Staging Alzheimer's disease progression with multimodality neuroimaging

Michael Ewers, Giovanni B. Frisoni, Stefan J. Teipel, Lea T. Grinberg, Edson Amaro, Helmut Heinsen, Paul M. Thompson, Harald Hampel

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations


Rapid developments in medical neuroimaging have made it possible to reconstruct the trajectory of Alzheimer's disease (AD) as it spreads through the living brain. The current review focuses on the progressive signature of brain changes throughout the different stages of AD. We integrate recent findings on changes in cortical gray matter volume, white matter fiber tracts, neuropathological alterations, and brain metabolism assessed with molecular positron emission tomography (PET). Neurofibrillary tangles accumulate first in transentorhinal and cholinergic brain areas, and 4-D maps of cortical volume changes show early progressive temporo-parietal cortical thinning. Findings from diffusion tensor imaging (DTI) for assessment fiber tract integrity show cortical disconnection in corresponding brain networks. Importantly, the developmental trajectory of brain changes is not uniform and may be modulated by several factors such as onset of disease mechanisms, risk-associated and protective genes, converging comorbidity, and individual brain reserve. There is a general agreement between in vivo brain maps of cortical atrophy and amyloid pathology assessed through PET, reminiscent of post mortem histopathology studies that paved the way in the staging of AD. The association between in vivo and post mortem findings will clarify the temporal dynamics of pathophysiological alterations in the development of preclinical AD. This will be important in designing effective treatments that target specific underlying disease AD mechanisms.

Original languageEnglish
Pages (from-to)535-546
Number of pages12
JournalProgress in Neurobiology
Issue number4
StatePublished - Dec 2011
Externally publishedYes


  • AD
  • ADNI
  • Alzheimer's disease
  • Biological activity
  • Biological markers
  • CSF
  • Classification
  • Clinical trials
  • Computational
  • DBM
  • DTI
  • Diagnosis
  • Drug development
  • Early detection
  • FDA
  • FMRI
  • MCI
  • MRI
  • Mild cognitive impairment
  • Multimodal
  • Neuroanatomy
  • Neuroimaging
  • Neuropathology
  • Pre-clinical
  • Pre-dementia
  • Pre-symptomatic
  • Prediction
  • Regulatory authorities
  • Staging
  • Tractography
  • VBM


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