Conditions: Cognitive Impairment Hypertension Aging
Keywords: cognitive disorders angiotensin receptor blockers
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 53
Healthy volunteers: no

Brief summary:
The purpose of this study is to examine the effects of blood pressure medications on cognition and blood flow in hypertensive elderly patients with cognitive impairment. The hypothesis is that treatment with an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEI) will be associated with a slower rate of further cognitive decline, improved cerebral blood flow and its regulation, and preserved physical function as compared to treatment with a diuretic (HCTZ), independent of blood pressure level.

Detailed description:
There is mounting evidence that hypertension, which affects more than 65% of the US elderly population, accelerates cognitive decline and increases the risk of functional disability among older individuals. Hypertension is also associated with cerebral blood flow reduction and dysregulation which contribute to further cognitive and functional impairment. Drugs that inhibit angiotensin II (ACEI and ARB) are commonly used antihypertensives and may have a protective effect on cognitive function, cerebral blood flow and physical function compared to other antihypertensives such as hydrochlorothiazide (HCTZ).

A total of 100 individuals will be recruited for this pilot 3-arm randomized study to investigate the effects of: (i) 12 months treatment with candesartan (ARB) compared to hydrochlorothiazide (HCTZ) and (ii) 12 months treatment with lisinopril (ACEI) compared to HCTZ and (iii) to estimate the effect size difference between lisinopril and losartan on cognition, cerebral blood flow regulation, and functional measures in a sample of elderly hypertensive individuals with objective evidence of cognitive impairment.

Arms:
arm 1: Angiotensin Receptor Blocker arm 2: Angiotensin-Converting Enzyme (ACE) Inhibitor arm 3: Hydrochlorothiazide (diuretic)

Interventions: intervention 1: candesartan intervention 2: lisinopril intervention 3: hydrochlorothiazide intervention 4: nifedipine, long acting intervention 5: metoprolol, long-acting
Intervention descriptions: intervention 1: orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months intervention 2: orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months intervention 3: orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months intervention 4: If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments intervention 5: If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Protocol document: