Brain Advance Access originally published online on May 12, 2009
Brain 2009 132(8):2036-2047; doi:10.1093/brain/awp105
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Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve
1 Inserm; Imagerie cérébrale et handicaps neurologiques UMR 825; F-31059 Toulouse, France 2 Université de Toulouse; UPS; Imagerie cérébrale et handicaps neurologiques UMR 825; CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France 3 Centre Hospitalier Universitaire de Toulouse; Pôle Neurosciences; CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France 4 CNRS; Institut de Mathématiques de Toulouse UMR 5219; Université Paul Sabatier; F-31000 Toulouse, France 5 Université de Toulouse; UPS; Institut de Mathématiques de Toulouse UMR 5219; 118 route de Narbonne, F-31062 Toulouse Cedex 9, France
Correspondence to: Olivier Querbes or Pierre Celsis, INSERM U 825, Hôpital Purpan, Place du Docteur Baylac, Pavillon Riser, 31059 Toulouse, France E-mail: olivier.querbes{at}inserm.fr or pierre.celsis{at}inserm.fr
Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.
Key Words: Early Alzheimer's disease; individual diagnosis; mild cognitive impairment; magnetic resonance imaging (MRI); cognitive reserve
Abbreviations: aD, anatomically demented; ADAS-Cog, Alzheimer's disease Assessment Scale score; ADNI, Alzheimer's disease Neuroimaging Initiative; aH, anatomically healthy; aMCI, amnestic Mild Cognitive Impairment; HC, Healthy Control; MMSE, Mini Mental State Examination; MRI, Magnetic Resonance Imaging; NTI, Normalized Thickness Index; pMCI, progressive amnestic Mild Cognitive Impairment; ROC, Receiver Operating Curve; sMCI, stable amnestic Mild Cognitive Impairment
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Received December 19, 2008. Revised March 3, 2009. Accepted March 23, 2009.
*Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or the writing of this report. ADNI investigators include (complete listing available at www.loni.ucla.edu\ADNI\Collaboration\ADNI\Manuscript\Citations.pdf).