Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography

Inclusion criteria

• Clinical diagnosis of mild cognitive impairment (MCI), or dementia of Alzheimer's type
• Amyloid positivity established with either amyloid positron emission tomography or cerebrospinal fluid analysis.
• For subjects with dementia, the disease should be in an early stage, operationalized as:

• Stage 4 (Mild dementia) or lower, according to the National Institute on Aging - Alzheimer's Association 2018 clinical staging criteria, AND
• Clinical Dementia Rating Scale (CDR) global score of 1 or lower, AND
• Montreal Cognitive Assessment (MoCA) score of ≥ 18 OR Rey Auditory Verbal Learning Test (RAVLT) >4 words after 30 minutes
• Capable of giving, and has the capacity to give informed consent
• Availability of a responsible study partner who can accompany the subject to all planned visits
• Male or female between 50 and 80 years
• Normal or clinically acceptable medical history, physical examination, and vital signs

Exclusion criteria

• History of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes).
• Central nervous system infarct, infection, or focal lesions of clinical significance on MRI scans.
• Fulfills any contraindication for the use of sirolimus as per the summary of product characteristics, including but not restricted to:

• Current or planned medication with a strong inhibitor of CYP3A4 or P-gp
• Current or planned medication with a strong inducer of CYP3A4 or P-gp
• Other current medications with known serious interaction risks with sirolimus
• Known allergy or hypersensitivity to sirolimus
• Significant obesity
• Untreated and clinically significant hyperlipidemia
• Treatment with immunosuppressive medications within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted), or chemotherapeutic agents for malignancy within the last 3 years
• Major surgery within 3 months prior to the planned start of sirolimus treatment, OR has major surgery planned during the period of the trial.
• Use of experimental medications for Alzheimer's or any other investigational medication or device within 60 days. Participants who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial