Characterizing Clinical Progression in Cognitively Unimpaired Older Individuals with Brain Amyloid: Results from the A4 Study
ABSTRACT
Researchers studied the sensitivity of Clinical Dementia Rating (CDR) in measuring pre-symptomatic Alzheimer’s disease progression in the A4 study. They examined specific CDR boxes and their changes over time in individuals with brain amyloid.
SETTING
The A4 study took place at 67 sites in Australia, Canada, Japan, and the United States.
PARTICIPANTS
1,147 individuals, ages 65-85, were randomized to receive either placebo (n= 583) or solanezumab (n= 564). They underwent baseline flobetapir PET scans, annual CDR assessments, and cognitive testing every 6 months over 240 weeks.
MEASUREMENTS
Generalized estimating equations and generalized least square models were used to explore the progression rate in CDR measures and individual CDR boxes in both placebo and solanezumab groups. Models were adjusted for various factors including age, education, APOEε4 carrier status, and baseline amyloid levels.
RESULTS
There were no significant differences between the placebo and solanezumab groups in CDR measures. Changes in judgment/problem solving were present at baseline and persisted, while memory and cognitive composite scores quickly predominated. Functional changes in community affairs and home/hobbies were relatively stable, and personal care remained unchanged. Cognitive and functional progression in CDR boxes began at intermediate or advanced amyloid levels, while lower amyloid levels showed little progression.
CONCLUSIONS
The study suggests that specific CDR box score changes, particularly in memory and cognitive composite, may help refine the measurement of expected treatment effects in future Alzheimer’s disease prevention trials.
PMID: 39044489 | DOI: 10.14283/jpad.2024.123
