Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's

High blood pressure (BP) in midlife is predictive of Alzheimer's disease (AD) in later life. Similarly, reductions in BP are associated with protection against AD. Treatment with antihypertensive medications, specifically angiotensin converting enzyme inhibitors (ACE-I) such as ramipril, is associated with up to a 55% reduction in the prevalence of AD, suggesting a potentially promising role for ACE-I in the prevention of AD. It is unknown however 1) whether ACE-Is will have the same effect on Cerebrospinal fluid (CSF) Aβ levels in humans as in animal models 2) whether ACE-Is induce changes associated with vascular function (i.e. levels of CSF angiotensin converting enzyme (ACE) and peripheral endothelial function) and 3) whether there are interactions between ACE-I-induced changes in CSF Aβ, CSF ACE and indices of vascular function.

One mechanism by which antihypertensives may protect against AD is via Aβ neuropathology. In order to better understand the mechanisms through which ACE-I may modify CSF Aβ and possibly AD risk, we propose a randomized, double-blind, placebo-controlled pilot clinical trial, enrolling 20 middle-aged (age range 40 - 65 years), mildly hypertensive (between 130 - 160 mmHg mean systolic and between 85 - 100 mmHg mean diastolic) participants, who are adult children of an individual with AD. The main objective of this trial is to examine the effects of the ACE-I, ramipril, on 1) CSF Aβ levels 2) CSF ACE levels and 3) peripheral endothelial function as measured by brachial artery flow-mediated vasodilation (FMD) and aortic augmentation index (AAIx), in middle-aged adults with mildly elevated BP, who are at increased risk of developing AD.

Inclusion criteria

• Between the ages of 40 and 65
• Mean resting blood pressure between 130-160 systolic and 85-100 diastolic
• Parent with Alzheimer's Disease

Exclusion criteria

• Current involvement in another investigational drug trial.
• Potassium > 5.0
• Dementia based on DSMIV criteria
• Mini-Mental State Exam (MMSE) score < 27
• Current blood pressure medication (< 4 months from screening)
• Weight loss medication
• Contraindications for LP
• Know diagnosis or history of hospitalization due to congestive heart failure
• Elevated creatinine (females > 1.3 mg/dL or males > 1.4 mg/dL at baseline)
• Diabetes Type I and II
• Know adverse reaction to an ACE-I or an angiotensin receptor blocker
• Pregnant of nursing women