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Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease
Open accessAbstract
In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.
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“hippocampal atrophy has been shown to induce PCC hypometabolism through a disconnection process in AD (Villain et al., 2008).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Villain et al., 2008
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Metadata
- Authors
- Villain, N., Desgranges, B., Viader, F., de la Sayette, V., Mezenge, F., Landeau, B., Baron, J.-C., Eustache, F., & Chetelat, G.
- Affiliations
- Inserm (FR)
- University of Cambridge (GB)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-06-11
- Volume
- 28
- Issue
- 24
- Pages
- 6174-6181
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2902815
- OpenAlex
- W2050214509
- Cited by
- 366
- References
- 63
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 19 · 2020: 15 · 2019: 16 · 2018: 16 · 2017: 21 · 2016: 25 · 2015: 25 · 2014: 27 · 2013: 38 · 2012: 22
- FWCI
- 21.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Association France Alzheimer
- Région Normandie
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, hippocampal atrophy, cingulum, white matter disruption, Papez circuit, memory circuits, thalamus, mammillary bodies, parahippocampal gyrus, posterior association cortex, disconnection hypothesis, glucose hypometabolism
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain Mapping, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuroglia, Neurons, Neuropsychological Tests, Statistics as Topic, Case-Control Studies, Fluorodeoxyglucose F18, Positron-Emission Tomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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