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Research ArticleAdult Brain
Open Access

APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline

S. Haller, M.-L. Montandon, C. Rodriguez, M. Ackermann, F.R. Herrmann and P. Giannakopoulos
American Journal of Neuroradiology July 2017, 38 (7) 1335-1342; DOI: https://doi.org/10.3174/ajnr.A5184
S. Haller
aFrom the Affidea Centre de Diagnostic Radiologique de Carouge (S.H.), Geneva, Switzerland
bFaculty of Medicine (S.H., M.-L.M., F.R.H., P.G.), University of Geneva, Switzerland
cDepartments of Surgical Sciences and Radiology (S.H.), Uppsala University, Uppsala, Sweden
dDepartment of Neuroradiology (S.H.), University Hospital Freiburg, Freiburg, Germany
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M.-L. Montandon
bFaculty of Medicine (S.H., M.-L.M., F.R.H., P.G.), University of Geneva, Switzerland
eDepartment of Mental Health and Psychiatry (M.-L.M., M.A.)
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C. Rodriguez
fDivision of Institutional Measures, Medical Direction (C.R., P.G.)
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M. Ackermann
eDepartment of Mental Health and Psychiatry (M.-L.M., M.A.)
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F.R. Herrmann
bFaculty of Medicine (S.H., M.-L.M., F.R.H., P.G.), University of Geneva, Switzerland
gDivision of Geriatrics, Department of Internal Medicine, Rehabilitation and Geriatrics (F.R.H.), University Hospitals of Geneva, Geneva, Switzerland.
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P. Giannakopoulos
bFaculty of Medicine (S.H., M.-L.M., F.R.H., P.G.), University of Geneva, Switzerland
fDivision of Institutional Measures, Medical Direction (C.R., P.G.)
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Abstract

BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline.

MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM.

RESULTS: APOE*E4-related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE*E4-related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up.

CONCLUSIONS: APOE*E4-related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE*E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe.

ABBREVIATIONS:

AD
Alzheimer disease
APOE
apolipoprotein E
dCON
cognitively deteriorating controls
MCI
mild cognitive impairment
sCON
cognitively stable controls
  • © 2017 by American Journal of Neuroradiology

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American Journal of Neuroradiology: 38 (7)
American Journal of Neuroradiology
Vol. 38, Issue 7
1 Jul 2017
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S. Haller, M.-L. Montandon, C. Rodriguez, M. Ackermann, F.R. Herrmann, P. Giannakopoulos
APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline
American Journal of Neuroradiology Jul 2017, 38 (7) 1335-1342; DOI: 10.3174/ajnr.A5184

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APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline
S. Haller, M.-L. Montandon, C. Rodriguez, M. Ackermann, F.R. Herrmann, P. Giannakopoulos
American Journal of Neuroradiology Jul 2017, 38 (7) 1335-1342; DOI: 10.3174/ajnr.A5184
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