| Summary: | Abstract Objective Phosphodiesterase‐5 inhibitors (PDE5Is) enhance vasodilation. We investigated the effects of PDE5I on cerebral hemodynamics during cognitive tasks using functional near‐infrared spectroscopy (fNIRS). Methods This study used a crossover design. Twelve cognitively healthy men participants (mean age, 59 ± 3 years; range, 55–65 years) were recruited and randomly assigned to the experimental or control arm, then the experimental and control arm were exchanged after 1 week. Udenafil 100 mg was administered to participants in the experimental arm once daily for 3 days. We measured the fNIRS signal during the resting state and four cognitive tasks three times for each participant: at baseline, in the experimental arm, and in the control arm. Results Behavioral data did not show a significant difference between the experimental and control arms. The fNIRS signal showed significant decreases in the experimental arm compared to the control arm during several cognitive tests: verbal fluency test (left dorsolateral prefrontal cortex, T = −3.02, p = 0.014; left frontopolar cortex, T = −4.37, p = 0.002; right dorsolateral prefrontal cortex, T = −2.59, p = 0.027), Korean‐color word Stroop test (left orbitofrontal cortex, T = −3.61, p = 0.009), and social event memory test (left dorsolateral prefrontal cortex, T = −2.35, p = 0.043; left frontopolar cortex, T = −3.35, p = 0.01). Interpretation Our results showed a paradoxical effect of udenafil on cerebral hemodynamics in older adults. This contradicts our hypothesis, but it suggests that fNIRS is sensitive to changes in cerebral hemodynamics in response to PDE5Is.
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