Longitudinal Trajectories of the Cognitive Function Index in the A4 Study

Area of Science:

• Neurology
• Neuroscience
• Gerontology

Background:

• The Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Study observed longitudinal consequences of elevated amyloid.
• Previous findings indicated decline on cognitive assessments during the trial.

Purpose of the Study:

• Compare longitudinal patterns of participant and study partner Cognitive Function Index (CFI) separately.
• Examine associations between CFI and the Preclinical Alzheimer Cognitive Composite (PACC) stratified by baseline amyloid tertile.

Main Methods:

• 1,147 participants with elevated amyloid underwent CFI and PACC assessments longitudinally.
• Amyloid levels were categorized into tertiles; participants knew their elevated status but not specific levels.
• Correlations between CFI (participant and study partner) and PACC were analyzed, stratified by baseline amyloid tertile.

Main Results:

• Both participant and study partner CFI indicated worsening cognitive functioning over time, irrespective of treatment.
• The association between higher CFI and worse PACC strengthened longitudinally.
• Study partner CFI showed a significantly higher correlation with PACC than participant CFI, particularly in the highest amyloid tertile.

Conclusions:

• Participant and study partner reports capture subtle cognitive changes in preclinical Alzheimer's Disease (AD).
• Study partner reports align most closely with cognitive decline, especially in individuals with high amyloid burden.