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APOE-dependent phenotypes in subjects with mild cognitive impairment converting to Alzheimer's disease

Item Type:Article
Title:APOE-dependent phenotypes in subjects with mild cognitive impairment converting to Alzheimer's disease
Creators Name:Morgen, K. and Froelich, L. and Tost, H. and Plichta, M.M. and Koelsch, H. and Rakebrandt, F. and Rienhoff, O. and Jessen, F. and Peters, O. and Jahn, H. and Luckhaus, C. and Huell, M. and Gertz, H.J. and Schroeder, J. and Hampel, H. and Teipel, S.J. and Pantel, J. and Heuser, I. and Wiltfang, J. and Ruether, E. and Kornhuber, J. and Maier, W. and Meyer-Lindenberg, A.
Abstract:Background: The E4 isoform of the APOE genotype is the most significant genetic risk factor for sporadic Alzheimer's disease (AD) and has recently been found to modulate disease expression in patients with AD. Objective: To investigate APOE-dependent cognitive and structural phenotypes in subjects with mild cognitive impairment who converted to AD within the following three years. Methods: Subjects converting to AD (n = 63) were compared to a control group with stable mild cognitive impairment (n = 131). Clinical, neuropsychological, and MRI data were obtained by the German Dementia Competence Network. Subgroups of converting and stable APOE E4 carriers and non-carriers were investigated longitudinally with MRI to examine structural correlates of conversion. Voxel-based morphometry was applied to investigate gray matter distribution. Results: At baseline, executive performance correlated with global and bilateral prefrontal gray matter volume and predicted conversion only among non-carriers. Converting carriers and non-carriers presented distinct patterns of brain atrophy on longitudinal analysis, in line with a dissociation between more pronounced occipital atrophy in carriers and more frontoparietal volume loss in non-carriers at follow-up. Conclusions: The current findings suggest that in APOE E4 non-carriers with AD, executive dysfunction is closely linked to frontal gray matter atrophy and predictive of progression to dementia. The results are consistent with APOE genotype-dependent profiles of structural damage and cognitive decline in patients with imminent conversion to AD.
Keywords:APOE, Alzheimer's Disease, Magnetic Resonance Imaging, Mild Cognitive Impairment, Phenotypes, Voxel-Based Morphometry
Source:Journal of Alzheimer's Disease
Publisher:IOS Press
Page Range:389-401
Date:3 July 2013
Official Publication:https://doi.org/10.3233/JAD-130326
PubMed:View item in PubMed

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