter weight-gain and improve cognitive status in individuals with schizophrenia. Further research is required to understand whether newer GLP-1RAs are effective in reducing weight and improving cognition.