Cilostazol Use Is Associated with Reduced Risk of Dementia: A Nationwide Cohort Study

Whether antiplatelet agents have a preventive effect on cognitive function remains unknown. We examined the potential association between the use of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, and the risk of dementia in an Asian population. Patients initiating cilostazol therapy between 1 January 2004 and 31 December 2009 without a prior history of dementia were identified from Taiwan's National Health Insurance database. Participants were stratified by age, sex, comorbidities, and comedication. The outcome of interest was all-cause dementia (ICD-9CM codes 290.0, 290.4, 294.1, 331.0). Cox regression models were used to estimate the hazard ratio (HR) of dementia. The cumulative cilostazol dosage was stratified by quartile of defined daily doses using no cilostazol use as a reference. A total of 9148 participants 40 years of age or older and free of dementia at baseline were analyzed. Patients using cilostazol (n = 2287) had a significantly decreased risk of incident dementia compared with patients not using the drug [n = 6861; adjusted HR (aHR) 0.75; 95% confidence interval (CI) 0.61-0.92]. Notably, cilostazol use was found to have a dose-dependent association with reduced rate of dementia emergence (p for trend = 0.001). Subgroup analysis identified a decline of dementia in cilostazol users with diagnosed ischemic heart disease (aHR 0.44, 95% CI 0.24-0.83) and cerebral vascular disease (aHR 0.34, 95% CI 0.21-0.54). These observations suggest that cilostazol use may reduce the risk to develop dementia, and a high cumulative dose further decreases the risk of dementia. These findings should be examined further in randomized clinical trials.