Conversion from cilostazol to OPC-13015 linked to mitigation of cognitive impairment

Abstract

Introduction: Cilostazol may be a novel therapeutic agent for Alzheimer's disease. Its metabolite, OPC-13015, has a stronger inhibitory effect on type 3 phosphodiesterase than cilostazol. Methods: We prospectively enrolled patients with mild cognitive impairment to whom cilostazol was newly prescribed. Patients underwent the Montreal Cognitive Assessment (MoCA) twice, at a 6-month interval. Plasma cilostazol, OPC-13015, OPC-13213, and OPC-13217 concentrations were determined using liquid chromatography-tandem mass spectrometry. Results: MoCA score changes from baseline to the 6-month visit were positively correlated with ratios of OPC-13015 to cilostazol and total metabolites (n = 19, P =.005). Patients with higher ratios of OPC-13015 (≥0.18, median value; n = 10) had significantly higher MoCA scores (P =.036) than patients with lower ratios (the ratio <0.18, n = 9). The absolute value of OPC-13015 concentration in blood was also higher in patients with preserved cognitive function (P =.033). Discussion: Blood OPC-13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.