Exploring the link between GLP-1 receptor agonists and dementia: A comprehensive review

Type 2 diabetes mellitus (T2DM) and insulin resistance are associated with an increased risk of cognitive decline and dementia, including Alzheimer's disease (AD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for glycemic control, are emerging as neuroprotective agents. This review evaluates the evidence regarding the effects of GLP-1RAs in populations with T2DM-both with and without cognitive impairment, as well as in individuals diagnosed with AD. We conducted a comprehensive literature search and identified ten studies for inclusion: six randomized controlled trials, one prospective open-label study, and three observational studies. GLP-1RAs consistently demonstrated cognitive benefits in patients with T2DM, even in the absence of metabolic improvements. In cases of early dementia or AD, GLP-1RA treatment preserved brain metabolism and connectivity but did not significantly alter amyloid or tau biomarkers. Notably, cognitive improvements were most evident in individuals with higher body mass index (BMI) or obesity. While some studies reported neural functional changes via imaging, direct modifications in established AD biomarkers were not consistently observed. In conclusion, GLP-1RAs may improve cognitive outcomes and brain function, particularly in the early stages of neurodegeneration and among high-risk T2DM populations. Further well-designed clinical trials are needed to evaluate the impacts of GLP-1RAs on both the clinical progression and underlying pathology of dementia.