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

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