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Gender, apolipoprotein E genotype, and mesial temporal atrophy: 2-year follow-up in patients with stable mild cognitive impairment and with progression from mild cognitive impairment to Alzheimer’s disease

  • Functional Neuroradiology
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Abstract

Introduction

This study aimed to examine the relationship between gender, apolipoprotein E (APOE) genotype, and mesial temporal atrophy in mild cognitive impairment (MCI) with and without progression to Alzheimer’s disease (AD).

Methods

We evaluated 236 MCI patients with (n = 121) and without (n = 115) AD progression. Longitudinal MRI-based hippocampal volumes (HV) and entorhinal cortex (ERC) thickness were obtained. The Clinical Dementia Rating Sum of Boxes (CDR-SB) score was used to assess disease severity.

Results

We found a significant effect of APOE, gender, and clinical course (stable MCI versus MCI-AD progression) on HV. There was a significant effect of clinical course and APOE, but not gender, on ERC. Baseline HV and APOE4 status predicted MCI-AD progression in women. Baseline ERC and APOE4 status predicted MCI-AD progression in men. There were significant differences in CDR-SB scores between patients with and without MCI-AD progression, but not between males and females, or APOE4 carriers and non-carriers.

Conclusions

HV, but not ERC, is strongly influenced by gender in MCI. The effects of gender and APOE4 on neuroimaging biomarkers have potentially important implications in the prediction of MCI-AD progression and should be taken into account in clinical trials.

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Acknowledgments

Data collection and sharing for this project were 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.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by 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 of Southern California.

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Authors and Affiliations

  1. Department of Radiology and Radiological Science, Medical University of South Carolina, 96 Jonathan Lucas Street, MSC 323, Charleston, SC, 29401, USA

    M. V. Spampinato, K. E. Patrick, H. Collins & E. Pravata’

  2. Department of Internal Medicine, Medical University of South Carolina, Charleston, SC, USA

    B. R. Langdon

  3. Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA

    R. O. Parker

  4. Department of Neuroradiology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland

    E. Pravata’

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  1. M. V. Spampinato
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For the Alzheimer’s Disease Neuroimaging Initiative

Corresponding author

Correspondence to M. V. Spampinato.

Ethics declarations

We declare that all human and animal studies have been approved by the Medical University of South Carolina Institutional Review Board and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.

Additional information

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (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 the analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Appendix 1

Appendix 1

ADNI study protocol summary

Enrolled subjects were between 55 and 90 (inclusive) years of age, had a study partner able to provide an independent evaluation of functioning, and spoke either English or Spanish. All subjects were willing and able to undergo all test procedures including neuroimaging and agreed to longitudinal follow up. Between 20 and 50 % must have been willing to undergo two lumbar punctures, spaced 1 year apart. Specific psychoactive medications were excluded. General inclusion/exclusion criteria for the MCI subjects enrolled in the ADNI 1 study were as follows:

MCI subjects

MMSE scores between 24 and 30 (inclusive), a memory complaint, have objective memory loss measured by education-adjusted scores on Wechsler Memory Scale Logical Memory II, a CDR of 0.5, absence of significant levels of impairment in cognitive domains other than memory, essentially preserved activities of daily living, and an absence of dementia.

All subjects underwent clinical/cognitive assessments and 1.5 T structural MRI at specified intervals (6 or 12 months) for 2–3 years. Approximately 50 % of the subjects also had FDG PET scans at the same time intervals. MCI subjects at high risk for conversion to AD (n = 400) were studied at 0, 6, 12, 18, 24, and 36 months. All MRI and PET scans were rapidly assessed for quality so that subjects may be rescanned if necessary. All clinical data were collected, monitored, and stored by the Coordinating Center at the ADCS. University of Pennsylvania collected biomarker samples. All raw and processed image data were archived at LONI.

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Spampinato, M.V., Langdon, B.R., Patrick, K.E. et al. Gender, apolipoprotein E genotype, and mesial temporal atrophy: 2-year follow-up in patients with stable mild cognitive impairment and with progression from mild cognitive impairment to Alzheimer’s disease. Neuroradiology 58, 1143–1151 (2016). https://doi.org/10.1007/s00234-016-1740-8

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