Public Health.

Area of Science:

• Neurology
• Gerontology
• Public Health

Background:

• Amyloid-targeting therapies for Alzheimer's disease (AD) are emerging but their population-level impact and eligibility remain unclear.
• Accurate estimation requires sophisticated modeling of patient populations and treatment criteria.

Purpose of the Study:

• To adapt the MISCAN-Dementia microsimulation model for estimating the eligible population and population-wide impact of amyloid-targeting therapies.
• To refine the model with specific parameters for amyloid positivity in mild cognitive impairment (MCI) and mild AD dementia stages.

Main Methods:

• Utilized the established MISCAN-Dementia microsimulation model.
• Incorporated age- and dementia-stage specific parameters for amyloid positivity.
• Validated MCI stage with external data (Mayo Clinic Study of Aging) and added comorbidities restricting therapy use.

Main Results:

• Methodological challenges in validating MCI incidence and prevalence due to heterogeneous data and diagnostic variability were addressed.
• External validation using high-quality population-based data was performed.
• Adaptations for amyloid status and comorbidities are ongoing within the MISCAN-Dementia model.

Conclusions:

• The MISCAN-Dementia model is being adapted to provide population-wide impact estimates for amyloid-targeting therapies.
• Model modifications and methodological considerations are presented, alongside initial eligible population estimates.
• Future steps include estimating population-wide benefits and harms of these therapies.