candesartan vs lisinopril effects on the brain

Conditions: Hypertension; Mild Cognitive Impairment

Summary: the aim of this study is to conduct a 1-year double blind randomized control trial comparing candesartan to lisinopril in 140 individuals with hypertension and executive mild cognitive impairment in their effects on executive function, neuroimaging markers, and vascular indicators.

* hypertension is associated with cognitive impairment even in the absence of clinical dementia. to date, no specific treatment is available for this pattern of mild cognitive impairment related to hypertension. * objectives or purpose: the aims of this study are to investigate the effects of candesartan on executive function decline and on changes in cerebral perfusion, cerebrovascular reserve and microvascular brain injury. the study also intends to identify potential underlying mechanisms related to vascular structure and function, including atherosclerosis, vascular inflammation, vascular stiffness, and endothelial progenitor cells, by which candesartan may affect the cognitive and cerebrovascular outcomes. * study methodology:this is a double blind randomized clinical trial that will be conducted in 140 individuals (70 in the candesartan group, 70 in the lisinopril group). our target population is subjects: 55 years or older with hypertension and executive mild cognitive impairment. * endpoints to be measured:our measures include cognitive function, cerebral perfusion and reserve, markers of vascular brain damage, atherosclerosis, stiffness, vascular inflammation and endothelial function. * description of intervention, follow-up, and duration of study: eligible participants will undergo randomization into 2 groups and will be seen frequently until their blood pressure is controlled (\<140/90 mmhg). participants will be seen at 3, 6 and 12 months afterwards.

Eligibility criteria:
inclusion criteria: 1. age: 55 years or older; 2. hypertension: sbp≥140 mm hg or dbp≥ 90 mm or receiving antihypertensive medications. 3. executive mci will be defined using these criteria: 1. the montreal cognitive assessment (moca) score less than or equal to 26 2. executive dysfunction: a performance at the 10th percentile or below on at least one of four screening tests for executive function: trail making test, part b (tmt-b), modified stroop interference, digit span and digit sequencing, and letter fluency. 3. minimal functional limitation as reflected by the functional assessment questionnaire (faq)≤7 exclusion criteria: 1. intolerance to study drugs; 2. sbp \>200 or dbp \>110 mm hg; 3. renal disease or hyperkalemia 4. active medical or psychiatric problems 5. uncontrolled congestive heart failure; 6. history of stroke in the past 3 years; 7. inability to perform the study procedures 8. women of childbearing potential 9. diagnosis of dementia 10. in those who lack decision capacity, a study surrogate who can sign on their behalf will be required. since we are enrolling only those with mci, we anticipate that most participants will have decision capacity 11. current use of lithium, as most antihypertensive classes may lead to increased lithium toxic levels.

Keywords: cerebrovascular function