Structural Brain Alterations before Mild Cognitive Impairment in ADNI: Validation of Volume Loss in a Predefined Antero-Temporal Region

Issue title: Predictive Biomarkers for Alzheimer's Disease using State-of-the-Art Brain Imaging Techniques

Guest editors: Pravat K. Mandal

Article type: Research Article

Authors: Smith, Charles D.^{a; b; c; d; *} | Andersen, Anders H.^{b; d} | Gold, Brian T.^{b; c; d} | For the Alzheimer's Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [b] Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [c] Sanders-Brown Center on Aging Alzheimer's Disease Center, University of Kentucky, Lexington, KY, USA | [d] Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA

Correspondence: [*] Correspondence to: Charles D. Smith, Room 62, MRISC (Davis-Mills) Bldg., UK Medical Center, 800 Rose St., Lexington, KY 40536-0098, USA. Tel.: +1 859 323 1113; Fax: +1 859 323 1068; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wpcontent/uploads/how to apply/ADNI_Acknowledgement_List.pdf.

Abstract: Volume losses in the medial temporal lobe, posterior cingulated, and orbitofrontal region have been observed in Alzheimer's disease (AD). Smaller reductions in similar regions have also been reported in amnestic mild cognitive impairment (aMCI), a canonical precursor to AD. We previously demonstrated that volume loss in bilateral anteromedial temporal lobe is present at baseline in longitudinally followed normal subjects who later developed MCI or AD. In this study we compared grey matter volumes within this predefined anteromedial temporal region (AMTR) at baseline between: 1) normal subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who subsequently developed cognitive complaints as reflected in a CDR memory box score of 0.5; and 2) normal subjects who remained normal over a median of 48 months of follow-up (CDR sum of boxes 0). We found significantly decreased volume within AMTR in the ADNI memory complainers. To relate AMTR results to those from conventional anatomy, we demonstrate that volumes extracted with the ICBM amygdala region had the best correspondence with AMTR volumes. In contrast, regions that have demonstrated volume loss in frank MCI and AD in ADNI, e.g., the posterior cingulate, did not show volume loss. These findings provide independent confirmation that volume changes preceding MCI occur in AMTR, a region of overlap between amygdala and anterior hippocampus.

Keywords: Alzheimer's disease neuroimaging initiative, Alzheimer's disease risk, amygdala, brain aging, hippocampus, longitudinal studies, magnetic resonance imaging, medial temporal lobe, structural neuroimaging, voxel-based morphometry

DOI: 10.3233/JAD-2012-120157

Journal: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S49-S58, 2012