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Welcome to the Dickerson Lab: Cortical signature of Alzheimer's disease

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The study of the so-called "cortical signature" of Alzheimer's disease has been and continues to be a major series of projects in the laboratory. Akram Bakkour has led our "AD signature" project team, which has involved a multidisciplinary and multi-institutional team of neurologists, psychiatrists, psychologists, imaging scientists, and others. We believe that the identification, using quantitative computational MRI data analytic methods, of a consistent set of cortical regions that undergo atrophy early in the course of mild Alzheimer's disease will provide both novel scientific insights into the disease and also the potential for earlier more specific identification of individuals who harbor these changes in brain anatomy. We hope that this will ultimately be useful to assist in the identification of groups of individuals for clinical trials and for monitoring the effects of treatments.

From a scientific perspective, this approach is novel in that it "let's the disease tell us" where it affects the cerebral cortex (based on a whole-cortex exploratory analysis comparing patients with AD to controls) and uses this spatial pattern or "disease signature" as a localizer for future measurements. This "disease localizer" approach draws on concepts from functional neuroimaging, in which, for example, data from a group of subjects is to determine where the performance of a particular task activates the brain. This information is then used to specifically interrogate those regions in future studies. The disease localizer approach draws on this paradigm to investigate the spatial pattern of neurodegenerative disease effects, realizing that these patterns may not respect traditional anatomic boundaries as they are typically defined. This localizer can then be used on a "hypothesis-testing" approach to attempt to identify AD-related cortical atrophy in other groups of AD patients or in patients with milder or absent symptoms.

Presentations have taken place about the cortical signature of Alzheimer's disease at a variety of local, regional, national, and international meetings since 2006.

The first paper was published in July 2008. Click here to read it. The final version was featured as the cover article in the March 2009 issue of Cerebral Cortex. Click here for an image of the cover.

The figure below shows the magnitude of cortical thinning in Alzheimer's disease (AD) in millimeters, derived from pooled analysis of 4 samples of participants. Map shows parameter estimate of amount of thinning across cerebral cortex from general linear model analysis of 267 participants, showing areas where cortex is at least 0.15 mm thinner in AD group than age-matched control group. Color scale shows magnitude of thinning from 0.15 mm (red) through 0.2 mm (yellow) in AD compared with controls.

The initial paper describing the cortical signature of AD was selected as a Faculty of 1000 Medicine paper, which is a web-based peer recognition system that identifies and evaluates the most important articles published in medicine. Read more about it here.

AD signature
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Last modified 2008-07-09 16:34