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Aging and disease    2016, Vol. 7 Issue (5) : 553-560     DOI: 10.14336/AD.2016.0305
Original Article |
Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer’s Disease
Baumgaertel Johanna1, Haussmann Robert1, Gruschwitz Antonia1, Werner Annett3, Osterrath Antje1,2, Lange Jan1, Donix Katharina L.1, Linn Jennifer3, Donix Markus1,2,*
1Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
2DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany
3Department of Neuroradiology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer’s disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer’s disease patients underwent 3T magnetic resonance imaging. We applied a cortical unfolding approach to investigate individual subregions of the medial temporal lobe. Among patients homozygous for the APOE4 genotype or carrying both APOE4 and family history risks, lower education was associated with a thinner cortex in multiple medial temporal regions, including the hippocampus. Our data suggest that the years of formal education and genetic risks interact in their influence on hippocampal structure in Alzheimer’s disease patients.

Keywords hippocampus      apolipoprotein E      cognitive reserve      education     
Corresponding Authors: Donix Markus   
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These authors contributed equally to the work

Issue Date: 01 October 2016
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Baumgaertel Johanna
Haussmann Robert
Gruschwitz Antonia
Werner Annett
Osterrath Antje
Lange Jan
Donix Katharina L.
Linn Jennifer
Donix Markus
Cite this article:   
Baumgaertel Johanna,Haussmann Robert,Gruschwitz Antonia, et al. Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer’s Disease[J]. Aging and disease, 2016, 7(5): 553-560.
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Figure 1.  Cortical unfolding. After oblique coronal MRI scanning and manual segmentation of white matter and CSF on the T2 weighted MRI sequence, the resulting gray matter volume is computationally unfolded and flattened based on metric multidimensional scaling [right hemispheric flatmap shown, B]. Boundaries between the subregions are delineated on the original high-resolution MRI sequence (A) and later mathematically projected to flat map space. CA23DG=cornu ammonis fields 2,3 and dentate gyrus (the anterior part of the cornu ammonis fields and dentate gyrus [ant. CADG] is part of the CA23DG region), CA1=CA field 1, SUB=subiculum, ERC=entorhinal cortex, PRC=perirhinal cortex, PHC=parahippocampal cortex, FUS=fusiform cortex (fusiform boundary depicts the medial fusiform vertex).
Characteristics and MeasuresLower
Age (years)71.8± 7.073.8±6.30.25
Female sex (no.)1890.1
Education (years)11.5± 1.216.2±1.7< 0.001
APOE status (no.)
First degree family history of AD (no.)9130.09
MMSE (score range 0-30)21.1± 5.224.7± 4.20.033
Table 1  Demographic characteristics and neuropsychological scores.
Figure 2.  Correlation of education and cortical thickness. The figure illustrates the association of the years of education and cortical thickness across medial temporal subregions (legend see Figure 1). Patients homozygous for the APOE4 allele or APOE4 carriers with a first-degree family history of Alzheimer’s disease showed a positive correlation of education and thickness in all regions except CA1. Patients with an intermediate risk profile (APOE4 heterozygosis or family history risk) showed this correlation only in PHC with trends for other regions, such as the ERC. Patients in the low risk group (no APOE4 allele and no family history) did not show an association between education and thickness.
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