Candesartan's Effects on Alzheimer's Disease And Related Biomarkers

Inclusion Criteria:

• Mild Cognitive Impairment, defined by:
• Subjective memory concern
• Abnormal memory function documented using the Logical Memory subscale (DelayedParagraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (themaximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 yearsof education; <6 for <7 years of education]
• Montreal Cognitive Assessment (MoCA) < 26
• Clinical Dementia Rating scale /Memory sum Box score=0.5
• General functional performance sufficiently preserved (Functional AssessmentQuestionnaire<9)
• Amyloid positivity determined by measuring the amyloid content in the brain. This canbe determined by either cerebrospinal fluid (CSF) amyloid level or an amyloid scan (PIB-PET)

Exclusion Criteria:

• Intolerance to ARBs
• Current use of ARBs, angiotensin-converting enzyme inhibitors (ACEIs) (use ofantihypertensive medications other than ACEI or ARBs for other indications is allowed)
• Current diagnosis of hypertension or current use of antihypertensive medication thatis prescribed specifically for hypertensive therapy
• SBP less than 110 or DBP less than 40 mm Hg
• Renal disease (Creatinine >2.0 mg/dl), hyperkalemia (K>5.5 meq/dl),platelets<50,000/μl, or international normalized ratio (INR)>1.9
• Active medical or psychiatric diseases that in the judgment of the investigator wouldaffect the safety of the subject or scientific integrity of the study
• Uncontrolled congestive heart failure reflected by poor exercise tolerance andshortness of breath
• History of stroke in the past 3 years
• Inability to have MRI (eg metal implants or cardiac pacemaker) with an exception forthose who cannot have an MRI, if all other parts of the study are obtainedsuccessfully they may still be enrolled in the study, or cognitive assessment orinability to assess amyloid positivity (no lumbar puncture and no amyloid scan)
• History of increased intracranial pressure (ICP) or bleeding diathesis (from diseasestates or from use of anticoagulants such as warfarin, heparin and related products,rivaroxaban or Xarelto, apixaban or Eliquis, edoxaban or Savaysa, dabigatran orPradaxa)
• Women of childbearing potential (non-menopausal)
• In those who are unable to demonstrate that they understood the details of the study (ie lack of decisional-capacity to consent), a study partner/surrogate who can sign ontheir behalf will be required, otherwise they will be excluded
• Current use of Lithium, as candesartan may increase lithium concentration to toxiclevels