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

Objective: To investigate the relationship between in vivo brain amyloid-beta (A beta) burden, measured by C-11-labeled Pittsburgh Compound B (C-11-PiB) retention, and age-at-onset in patients with Alzheimer disease (AD). Design: Cross-sectional study. Setting: University Dementia Clinic. Participants: 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 epsilon 4 allele number. Intervention: C-11-PiB positron emission tomography scans. Measurements: Both region of interest and voxel-based analyses were performed to compare C-11-PiB retention between EOAD and LOAD groups, and to test linear relationship between age-at-onset and C-11-PiB retention. Results: Both region of interest (ROI) and voxel-based analyses revealed that EOAD patients had significantly higher C-11-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-11-PiB retention was significant in LOAD but not in EOAD. Conclusions: Our finding of a heavier A beta 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 A beta burden is possibly associated with aging-related decrease of brain or cognitive reserve and with aging-related increase of brain vulnerability. (Am J Geriatr Psychiatry 2011; 19:627-634)