Repurposing probucol for prevention of dementia: a nationwide cohort study

<title>Abstract</title> <p>Background Effective treatments for neurodegenerative disease remain elusive, highlighting the importance of prevention. Probucol, a lipid-lowering antioxidant, is neuroprotective in preclinical models but untested for dementia in large populations. Methods Using the Japan Medical Data Centre claims database (2014–2023), adults aged ≥ 50 years prescribed probucol or statins were identified. Propensity score matching produced a stacked cohort of 52,532 individuals. Conditional logistic regression estimated odds ratios (ORs) for incident all-cause dementia and subtypes, adjusted for age and sex; stratified Cox models accounted for follow-up time. Results Probucol use was associated with approximately 51% lower odds of all-cause dementia than statins combined (adjusted OR 0.48, 95% CI 0.45–0.53). Associations were consistent across statins (adjusted ORs 0.40–0.66), Alzheimer’s disease, and vascular dementia. Sensitivity analyses were comparable (adjusted HR 0.50, 95% CI 0.45–0.56). Conclusions In this nationwide cohort, probucol use was associated with substantially lower dementia risk than statins, supporting evaluation of probucol for repurposing in dementia prevention.</p>