Real-world Observations on Neuroinflammation-related Drug Responses in Alzheimer’s Disease

Abstract

Background: Alcohol use disorder (AUD), epilepsy, hemorrhagic stroke (HS), and traumatic brain injury (TBI) are all linked to neuroinflammation and associated with an increased risk of Alzheimer’s disease (AD). Drug responses in cognitive health remain largely unknown in patients with neuroinflammation-related conditions. Objective: To investigate the associations between drug exposure and AD incidence in patients with neuroinflammation-related conditions. Methods: We derived covariate matched cohorts for individuals with and without neuroinflammation-related conditions (e.g., AUD, epilepsy, HS and TBI) from a US nationwide insurance claim data. We used covariate-adjusted Cox models to estimate the hazard ratios (HRs) of drug exposure on AD. We identified neuroinflammation-specific drug responses by comparing HRs between individuals with and without neuroinflammation-related conditions. Results: We identified 0.4 million matched pairs of individuals with and without neuroinflammation-related conditions. We identified three drugs (levothyroxine [HR =0.89], mirabegron [HR =0.69], and ropinirole [HR =0.81]) had a lower HR and two drugs (levetiracetam [HR =1.19], and quetiapine [HR =1.83]) had a higher HR in individuals with neuroinflammation-related conditions compared to without (false discovery rate <0.05). Conclusions: In patients with neuroinflammation-related conditions, we identified drugs associated with lower risks (levothyroxine, mirabegron and ropinirole) and higher risks (levetiracetam and quetiapine) of AD incidence.