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Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Published online by Cambridge University Press:  05 March 2020

Margaret Abraham ,
Michael Seidenberg ,
Dana A. Kelly ,
Kristy A. Nielson ,
John L. Woodard ,
J. Carson Smith ,
Sally Durgerian  and
Stephen M. Rao
Margaret Abraham
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Michael Seidenberg
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Dana A. Kelly
Affiliation:
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL60064, USA
Kristy A. Nielson
Affiliation:
Department of Psychology, Marquette University, Milwaukee, WI53226, USA Department of Neurology, Medical College of Wisconsin, Milwaukee, WI53226, USA
John L. Woodard
Affiliation:
Department of Psychology, Wayne State University, Detroit, MI48202, USA
J. Carson Smith
Affiliation:
Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD20740, USA
Sally Durgerian
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI53226, USA
Stephen M. Rao*
Affiliation:
Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH44195, USA
*
*Correspondence and reprint requests to: Stephen M. Rao, PhD, Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue/U10, Cleveland, OH44195, USA, E-mail: raos2@ccf.org
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Abstract

Objective:

The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.

Methods:

Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.

Results:

At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.

Conclusions:

Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

Keywords

Mild cognitive impairmentAlzheimer diseaseRisk factorsMRIHippocampusLongitudinal studies
Type
Brief Communication
Information
Journal of the International Neuropsychological Society , Volume 26 , Issue 7 , August 2020 , pp. 733 - 738
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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