Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer's disease
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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.
“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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- 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
- Health Sciences › Medicine › Physiology › 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
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