Structural MRI changes detectable up to ten years before clinical Alzheimer's disease

Manuela Tondelli, Gordon K. Wilcock, Paolo Nichelli, Celeste A. de Jager, Mark Jenkinson, Giovanna Zamboni

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186 Citations (Scopus)


Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.

Original languageEnglish
Pages (from-to)825.e25-825.e36
JournalNeurobiology of Aging
Issue number4
Publication statusPublished or Issued - Apr 2012
Externally publishedYes


  • Alzheimer's disease (AD)
  • Mild cognitive impairment (MCI)
  • Preclinical AD
  • Structural MRI
  • Voxel-based morphometry (VBM)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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