Harvard Medical School, Boston, MA, USA.
BMC Geriatr. 2009 Nov 18;9:48. doi: 10.1186/1471-2318-9-48.
Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments.
METHODS/DESIGN: The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity.
The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging.
Clinicaltrials.gov NCT00605072.
先前的证据表明，肾素-血管紧张素系统和抑制该系统的降压药在认知、中枢血管和内皮功能中发挥作用。我们的目标是进行一项双盲随机对照临床试验，即降压药与血管、内皮和认知功能（AVEC）研究，比较 3 种降压药（赖诺普利、坎地沙坦或氢氯噻嗪）治疗 1 年对高血压和早期有执行功能或记忆障碍客观证据的老年人记忆和执行功能、脑血流和中枢内皮功能的影响。
方法/设计：AVEC 试验的总体实验设计是一项 3 臂双盲随机对照临床试验。共有 100 名来自大波士顿地区的符合条件的社区老年人（60 岁或以上）患有高血压和早期认知障碍，他们正在接受招募，并随机分为赖诺普利、坎地沙坦或氢氯噻嗪（“活性对照”）组，接受 12 个月的治疗。干预的目标是实现血压控制，定义为 SBP<140mmHg 和 DBP<90mmHg。如果需要，还会添加其他降压药来达到这一目标。符合条件的参与者是那些患有高血压的人，定义为血压 140/90mmHg 或更高，早期认知障碍但没有痴呆症定义（执行时钟绘图测试得分为 10 或以下，或重复神经心理状况评估的即刻记忆子测试得分为 1 个标准差低于平均值，Mini-Mental-Status-exam>20，并且没有临床诊断为痴呆症或阿尔茨海默病）。如果参与者和初级保健提供者愿意逐渐减少他们的降压药，目前正在服用降压药的人也有资格参加。参与者接受认知评估、使用经颅多普勒测量脑血流以及通过测量基线时（停用降压药）、6 个月和 12 个月时二氧化碳终末呼气变化引起的脑血流变化来测量中枢内皮功能。我们的结果是认知功能评分（执行和记忆）、脑血流和二氧化碳脑血管反应性的变化。
AVEC 试验是第一项研究，旨在探讨在有早期认知困难但未达到痴呆阈值的人群中使用降压药的影响。该试验的成功将为抑制肾素-血管紧张素系统的降压药提供新的治疗应用，并为该系统在衰老中的作用提供新的见解。
Clinicaltrials.gov NCT00605072。
