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APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults

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Abstract

The APOE ε4 allele is associated with cognitive deficits and brain atrophy in older adults, but studies in younger adults are mixed. We examined APOE genotype effects on cognition and brain structure in younger adults and whether genotype effects differed by age and with presence of depression. 157 adults (32 % ε4 carriers, 46 % depressed) between 20 and 50 years of age completed neuropsychological testing, 131 of which also completed 3 T cranial MRI. We did not observe a direct effect of APOE genotype on cognitive performance or structural MRI measures. A significant genotype by age interaction was observed for executive function, where age had less of an effect on executive function in ε4 carriers. Similar interactions were observed for the entorhinal cortex, rostral and caudal anterior cingulate cortex and parahippocampal gyrus, where the effect of age on regional volumes was reduced in ε4 carriers. There were no significant interactions between APOE genotype and depression diagnosis. The ε4 allele benefits younger adults by allowing them to maintain executive function performance and volumes of cingulate and temporal cortex regions with aging, at least through age fifty years.

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Acknowledgments

This project was supported by National Institute of Mental Health (NIMH) grant R01 MH077745. It was further supported by CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences (NCATS) and conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN.

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Authors and Affiliations

  1. The Geriatric Research, Education, and Clinical Center (GRECC), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, 37212, USA

    Warren D. Taylor & Ayman Saleh

  2. The Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University Medical Center, 1601 23rd Avenue South, Nashville, TN, 37212, USA

    Warren D. Taylor, Brian Boyd & Rachel Turner

  3. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27710, USA

    Douglas R. McQuoid & Guy G. Potter

  4. Center for Human Disease Modeling and Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    Allison Ashley-Koch

  5. Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA

    James R. MacFall

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  1. Warren D. Taylor
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All authors (including Dr. Taylor, Mr. Boyd, Ms. Turner, Mr. McQuoid, Dr. Ashley-Koch, Dr. MacFall, Dr. Saleh, and Dr. Potter) declare they have no conflict of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Taylor, W.D., Boyd, B., Turner, R. et al. APOE ε4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults. Brain Imaging and Behavior 11, 194–204 (2017). https://doi.org/10.1007/s11682-016-9522-9

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