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Structural correlates of early and late onset Alzheimer’s disease: voxel based morphometric study
  1. G B Frisoni1,2,
  2. C Testa1,3,
  3. F Sabattoli1,
  4. A Beltramello4,
  5. H Soininen5,
  6. M P Laakso5,6
  1. 1Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF, Brescia, Italy
  2. 2AFaR – Associazione Fatebenefratelli per la Ricerca, Rome, Italy
  3. 3Machine Vision Laboratory, Department of Mathematics and Computer Science, University of Udine, Udine, Italy
  4. 4Service of Neuroradiology, Ospedale Maggiore, Verona, Italy
  5. 5Department of Neurology, Kuopio University Hospital, Kuopio, Finland
  6. 6Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
  1. Correspondence to:
 Dr G B Frisoni
 Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF, via Pilastroni 4, I-25123 Brescia, Italy;;


Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer’s disease.

Methods: We studied nine patients with early onset (age ⩽65 years), nine with late onset (age >65) Alzheimer’s disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age ⩽65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic.

Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype.

Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer’s neuropathology.

  • ApoE, apolipoprotein E
  • CDR, clinical dementia rating (scale)
  • CT, computed tomography
  • EO/LOAD, early onset/late onset Alzheimer’s disease
  • MRI, magnetic resonance imaging
  • PET, positron emission tomography
  • SPECT, single photon emission computed tomography
  • VBM, voxel based morphometry
  • age at onset
  • Alzheimer’s disease
  • voxel based morphometry

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  • The study was supported by the Research Council for Health of the Academy of Finland, EVO grants 5772720 from the Kuopio University Hospital, and Maire Taponen Foundation.

  • Competing interests: none declared