Rapamycin Treatment For Alzheimer’s Disease And Related Dementias: A Pilot Phase 1 Clinical Trial

Research Summary

An open-label, single-site phase 1 pilot trial asking two questions: does low-dose rapamycin reach the central nervous system in people with mild cognitive impairment or early Alzheimer’s disease, and is an eight-week course tolerable in this group?

Who Or What Was Studied?

Ten adults aged 55-85 (mean age 74, 60% female) with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Every participant received rapamycin 1 mg once daily for eight weeks — there was no placebo group. Average adherence to the study drug was 92%.

What Did The Research Show?

• Rapamycin was not detectable in cerebrospinal fluid before or after treatment, so the trial did not demonstrate that the drug reaches the brain at this dose.
• Twenty adverse events were recorded, sixteen of them mild. Two (urinary urgency and diarrhoea) were judged possibly related to the drug and both resolved. No participant stopped early — all ten completed the trial.
• Systolic blood pressure rose from 127.8 ± 19.0 to 138.2 ± 22.1 mmHg, and haemoglobin A1c, red cell distribution width, MCV and MCH changed slightly. Post-treatment values stayed inside normal clinical ranges.
• Cognitive, functional status and neuropsychiatric test scores did not change significantly over the eight weeks.
• Several cerebrospinal fluid biomarkers (p-tau181, GFAP and NfL, plus Aβ40, Aβ42 and tau fragments in exploratory mass-spectrometry assays) increased from baseline to post-treatment.

Limitations And Interpretation

• Open-label and single-arm with only ten participants: without a placebo group, the biomarker changes cannot be attributed to the drug rather than to disease progression or other factors.
• Eight weeks at 1 mg/day is a low dose and a short exposure; the trial does not show whether higher doses reach the brain or change the course of the disease.
• All participants identified as non-Hispanic white and almost all were college graduates, so the results may not generalise to other populations.
• The blood pressure and biomarker changes are signals to monitor in future trials, not evidence of harm or benefit for people taking rapamycin for other reasons.