Table 1 Eligibility criteria

Inclusion criteria

 1. Age: 55–80 years.

 2. Has an available “study partner” who can accompany the participant to planned visits.

 3. Has a clinical diagnosis of MCI (mild cognitive impairment) or dementia of the Alzheimer's type, and:

   ◦ At inclusion, the participant meets the criteria for “Alzheimer’s clinical syndrome”, MCI, or mild dementia of the Alzheimer's type, according to the NIA-AA (National Institute of Aging-Alzheimer's Association) 2018 criteria [42].

   ◦ At inclusion, the participant is amyloid positive, established with either amyloid PET imaging, or a CSF beta amyloid 1–42 assay, or a CSF beta amyloid 1–42/ beta amyloid 1–40 assay.

     3.1 For participants with dementia, the disease should be in an early stage, operationalized as:

       ◦ Having stage 4 mild dementia or lower, according to the NIA-AA 2018 clinical staging criteria [42].

       ◦ Having a clinical Dementia Rating Scale (CDR) global score of 1 or lower.

       ◦ Having a Montreal Cognitive Assessment (MoCA) score of ≥ 18 or a Rey Auditory Verbal Learning Test (RAVLT) > 4 words after 30 min.

     3.2 For participants with a diagnosis of MCI, a cognitive deficit with > -1SD in at least one of the following cognitive tests: Wechsler Adult Intelligence Scale subtest to assess processing speed/attention, Rey Auditory Verbal Learning Test (learning and delayed recall), or Rey Complex Figure Test.

 4. Is proficient in the Swedish language.

 5. Has a normal or clinically acceptable medical history, physical examination, and vital signs.

 6. For female participants, the participant has no childbearing potential, meaning that she is surgically sterile or post-menopausal, or has a negative pregnancy test following a menstrual period AND uses an acceptable effective contraceptive measure, which must be continued for at least 12 weeks after stopping the study drug.

Exclusion criteria

 1. Has a history of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes).

 2. Has a history of a major neurological disorder, central nervous system infarct, infection or focal lesions of clinical significance on MRI scans.

 3. There is evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, including schizophrenia or other psychotic disorder, or bipolar disorder.

 4. Fulfills any contraindication for the use of rapamycin, 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 rapamycin.

   ◦ Known allergy or hypersensitivity to rapamycin.

 5. Has significant obesity, as per the investigator's judgement.

 6. Has untreated hyperlipidemia that is clinically significant, as per the investigator's judgement.

 7. Has undergone treatment with immunosuppressive medications within the last 90 days, or treatment with chemotherapeutic agents for malignancy within the last 3 years.

 8. Has had major surgery within 3 months prior to the planned start of rapamycin treatment, or has major surgery planned during the trial period.

 9. Has used experimental medications for AD or any other investigational medication or device within the last 60 days of inclusion.

   ◦ Participants who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial.