Approved research

Investigating the Causal Relationship Between Antiepileptic Drug Use and Dementia Onset: A Mendelian Randomization Study

Lay summary

Title: Investigating the Causal Relationship Between Antiepileptic Drug Use and Dementia Onset: A Mendelian Randomization Study

Background: The use of antiepileptic drugs (AEDs) is a critical component in the management of epilepsy, a neurological condition affecting millions worldwide. However, emerging evidence suggests a possible link between long-term AED use and the development of dementia. Dementia is a debilitating condition characterized by a decline in memory, language, problem-solving abilities, and other cognitive functions that interfere with daily life. While observational studies have suggested an association between AED use and increased dementia risk, these studies are prone to confounding factors and cannot establish causality. To address this gap, we propose to use Mendelian Randomization (MR), which leverages genetic variants as instruments to examine the causal effects of a risk factor (in this case, AED use) on an outcome (dementia onset) in a manner that is less susceptible to confounding.

Objective: To investigate whether there is a causal relationship between antiepileptic drug use and the onset of dementia using the UK Biobank data.

Methods: This study will employ a two-step approach to conduct a Mendelian Randomization analysis. First, we will identify genetic variants associated with the propensity to use antiepileptic drugs from large-scale genome-wide association studies (GWAS). These genetic variants will serve as instrumental variables for AED use. Second, we will utilize the UK Biobank dataset, which includes genetic and health-related information on over 500,000 individuals, to examine if these genetic variants are also associated with an increased risk of developing dementia. If the genetic variants associated with AED use are also associated with a higher risk of dementia, it would provide evidence supporting a causal relationship.

Significance: Understanding the causal link between AED use and dementia onset is crucial for patient care, particularly for individuals with epilepsy who may be at an increased risk of developing dementia. By clarifying this association, our study aims to inform clinical guidelines and strategies for monitoring and potentially mitigating dementia risk among epilepsy patients. Additionally, our findings could pave the way for further research into alternative therapeutic strategies that minimize dementia risk without compromising seizure control.

Timeline: We propose to complete this project within 36 months, allowing sufficient time for data analysis, interpretation of results, and dissemination of findings.