Genetic predictors of 12-month change in MRI hippocampal volume in the Alzheimer's Disease Neuroimaging Initiative cohort: Analysis of leading candidates from the AlzGene database

Abstract

not available. IC-S2-03 INTEGRATING MR TECHNIQUES TO STUDY ALZHEIMER’S DISEASE Frederik Barkhof, Alzheimer Center, VU Medical Center, Amsterdam, Netherlands. Contact e-mail: cdecarli@ucdavis.edu Abstract not available.not available. SATURDAY, JULY 11, 2009 ALZHEIMER’S IMAGING CONSORTIUM PRESENTATIONS ORAL IC-O1 IC-O1-01 GENETIC PREDICTORS OF 12-MONTH CHANGE IN MRI HIPPOCAMPAL VOLUME IN THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE COHORT: ANALYSIS OF LEADING CANDIDATES FROM THE ALZGENE DATABASE Andrew J. Saykin, Li Shen, Shannon L. Risacher, Sungeun Kim, Kwangsik Nho, John D. West, Tatiana M. Foroud, and the Alzheimer’s Disease Neuroimaging Initiative, Indiana University School of Medicine, Indianapolis, IN, USA. Contact e-mail: asaykin@iupui.edu Background: High density genome-wide microarray data and one year longitudinal MRI data have become available for most participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a multi-center longitudinal study assessing imaging in the diagnosis and longitudinal monitoring of Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI). The AlzGene database provides meta-analytic data on leading candidate genes for AD. Here, we analyzed whether common variants in current major candidate genes could predict longitudinal changes on MRI. Methods: Baseline and 12 month T1-weighted MP-RAGE scans acquired on 1.5 T magnets from 627 ADNI participants (141 AD, 60 MCI-Converters, 241 MCI-Stable, 185 healthy controls, HC) were analyzed using Freesurfer software for automated parcellation and SPM5 for voxel-based morphometry (VBM). Genetic data consisted of APOE alleles and the Illumina 610 Quad array that includes over 620,000 features. For this analysis, common (minor allele frequency, MAF > 0.2) single nucleotide polymorphisms (SNPs) from the top 30 candidate genes from the AlzGene database were examined. Regression models were performed using SAS/Stat 9.3 to test the ability of SNPs to predict hippocampal volume and gray matter density changes. Results: Models including diagnosis group (AD, MCI-C, MCI-S, HC), SNP (0,1,2), parental history of dementia (0,1,2), APOE epsilon 4 status (0,1) and all interactions were computed. 732 SNPs were available for analysis with MAF> 0.2. A threshold of p 6 weeks before scanning. Memories were transcribed and scored, according to the Autobiographical Interview Scoring Manual (Levine et al, Psychology and Aging 2002). Results: While reported memories were of similar length, AD patients reported less episodic details (F(1,41) 1⁄4 17.70, P S). Controlling the data for performance, AD patients showed enhanced activity in LIFG, vmPFC, right precuneus and left lingual gyrus compared to healthy elderly. Also, AD patients had smaller hippocampi (t40 1⁄4 2.02, P < 0.05). Moreover, activation of LIFG and vmPFC was significantly negatively correlated with hippocampal volume in the AD patients only (r 1⁄4 -0.40, P < 0.05 and r 1⁄4 -0.37, P < 0.05), indicating the linking function of the hippocampus is moved to the vmPFC (like in consolidation), and patients rely more on semantic processing. Conclusions: AD patients attempt to compensate for their hippocampal damage/ autobiographical memory impairment by relying more on the vmPFC as a linking node and by increasing semantic processing. IC-O1-03 FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER’S DISEASE: COMPARISONS OF METABOLIC AND STRUCTURAL BRAIN ALTERATION EVOLUTIONS Nicolas Villain, Marine Fouquet, Brigitte Landeau, Mezenge Florence, Vincent de la Sayette, Fausto Viader, Jean-Claude Baron, Francis Eustache, Beatrice Desgranges, Gael Chetelat, Inserm-EPHE-Universite de Caen Basse-Normandie U923, Caen, France; Departement de Neurologie, CHU Cote de Nacre, Caen, France; Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom. Contact e-mail: villain@cyceron.fr Background: Several studies have highlighted the evolution of functional or structural brain alterations from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). They have pointed to a progression of brain atrophy within temporal, parietal and frontal lobes while metabolic decreases were restricted to frontal and cingulate areas. Crosssectional studies in AD led to a similar discrepancy between structural and functional alterations. This study aims at directly assessing the relationships and differences between the profiles of metabolic and morphological changes from aMCI to AD. Methods: Seventeen aMCI patients underwent both FDG-PET and T1-MRI examinations at inclusion (t0) and 18 months later (t18). At t18, seven of them fulfilled clinical criteria for probable AD (converters) while the others remained clinically stable (non-converters). For MRI data, we used VBM5.1 for segmentation and DARTEL for a two-step warping procedure (first to an intermediate ‘t0-t18’ subject template and second to a mean group template). The t0 Alzheimer’s Imaging Consortium: Oral IC-O1 P3