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APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD
OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brai...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039513/ https://www.ncbi.nlm.nih.gov/pubmed/24878738 http://dx.doi.org/10.1371/journal.pone.0097608 |
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author | Manning, Emily N. Barnes, Josephine Cash, David M. Bartlett, Jonathan W. Leung, Kelvin K. Ourselin, Sebastien Fox, Nick C. |
author_facet | Manning, Emily N. Barnes, Josephine Cash, David M. Bartlett, Jonathan W. Leung, Kelvin K. Ourselin, Sebastien Fox, Nick C. |
author_sort | Manning, Emily N. |
collection | PubMed |
description | OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD. |
format | Online Article Text |
id | pubmed-4039513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40395132014-06-02 APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD Manning, Emily N. Barnes, Josephine Cash, David M. Bartlett, Jonathan W. Leung, Kelvin K. Ourselin, Sebastien Fox, Nick C. PLoS One Research Article OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD. Public Library of Science 2014-05-30 /pmc/articles/PMC4039513/ /pubmed/24878738 http://dx.doi.org/10.1371/journal.pone.0097608 Text en © 2014 Manning et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Manning, Emily N. Barnes, Josephine Cash, David M. Bartlett, Jonathan W. Leung, Kelvin K. Ourselin, Sebastien Fox, Nick C. APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title |
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title_full |
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title_fullStr |
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title_full_unstemmed |
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title_short |
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD |
title_sort | apoe ε4 is associated with disproportionate progressive hippocampal atrophy in ad |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039513/ https://www.ncbi.nlm.nih.gov/pubmed/24878738 http://dx.doi.org/10.1371/journal.pone.0097608 |
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