Journal of Neurology

, 256:916 | Cite as

In vivo mapping of incremental cortical atrophy from incipient to overt Alzheimer’s disease

  • Giovanni B. Frisoni
  • Annapaola Prestia
  • Paul E. Rasser
  • Matteo Bonetti
  • Paul M. Thompson
Original Communication


Progressive brain atrophy is believed to be the Alzheimer’s disease (AD) marker with the greatest evidence for validity. Mapping the topography of cortical atrophy throughout the stages of severity may allow the neural networks affected to be identified. Twenty healthy elderly persons (OH, MMSE 29.1 ± 1.0), 11 patients with incipient AD (iAD, 26.5 ± 2.0), 15 with mild AD (miAD, 23.5 ± 2.2), and 15 with moderate AD (moAD, 16.5 ± 2.0) underwent 3D magnetic resonance. Cortical pattern matching analysis was performed and maps of percent differences in gray matter distribution were computed between the following groups: iAD versus OH, miAD versus iAD, and moAD versus miAD. Compared to OH, iAD patients exhibited a mean cortical gray matter loss of 9–20% in areas encompassing the polysynaptic hippocampal pathway (posterior cingulate/retrosplenial and medial temporal cortex) and subgenual/orbitofrontal cortices, and a less widespread loss of 5–11% in other neocortical areas. Compared to iAD, miAD featured widespread mean gray matter loss of 14–19% in areas encompassing the direct hippocampal pathway (temporal pole, temporoparietal association cortex, and dorsal prefrontal cortex), sensorimotor, and visual cortex, with a less marked loss (7–9%) in the polysynaptic pathway areas. Compared to miAD, only atrophy in the primary sensorimotor cortex was still relatively marked in moAD, with a mean gray matter loss of 10–11%; the loss in other regions was generally below 10%. These findings suggest that the polysynaptic hippocampal pathway is affected in iAD, the direct pathway and sensorimotor and visual networks are affected in moAD, and the sensorimotor network is affected in moAD.


Alzheimer’s disease Cortical pattern matching Brain atrophy Mild cognitive impairment (MCI) Volumetric MRI 



We wish to thank Francesca Sabattoli for help in the inter-rater reliability of cortical pattern matching, and Michela Pievani for continuous technical and logistic support.

Conflict of interest statement

The authors report no conflicts of interest.

Supplementary material

415_2009_5040_MOESM1_ESM.doc (818 kb)
Supplementary figures (DOC 818 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Giovanni B. Frisoni
    • 1
    • 2
  • Annapaola Prestia
    • 1
  • Paul E. Rasser
    • 3
    • 4
  • Matteo Bonetti
    • 5
  • Paul M. Thompson
    • 6
  1. 1.Laboratory of Epidemiology Neuroimaging and TelemedicineIRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer’s and Mental DiseasesBresciaItaly
  2. 2.Psychogeriatric WardIRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer’s and Mental DiseasesBresciaItaly
  3. 3.Schizophrenia Research InstituteSydneyAustralia
  4. 4.Priority Centre for Brain and Mental Health Research, School of Design, Communication and ITUniversity of NewcastleNewcastleAustralia
  5. 5.Service of NeuroradiologyIstituto Clinico Città di BresciaBresciaItaly
  6. 6.Laboratory of Neuro ImagingUCLA School of MedicineLos AngelesUSA

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