Rapamycin - Effects on Alzheimer's and Cognitive Health

The study will consist of a screening/baseline period of up to 90 days pre-study drug, with a 12-month (+3 day) treatment period with rapamycin, followed by a post-treatment assessment completed within 14 days of the final study drug dose, and a final assessment conducted 6-months (+14 days) after the final study drug dose. The study duration is not expected to exceed 90 weeks for participants.

Inclusion criteria

• Both genders and all ethnic groups
• Ages 55 to 89 years
• Diagnosis of MCI or AD (Mini Mental Status Examination (MMSE): 18-30; Clinical Dementia Rating Scale (CDR) = 0.5 - 1; California Verbal Learning Test III (CVLT-III) Delayed Recall ≤16% based on age-adjusted norms, clinician approval)
• Amyloid positivity based on Amyloid PET Imaging
• Labs: Normal blood cell counts without clinically significant excursions; normal liver and renal function; and glucose control (HbA1c < 6.5%). Fasting lipid panel and prothrombin time/prothrombin time test/international normalized ration (PT/PTT/INR) within normal limits
• A legally authorized representative (LAR) designated to sign informed consent (if necessary) must attend the Screening visit and accompany the participant to all remaining visits to provide reported outcomes
• Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed

Exclusion criteria

• Diabetes (HBA1c≥6.5% or antidiabetic medications)
• History of skin ulcers or poor wound healing
• Current tobacco or illicit drug use or alcohol abuse
• Use of anti-platelet or anti-coagulant medications other than aspirin
• Current medications that affect cytochrome 450 3A4 (CYP3A4)
• Immunosuppressant therapy within the last year
• Chemotherapy or radiation treatment within the last year
• Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
• Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)
• Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
• Chronic heart failure
• Pregnancy or lactation
• Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
• Significant neurological conditions other than AD or MCI
• Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)
• Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
• History of, or MRI, or CT positive for, any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindications to lumbar puncture
• Organ transplant recipients