Relationship of Amyloid-Beta Burden With Age-At-Onset in Alzheimer Disease

Abstract

To investigate the relationship between in vivo brain amyloid-beta (Aβ) burden, measured by C-labeled Pittsburgh Compound B (C-PiB) retention, and age-at-onset in patients with Alzheimer disease (AD). Cross-sectional study. University Dementia Clinic. Twenty-two AD patients including 11 early-onset AD (EOAD: onset <65 years) and 11 late-onset AD (LOAD: onset ≥65years) cases with matched dementia severity, duration of illness, and apolipoprotein E ε4 allele number. C-PiB positron emission tomography scans. Both region of interest and voxel-based analyses were performed to compare C-PiB retention between EOAD and LOAD groups, and to test linear relationship between age-at-onset and C-PiB retention. Both region of interest (ROI) and voxel-based analyses revealed that EOAD patients had significantly higher C-PIB retentions than LOAD patients in diffuse brain regions including frontal, lateral parietal, lateral temporal, and occipital cortex, and basal ganglia. Subgroup analyses showed that negative correlation between age-at-onset and C-PiB retention was significant in LOAD but not in EOAD. Our finding of a heavier Aβ burden in the brain of living EOAD patients than LOAD patients is in agreement with those from postmortem studies. The inverse relationship between age-at-onset and Aβ burden is possibly associated with aging-related decrease of brain or cognitive reserve and with aging-related increase of brain vulnerability.