Disentangling the normal aging from the pathological Alzheimer's disease progression on structural MR images

Abstract : Background. The morphology of the brain observed in patients affected by Alzheimer's disease (AD) is the contribution of different biological processes such as the normal aging and the AD-specific pathological matter loss. Being able to differentiate these complementary biological factors is fundamental in order to isolate and quantify the pathological AD-related structural changes, especially at the earliest phase of the disease, at prodromal and preclinical stages. Methods. We chose the ADNI baseline structural MRIs for 37 healthy subjects positive to the CSF Ab42 (Ab+), 86 patients with mild cognitive impairment (MCI) which subsequently converted to AD, 110 stable MCI, and 134 AD patients. For each subject, a "virtual aging" component was defined as the closest point with respect to the longitudinal deformation modeled for the healthy aging of a group of 63 normal subjects negative to the CSF Ab42 [1]. Once removed the aging component, the remaining specific morphological changes were analyzed group-wise, in order to characterize the atrophy patterns at the different clinical stages, and to test their predictive power in encoding the pathological disease progression. Results. Even though the considered groups did not significantly differ for age, the estimated virtual ages increased as the clinical condition get worse, and were significantly higher for the MCI stable, converters, and AD groups when compared to the healthy Aβ- (p<0.05, standard two sample t-test). After removing the healthy component, the morphological changes specific for the healthy Aβ+ were mild, while the changes specific for the MCI converters were more pronounced and mapped to frontal lobes, ventricles, temporal poles, entorhinal cortex and hippocampi. The same pattern, although slightly more pronounced, was appreciable for the AD patients. The stable MCIs showed a milder deformation pattern, mapping essentially to the ventricles and temporal poles. The predictive power of the specific component was 91% sensitivity and 84 % specificity for the discrimination AD vs healthy, and 67% sensitivity and 63 % specificity for the discrimination MCI stable vs MCI converters. Conclusion. We provided a rich description of the anatomical changes observed across the AD time span: normal aging, normal aging at risk, conversion to MCI and latest AD stages. More advanced AD stages were associated to both "virtually older" brains, and to increased specific morphological changes that were not related to the normal aging. Importantly, the specific changes provided a good identification of the pathological AD atrophy. These results provide new insights that can lead to new understandings of the AD dynamics, and to novel techniques for the modeling and the early detection of the disease.
Type de document :
Communication dans un congrès
5th Clinical Trials in Alzheimer's Disease (CTAD'12), Oct 2012, Monte Carlo, Monaco. 2012
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Contributeur : Project-Team Asclepios <>
Soumis le : mardi 16 avril 2013 - 11:18:50
Dernière modification le : jeudi 11 janvier 2018 - 16:42:58


  • HAL Id : hal-00813844, version 1



Marco Lorenzi, Nicholas Ayache, Xavier Pennec, Giovanni B. Frisoni, (adni) For The Alzheimer'S Disease Neuroimaging Initiative. Disentangling the normal aging from the pathological Alzheimer's disease progression on structural MR images. 5th Clinical Trials in Alzheimer's Disease (CTAD'12), Oct 2012, Monte Carlo, Monaco. 2012. 〈hal-00813844〉



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