Molecular & Clinical Sciences Research Institute, St George's University of London, London, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.
Alzheimers Dement. 2022 Dec;18(12):2393-2402. doi: 10.1002/alz.12559. Epub 2022 Feb 8.
There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.
In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.
Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (-7.8, -4.9 mmHg; P < .001). No serious adverse events were observed.
This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.
血管性认知障碍（VCI）的随机临床试验较少。本试验检验了假设，即 PDE5 抑制剂他达拉非（一种广泛使用的血管扩张剂）可增加有症状小血管疾病（VCI 的主要病因）老年人的脑血流（CBF）。
在一项双盲、安慰剂对照、交叉试验中，参与者在两次访视（间隔至少 7 天）中接受他达拉非（20mg）和安慰剂（按治疗顺序随机分配）。主要终点是通过动脉自旋标记测量皮质下 CBF 的变化。
他达拉非可使所有皮质下区域的 CBF 非显著增加（N=55，年龄：66.8（8.6）岁），在白质高信号区的治疗效果最大（+9.8%，P=0.0960）。血压的收缩压和舒张压有偶然的治疗作用（-7.8，-4.9mmHg；P<0.001）。未观察到严重不良事件。
本试验未发现单次给予他达拉非对皮质下 CBF 有显著的治疗作用。要检测治疗效果可能需要不同的给药方案。
