Relationship of amyloid-β burden with age-at-onset in Alzheimer disease

Am J Geriatr Psychiatry. 2011 Jul;19(7):627-34. doi: 10.1097/JGP.0b013e318202bf3a.

Abstract

Objective: 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).

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 ε4 allele number.

Intervention: C-PiB positron emission tomography scans.

Measurements: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography

Substances

  • Amyloid beta-Peptides