2025 American Academy of Neurology Abstract Website

Objective:

This comprehensive retrospective cohort study seeks to assess the impact of GLP-1 Agonists on various neurodegenerative conditions.

Background:

GLP-1 Agonists have been historically used as a potential treatment for type 2 diabetes mellitus and recent review supports that these medications also have a therapeutic impact on obesity. Some of the most pertinent GLP-1 Agonists, Dulaglutide, liraglutide, and semaglutide, also exhibit anti-inflammatory properties although their role in neurodegenerative disorders such as Alzheimer’s and Parkinson’s is not yet fully understood.

Design/Methods:

This comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients and 2,122,880 controls across 73 healthcare organizations. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not.

Results:

Obese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Parkinson's disease (RR=0.784, 95%CI=0.580-1.058), Alzheimer's dementia (RR=0.627, 95%CI=0.481-0.817), amyotrophic lateral sclerosis (RR=0.833, 95%CI=0.360-1.929), Lewy body dementia (RR=0.590, 95%CI=0.462-0.753), multiple sclerosis (RR=0.574, 95%CI=0.358-0.922), vascular dementia (RR=0.438, 95%CI=0.327-0.588), and Wilson's disease (RR=0.833, 95%CI=0.360-1.929). Additionally, a significant reduction in mortality was observed (HR=0.525, 95%CI=0.493-0.558).

Conclusions:

This study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.