Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)

Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)

The aim of this study is to determine if lowering blood pressure using FDA approved medication (antihypertensive drugs) alters brain pulsatility and reduces brain amyloid beta protein accumulation in older adults. Amyloid beta protein is high in the brain of older adults with Alzheimer's disease. Hypertension may increase brain amyloid beta protein accumulation and affect memory and thinking ability in older adults. However, whether lowering blood pressure reduces brain amyloid beta protein and improves brain function is inconclusive.

The investigators hypothesize that treating high blood pressure alters brain pulsatility, which in turn reduces brain amyloid beta protein accumulation and improves brain structure and function.

Inclusion Criteria:

1. Age 55-79, all races/ethnicities, and both women and men are eligible;
2. Mini-mental state exam (MMSE) > 26 to exclude cognitive impairment or dementia;
3. Healthy normotensive subjects (24-hour ambulatory BP<125/75 mmHg without use of antihypertensive medication);
4. Patients with hypertension defined as 24-hour SBP ≥130 mmHg , patients on BP medications are eligible;
5. Patients with hypertension are willing to be randomized into either treatment group and ability to return to clinic or laboratory for follow-up visits over 12 months;
6. Fluency in English, adequate visual and auditory acuity to allow neuropsychological testing;
7. Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

Exclusion Criteria:

1. History of stroke, transient ischemic attack, traumatic brain injury or severe cerebrovascular disease by clinical diagnosis or past MRI/CT;
2. Diagnosis of AD or other type of dementia and neurodegenerative diseases;
3. Evidence of severe depression or other DSM-V Axis I psychopathology
4. Unstable heart disease based on clinical judgment (heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), evidence of atrial fibrillation on ECG, or other severe medical conditions;
5. Chronic kidney diseases with GFR < 40 ml/min;
6. Orthostatic hypotension, defined as standing SBP<100 mmHg;
7. History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica;
8. History of drug or alcohol abuse within the last 2 years;
9. Diagnosis of uncontrolled diabetes mellitus (fasting blood sugar ≥126 mg/dL or A1C >7.5%)
10. Obstructive sleep apnea;
11. Regularly smoking cigarette within the past year;
12. Severe obesity with BMI ≥ 45;
13. Participants enrolled in another investigational drug or device study within the past 2 months;
14. Carotid stent or sever stenosis (> 50%);
15. Pacemaker or other medical device of metal that precludes performing MRI;
16. History of B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable);
17. Any conditions judged by the study investigators to be either medically inappropriate, or risky for participant or likely to have poor study adherence;
18. Claustrophobia;
19. Pregnancy