Disease progression model using the integrated Alzheimer's Disease Rating Scale

Area of Science:

• Neurology
• Clinical Trials
• Biostatistics

Background:

• Alzheimer's disease (AD) dementia progression is complex.
• Accurate modeling is crucial for clinical trial design and interpretation.

Purpose of the Study:

• Develop a disease progression model for AD dementia using the integrated Alzheimer's Disease Rating Scale (iADRS).
• Characterize factors influencing iADRS scores and disease progression rate.
• Provide a tool to aid in optimizing future AD clinical trials.

Main Methods:

• Developed a disease progression model using NONMEM (version 7.4.2).
• Utilized data from 3483 placebo participants across six AD trials.
• Examined participants with mild cognitive impairment, and mild to moderate AD dementia.

Main Results:

• Baseline iADRS scores were influenced by AD medication use, EXPEDITION2 enrollment, age, and Mini-Mental State Examination (MMSE) scores.
• Disease progression rate increased with disease stage and was affected by AD medication use, age, and baseline MMSE.
• Apolipoprotein E ε4 carrier status did not impact baseline iADRS or progression.

Conclusions:

• The developed model accurately describes the iADRS time course across the AD severity spectrum.
• This model can enhance clinical trial design and treatment effect interpretation in AD research.
• Linear regression allows iADRS score calculation from MMSE scores.