Accelerating cortical thinning: unique to dementia or universal in aging?

Cereb Cortex. 2014 Apr;24(4):919-34. doi: 10.1093/cercor/bhs379. Epub 2012 Dec 12.


Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ(1-42) levels, and apolipoprotein ε4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.

Keywords: Alzheimer's disease; aging; atrophy; cortical thickness; magnetic resonance imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging*
  • Alzheimer Disease / complications
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Cerebral Cortex / pathology*
  • Cross-Sectional Studies
  • Dementia / cerebrospinal fluid
  • Dementia / etiology
  • Dementia / pathology*
  • Disease Progression
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Young Adult


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)