Baptist Health Center for Clinical Research, Little Rock, Arkansas, United States of America.
PLoS One. 2023 Oct 18;18(10):e0292863. doi: 10.1371/journal.pone.0292863. eCollection 2023.
Phosphodiesterase-5 inhibitors (PDE5i) have been evaluated as a novel treatment for Alzheimer's disease and related dementias (ADRD), but two recent cohort studies have offered opposing conclusions.
We performed an unmatched case-control study using electronic medical records from a large healthcare system to evaluate the association of PDE5i use and ADRD in patients ≥65 years old.
Odds of PDE5i exposure were 64.2%, 55.7%, and 54.0% lower in patients with ADRD than controls among populations with erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension, respectively. We observed odds ratios less than unity among males and females and with exposure to the PDE5i sildenafil (Viagra®) and tadalafil (Cialis®). We also evaluated the odds of exposure to two other common treatments for pulmonary hypertension: endothelin receptor antagonists (ERA) and calcium channel blockers (CCB). The odds of ERA exposure were 63.2% lower, but the odds of CCB exposure were 30.7% higher, in patients with ADRD than controls among the population with pulmonary hypertension.
Our results reconcile the opposing conclusions from the previous observational studies and support further research into using PDE5i for prevention and treatment of ADRD.
磷酸二酯酶-5 抑制剂（PDE5i）已被评估为治疗阿尔茨海默病和相关痴呆症（ADRD）的一种新方法，但最近的两项队列研究得出了相反的结论。
我们使用大型医疗保健系统的电子病历进行了一项非匹配病例对照研究，以评估 PDE5i 使用与 65 岁及以上患者 ADRD 的相关性。
与对照组相比，患有勃起功能障碍、良性前列腺增生和肺动脉高压的 ADRD 患者中 PDE5i 暴露的可能性分别降低了 64.2%、55.7%和 54.0%。我们观察到男性和女性以及暴露于 PDE5i 西地那非（伟哥®）和他达拉非（Cialis®）的比值小于 1。我们还评估了肺动脉高压的另外两种常见治疗方法：内皮素受体拮抗剂（ERA）和钙通道阻滞剂（CCB）的暴露可能性。与对照组相比，患有 ADRD 的肺动脉高压患者中，ERA 暴露的可能性降低了 63.2%，但 CCB 暴露的可能性增加了 30.7%。
我们的结果调和了先前观察性研究的相反结论，并支持进一步研究使用 PDE5i 预防和治疗 ADRD。
