Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study)

- Age 60-80, all races/ethnicities, and both sexes are eligible;

- a) A positive family history of dementia defined as having at least one first-degree relative with a history of AD or other type of dementia or

- b) having subjective memory complaints defined as a positive answer to BOTH of the following questions:

- Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical judgment, may be rescreened in ≥ 7 days;

- Individuals with SBP ≥ 130 and SBP ≤ 180; Those on antihypertensives are eligible. If an individual, not treated for HTN, has a SBP ≥ 125 mmHg, consider rescreening after 24 hours;

- Willingness to be randomized into the treatment groups and ability to return to clinic for follow-up visits over 24 months;

- Fluency in English or Spanish or both, adequate visual and auditory acuity to allow neuropsychological testing;

- Participants must have a regular healthcare provider.

- Clinically documented history of stroke, focal neurological signs or other major cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence of infection, infarction, or other brain lesions;

- Diagnosis of AD or other type of dementia, or significant neurologic diseases such as Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head trauma or normal pressure hydrocephalus;

- Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or longer if evidence of reactive depression or temporary mood disturbances) or clinically significant psychopathology, (e.g., psychosis and schizophrenia); if hospitalized in past year, can be rescreened in 6 months; or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures.

- Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), or other severe medical conditions;

- History of atrial fibrillation and evidence on ECG with any of the following: active symptoms of persistent palpitation, dizziness, history of syncope, chest pain, dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea within the past 6 months; resting heart rate of < 30 or > 110 bpm; taking class I or III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in lowering blood pressure.

- Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than 110 mmHg, may be rescreened in 1 week.

- Orthostatic hypotension, defined as the third standing SBP < 100mmHg, may be rescreened after 2 weeks;

- History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis or polymyalgia rheumatica;

- Significant history of alcoholism or drug abuse within the last five years;

- Uncontrolled diabetes mellitus, defined as hemoglobin A1C > 6.5%, or requiring insulin treatment;

- Clinically diagnosed and untreated sleep apnea;

- Regularly smoking cigarettes within the past year;

- Pacemaker or other medical device of metal that precludes performing MRI;

- Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal or surgically sterile to be considered not childbearing potential);

- Participant enrolled in another investigational drug or device study, either currently or within the past 2 months;

- Severe obesity with BMI > 40 ; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance;

- Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix "-sartan"; allergy to amlodipine;

- Abnormal screening laboratory tests (e.g., liver ALT and AST > 3 x ULN, GFR < 30 or Hct < 28%); may be rescreened after 2 weeks or longer;

- A medical condition likely to limit survival to less than 3 years;

- Participant has any condition(s) judged by the study investigator to be medically inappropriate, risky or likely to cause poor study compliance. For example: