CAndesartan vs LIsinopril Effects on the BRain

- 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: 60 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.

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 26

2. Clinical Dementia Rating (CDR) score of 0.5,

3. 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, verbal fluency (number of D words in 1
minute), or abstractions.

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