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Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study

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Abstract

APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE ε2 carriers, 54 APOE ε4 carriers and 90 ε3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson’s correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with ε4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in ε4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson’s correlation analysis showed parietal WMH volume was significantly related with IPS, especially in ε4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE ε4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in ε4 carriers, was independently contributed to slower IPS.

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Acknowledgments

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.;Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; ElanPharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliatedcompany Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen AlzheimerImmunotherapy Research & Development, LLC.; Johnson & Johnson PharmaceuticalResearch & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; MesoScaleDiagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis PharmaceuticalsCorporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; andTransition Therapeutics. The Canadian Institutes of Health Research is providing funds tosupport ADNI clinical sites in Canada. Private sector contributions are facilitated by theFoundation for the National Institutes of Health (www.fnih.org). The grantee organization isthe Northern California Institute for Research and Education, and the study is coordinatedby the Alzheimer’s Disease Cooperative Study at the University of California, San Diego.ADNI data are disseminated by the Laboratory for Neuro Imaging at the University ofSouthern California.

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  1. Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jiefang Road, Shangcheng District, Hangzhou, China

    Xiao Luo, Yerfan Jiaerken, Xinfeng Yu, Peiyu Huang, Tiantian Qiu, Yunlu Jia, Jianzhong Sun & Minming Zhang

  2. Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

    Jiong Zhou

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  1. Xiao Luo
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Correspondence to Minming Zhang.

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The authors declare that they have no conflict of interest.

Ethical approval

“All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”

Informed consent

Written informed consent was obtained from all participants and/or authorized representatives and the study partners before any protocol-specific procedures were carried out in the ADNI study. More details in http://www.adni-info.org.

Funding

This study was funded by the 12th Five-year Plan for National Science and Technology Supporting Program of China (Grant No. 2012BAI10B04), Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ14H180001 and Grant No. Y16H090026).

Additional information

Xiao Luo and Yerfan Jiaerken contributed equally to this work.

Data used in preparation of this article were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database (www.adni.loni.usc.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.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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Luo, X., Jiaerken, Y., Yu, X. et al. Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study. Brain Imaging and Behavior 11, 977–985 (2017). https://doi.org/10.1007/s11682-016-9571-0

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