GLP-1 therapies and cognitive impairment: New data highlights possible “survival paradox”

Isaac Thorman, Fawaz Al-Muft — AAN2026

Findings from AAN 2026 highlight a potential “survival paradox” associated with GLP-1 analogue use in older adults with diabetes

At American Academy of Neurology 2026, Isaac Thorman (New York Medical College, Valhalla, NY, USA) presented new real-world data exploring the relationship between GLP-1 receptor agonists, cognitive impairment and mortality in older adults with Type 2 diabetes mellitus.

The analysis, conducted under the supervision of principal investigator and senior author Prof. Fawaz Al-Mufti (Triple board-certified neurologist, neurointensivist and neurointerventionalist, Associate Dean for Research and Innovation, and Vice Chair of Neurology (Research), New York Medical College, and Director of the Center for Neurological Research and Innovation at Westchester Medical Center, NY, USA;), drew on large-scale longitudinal data and highlighted the importance of interpreting potential cognitive risk within the context of longer survival among patients receiving GLP-1 therapies. This interview brings both perspectives together to discuss the data and a look to the future.

Presented at AAN 2026: Long-Term Risk of Cognitive Impairment with GLP-1 Analogues in Older Adults with Type 2 Diabetes Mellitus. LS1: Late-breaking Science 1. April 18-22, Chicago, USA.

Could you briefly introduce yourself and explain the background to this research?

Introducing the background to the study, Isaac Thorman explained: “I am a rising fourth-year medical student at New York Medical College. I completed my undergraduate studies at Wesleyan University with a background in neuroscience, and then completed a master’s degree in epidemiology at Johns Hopkins University.

Coming into medical school, I knew I wanted to pursue neurology, so I have been working with Prof. Fawaz Al-Mufti (New York Medical College, Valhalla, NY, USA) and others on projects related to cognitive impairment, traumatic brain injury and care for critically ill patients.

As GLP-1 receptor agonists have become increasingly popular, there have been growing questions about their long-term effects. Semaglutide (Ozempic, Novo Nordisk) has only been available for a few years, and although other agents have since entered the market, these therapies have really only been widely used since around 2017 and became especially popular following the COVID-19 pandemic.

What has been striking is the broad range of protective effects being reported. These medications were originally developed for diabetes and obesity, which are major public health problems in the US, the UK and globally, but the effects being observed extend far beyond metabolic disease. Clinical trials are now exploring GLP-1 therapies in conditions ranging from cancer to epilepsy.

The cognitive and cerebrovascular effects, however, remain less clear. A recent trial published in The Lancet, the EVOKE trial, evaluated whether GLP-1 analogues could reduce the burden of Alzheimer disease and mild cognitive impairment in older adults. Although biomarker improvements were observed, there was no significant clinical difference in cognitive outcomes between patients receiving GLP-1 analogues and controls.”

Commenting on the rationale for the study, Prof. Al-Mufti noted: “GLP-1 therapies are rapidly reshaping the management of diabetes, obesity and cardiometabolic disease. As these agents move into broader and older patient populations, it becomes increasingly important to understand not only their metabolic and cardiovascular effects, but also their potential long-term neurologic associations.”

Isaac Thorman added: “This is where our study comes in. We are dealing with a growing public health burden of cerebrovascular disease, diabetes and obesity in an aging population. The risk of cognitive impairment is elevated in patients with diabetes and obesity, and GLP-1 therapies have tremendous potential in this area. However, the clinical data remain mixed, so our objective was to examine whether GLP-1 analogue use may modify the risk of cognitive impairment in patients with type 2 diabetes.”

Could you explain the study design and how you evaluated the relationship between GLP-1 analogue use and cognitive impairment?

Discussing the study methodology, Isaac Thorman said: “We used the TriNetX Research Network, which is a federated database containing longitudinal health data from more than 100 healthcare organizations and approximately 160 million patients. The platform includes diagnoses, medications, laboratory tests and procedures recorded longitudinally over time.

We included patients aged 50 years and older with Type 2 diabetes mellitus and followed them for up to 10 years to assess the development of cognitive impairment. Patients with pre-existing cognitive impairment or cerebrovascular disease prior to treatment initiation were excluded.

We defined cognitive impairment using a composite outcome including mild cognitive impairment, Alzheimer disease and vascular dementia. Mortality was also included as a key outcome because these medications appear to have substantial cardiovascular benefits that may prolong survival.

A major strength of the study was the propensity score matching approach. We matched patients on more than 170 characteristics, including demographics, BMI, laboratory data, comorbidities and medication use, to create comparable groups of GLP-1 recipients and non-recipients. The goal was to mimic, as closely as possible, the balance achieved in a randomized controlled trial.

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