Applying surface-based hippocampal morphometry to study APOE-E4 allele dose effects in cognitively unimpaired subjects

Qunxi Dong; Wen Zhang; Jianfeng Wu; Bolun Li; Emily H Schron; Travis McMahon; Jie Shi; Boris A Gutman; Kewei Chen; Leslie C Baxter; Paul M Thompson; Eric M Reiman; Richard J Caselli; Yalin Wang

doi:10.1016/j.nicl.2019.101744

Applying surface-based hippocampal morphometry to study APOE-E4 allele dose effects in cognitively unimpaired subjects

Neuroimage Clin. 2019:22:101744. doi: 10.1016/j.nicl.2019.101744. Epub 2019 Mar 4.

Authors

Qunxi Dong¹, Wen Zhang¹, Jianfeng Wu¹, Bolun Li¹, Emily H Schron², Travis McMahon¹, Jie Shi¹, Boris A Gutman³, Kewei Chen⁴, Leslie C Baxter⁵, Paul M Thompson⁶, Eric M Reiman⁴, Richard J Caselli⁷, Yalin Wang⁸

Affiliations

¹ School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, AZ, USA.
² Wellesley College, Wellesley, MA, USA.
³ Armour College of Engineering, Illinois Institute of Technology, Chicago, IL, USA.
⁴ Banner Alzheimer's Institute, Phoenix, AZ, USA.
⁵ Human Brain Imaging Laboratory, Barrow Neurological Institute, Phoenix, AZ, USA.
⁶ Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
⁷ Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
⁸ School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, AZ, USA. Electronic address: ylwang@asu.edu.

Abstract

Apolipoprotein E (APOE) e4 is the major genetic risk factor for late-onset Alzheimer's disease (AD). The dose-dependent impact of this allele on hippocampal volumes has been documented, but its influence on general hippocampal morphology in cognitively unimpaired individuals is still elusive. Capitalizing on the study of a large number of cognitively unimpaired late middle aged and older adults with two, one and no APOE-e4 alleles, the current study aims to characterize the ability of our automated surface-based hippocampal morphometry algorithm to distinguish between these three levels of genetic risk for AD and demonstrate its superiority to a commonly used hippocampal volume measurement. We examined the APOE-e4 dose effect on cross-sectional hippocampal morphology analysis in a magnetic resonance imaging (MRI) database of 117 cognitively unimpaired subjects aged between 50 and 85 years (mean = 57.4, SD = 6.3), including 36 heterozygotes (e3/e4), 37 homozygotes (e4/e4) and 44 non-carriers (e3/e3). The proposed automated framework includes hippocampal surface segmentation and reconstruction, higher-order hippocampal surface correspondence computation, and hippocampal surface deformation analysis with multivariate statistics. In our experiments, the surface-based method identified APOE-e4 dose effects on the left hippocampal morphology. Compared to the widely-used hippocampal volume measure, our hippocampal morphometry statistics showed greater statistical power by distinguishing cognitively unimpaired subjects with two, one, and no APOE-e4 alleles. Our findings mirrored previous studies showing that APOE-e4 has a dose effect on the acceleration of brain structure deformities. The results indicated that the proposed surface-based hippocampal morphometry measure is a potential preclinical AD imaging biomarker for cognitively unimpaired individuals.

Keywords: APOE-e4; Alzheimer's disease; Cognitively unimpaired; Hippocampal morphometry; Magnetic resonance imaging (MRI).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alleles*
Apolipoprotein E4 / genetics*
Cognition / physiology*
Female
Gene Dosage / genetics*
Hippocampus / diagnostic imaging*
Hippocampus / physiology*
Humans
Male
Middle Aged

Substances

Apolipoprotein E4

Abstract

Publication types

MeSH terms

Substances

Grants and funding