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Cerebral Cortex Advance Access published online on November 10, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh200
© 2004 by Oxford University Press
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Article

Focal Decline of Cortical Thickness in Alzheimer's Disease Identified by Computational Neuroanatomy

Jason P. Lerch 1, Jens C. Pruessner 2, Alex Zijdenbos 1, Harald Hampel 3, Stefan J. Teipel 3, and Alan C. Evans 1*

1 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
2 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Alzheimer Memorial Center, Dementia Research Section and Memory Clinic, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany
3 Alzheimer Memorial Center, Dementia Research Section and Memory Clinic, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany

* To whom correspondence should be addressed.
Alan C. Evans, E-mail: alan{at}bic.mni.mcgill.ca


  Abstract

Alzheimer's disease (AD) is characterized by a heterogeneous distribution of pathological changes throughout the brain. Magnetic resonance imaging can be used to investigate the regional distribution of cortical atrophy in AD in vivo. One marker for the disease-specific atrophy is the thickness of the cortical mantle across the brain, obtained with automated 3-D image processing. Here, we present data from 36 subjects (17 controls and, 19 patients diagnosed as probable AD) investigated for cortical thickness across the entire brain. We show significant cortical thickness decline in AD in temporal, orbitofrontal and parietal regions, with the most pronounced changes occurring in the allocortical region of the medial temporal lobes, outlining the parahippocampal gyrus, and representing a loss of >1.25 millimeters of cortical thickness. Moreover, focal cortical areas decline with progression of the disease as measured by time from baseline scan as well as the Mini-Mental State Exam. The results demonstrate the ability of this method to detect changes in cortical thickness in AD, across the entire brain, without need of prior anatomical definitions. The regional distribution of changes reported here is consistent with independent findings on the distribution of neuropathological alterations in AD. Using cortical thickness, moreover, we provide a direct quantitative index of atrophy in the disease.

Keywords: Alzheimer's disease; automated 3-D image analysis; cortical thickness; MRI; neuroinformatics; neuropathology.
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