Risk Reduction for Alzheimer's Disease

Exclusion Criteria

• •1. 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.
• •2. 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.
• •3. 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.
• •4. 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.
• •5. 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 anti-arrhythmic drugs including flecanide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in exercise and lowering blood pressure.
• •6. Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than 110 mmHg, may be rescreened in 1 week.
• •7. Orthostatic hypotension, defined as the third standing SBP \< 100mmHg, may be rescreened after 2 weeks.
• •8. History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, or polymyalgia rheumatic.
• •9. Significant history of alcoholism or drug abuse within the last five years.
• •10. Uncontrolled diabetes mellitus, defined as hemoglobin A1C \> 7.5%, or requiring insulin treatment.
• •11. Regularly smoking cigarette within the past year.
• •12. Women with a potential for pregnancy, lactation/child bearing (2 year post- menopausal or surgically sterile to be considered not child bearing potential).
• •13. Participant enrolled in another investigational drug or device study, either currently or within the past 2 months.
• •14. Severe obesity with BMI ≥ 45; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance.
• •15. Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix "-sartan".
• •16. Allergy to other study drugs or their ingredients; for example, clinical history or self-reported allergy or intolerance to atorvastatin.
• •17. Abnormal screening laboratory tests (e.g., liver ALT and AST \> 3 x ULN, CK \> 3 x ULN, GFR \< 30 or Hct \< 28%); may be rescreened after 2 weeks or longer.
• •18. A medical condition likely to limit survival to less than 3 years.
• •19. Participant has any condition(s) judged by the study investigator to be medically inappropriate, risky or likely to cause poor study compliance. For example:
• •1. Plans to move outside the clinic catchment area in the next 2 years;
• •2. Significant concerns about participation in the study from spouse, significant other, or family members;
• •3. Lack of support from primary health care provider;
• •4. Residence too far from the study clinic site such that transportation is a barrier including persons who require transportation assistance provided by the study clinic funds for screening or randomization visits;