Low-Dose Radiotherapy for Alzheimer's Disease

Safety, As Measured By Incidence of Grade 3 or Higher Treatment-Related Adverse Events

The primary endpoint is the proportion of participants who experience at least one treatment-related adverse event of Grade 3 or higher, graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events are assessed continuously and attributed to study treatment (induction plus monthly maintenance low-dose whole-brain radiotherapy) by the investigator. Feasibility is defined by an acceptable rate of Grade 3 or higher treatment-related events: 15% or lower during the Phase I lead-in (first 10 participants) and 20% or lower across the full study population (N=50). Safety is monitored continuously using a Bayesian Beta-Binomial model; the study pauses for Data Safety Monitoring Board review if the posterior probability that the true Grade 3 or higher rate exceeds 20% reaches 0.80 or greater.

Cognitive Preservation, As Measured By Change in Montreal Cognitive Assessment (MoCA) Score From Baseline to Month 12

This secondary endpoint evaluates change in cognitive function measured by the Montreal Cognitive Assessment (MoCA), a 30-point scale on which higher scores indicate better cognition. The measure is the change in MoCA score from baseline to Month 12. The trajectory observed in the study cohort (N=50) is compared against a pooled published historical-control decline rate of 2.5 points per year (Tremont 2022; Julayanont 2014) using a Bayesian longitudinal mixed model for repeated measures with a robust meta-analytic-predictive historical-control prior. The prespecified hypothesis is that participants experience stabilization or a slower rate of MoCA decline than the historical reference. To mitigate practice effects, MoCA is administered on a rotating three-form schedule (Original, 7.1, 7.2), with rater identity and form version locked before prior scores become visible.