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

This study is intended to investigate the safety of candesartan, a blood pressure medication, in non-hypertensive individuals who have mild cognitive impairment (MCI) due to Alzheimer's disease and its effect on disease biomarkers.

This is a double-blind placebo-control randomized clinical trial that compares candesartan to placebo in individuals with mild cognitive impairment (MCI) who also have positive Alzheimer's Disease (AD) biomarkers. The investigators will assess if blocking the effect of Ang II using angiotensin receptor blockers (ARBs) is safe in non hypertensive MCI individuals and whether the use of candesartan will be associated with changes in cerebrospinal fluid disease biomarkers.

Eligibility Criteria:
Inclusion Criteria:

* Mild Cognitive Impairment, defined by:

  * Subjective memory concern
  * Abnormal memory function documented using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): \[\<11 for 16 or more years of education; \<9 for 8-15 years of education; \<6 for \<7 years of education\]
  * Montreal Cognitive Assessment (MoCA) \< 26
  * Clinical Dementia Rating scale /Memory sum Box score=0.5
  * General functional performance sufficiently preserved (Functional Assessment Questionnaire\<9)
* Amyloid positivity determined by measuring the amyloid content in the brain. This can be 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 of antihypertensive medications other than ACEI or ARBs for other indications is allowed)
* Current diagnosis of hypertension or current use of antihypertensive medication that is 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 would affect the safety of the subject or scientific integrity of the study
* Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath
* History of stroke in the past 3 years
* Inability to have MRI (eg metal implants or cardiac pacemaker) with an exception for those who cannot have an MRI, if all other parts of the study are obtained successfully they may still be enrolled in the study, or cognitive assessment or inability to assess amyloid positivity (no lumbar puncture and no amyloid scan)
* History of increased intracranial pressure (ICP) or bleeding diathesis (from disease states or from use of anticoagulants such as warfarin, heparin and related products, rivaroxaban or Xarelto, apixaban or Eliquis, edoxaban or Savaysa, dabigatran or Pradaxa)
* 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 on their behalf will be required, otherwise they will be excluded
* Current use of Lithium, as candesartan may increase lithium concentration to toxic levels