The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., Mazoyer, B., & Joliot, M. (2002) · NeuroImage · doi:10.1006/nimg.2001.0978 · Cited by 16,319
Self-citationNeuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798
A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains
Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0786 · Cited by 4,561
A PROPOSED MECHANISM OF EMOTION
PAPEZ, J. W. (1937) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1937.02260220069003 · Cited by 3,563
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268
Schmahmann, J. D., & Pandya, D. N. (2006) · doi:10.1093/acprof:oso/9780195104233.001.0001 · Cited by 1,157
Dynamics of Gray Matter Loss in Alzheimer's Disease
Thompson, P. M., Hayashi, K. M., de Zubicaray, G., Janke, A. L., Rose, S. E., Semple, J., Herman, D., Hong, M. S., Dittmer, S. S., Doddrell, D. M., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00994.2003 · Cited by 1,132
MRI Atlas of Human White Matter
Mori, S. (2005) · Cited by 1,103
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., & Powell, T. P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4531 · Cited by 987
Correction for partial volume effects in PET: principle and validation.
ROUSSET, O. G., Ma, Y., & Evans, A. C. (1998) · PubMed · Cited by 919
Wang, L. Y., Zang, Y., Yong He, A., Liang, M., Zhang, X., Tian, L., Wu, T., Jiang, T., & Li, K. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.033 · Cited by 867
Müller‐Gärtner, H. W., Links, J. M., Prince, J. L., Bryan, R. N., McVeigh, E. R., Leal, J. P., Davatzikos, C. A., & Frost, J. J. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.81 · Cited by 756
In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease
Baron, J., Chételat, G., Desgranges, B., Perchey, G., Landeau, B., Sayette, V. D. L., & Eustache, F. (2001) · NeuroImage · doi:10.1006/nimg.2001.0848 · Cited by 699
Self-citationWhitwell, J. L., Przybelski, S. A., Weigand, S. D., Knopman, D. S., Boeve, B. F., Petersen, R. C., & Jack, C. R. (2007) · Brain · doi:10.1093/brain/awm112 · Cited by 607
Chételat, G., Desgranges, B., Sayette, V. D. L., Viader, F., Eustache, F., & Baron, J. (2003) · Neurology · doi:10.1212/01.wnl.0000055847.17752.e6 · Cited by 606
Self-citationDuvernoy, H. M., Cattin, F., & Risold, P. (2013) · Springer eBooks · doi:10.1007/978-3-642-33603-4 · Cited by 569
Chételat, G., Landeau, B., Eustache, F., Mézenge, F., Viader, F., de la Sayette, V., Desgranges, B., & Baron, J.-C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.05.015 · Cited by 526
Self-citationDiffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease
Zhang, Y., Schuff, N. W., Jahng, G., Bayne, W., Mori, S., Schad, L. R., Mueller, S. G., Du, A., Kramer, J. H., Yaffe, K. S., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000250326.77323.01 · Cited by 513
Evidence from Functional Neuroimaging of a Compensatory Prefrontal Network in Alzheimer's Disease
Grady, C. L., McIntosh, A. R., Beig, S., Keightley, M., Burian, H., & Black, S. E. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00986.2003 · Cited by 504
White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study
Medina, D., deToledo-Morrell, L., Urresta, F., Gabrieli, J. D. E., Moseley, M., Fleischman, D., Bennett, D. A., Leurgans, S., Turner, D. A., & Stebbins, G. T. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.026 · Cited by 492
Macaque monkey retrosplenial cortex: III. Cortical efferents
Kobayashi, Y., & Amaral, D. G. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21346 · Cited by 487
Cytology and functionally correlated circuits of human posterior cingulate areas
Vogt, B. A., Vogt, L., & Laureys, S. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.07.048 · Cited by 484
Advances in the early detection of Alzheimer's disease
Nestor, P. J., Scheltens, P., & Hodges, J. R. (2004) · Nature Medicine · doi:10.1038/nrn1433 · Cited by 480
Rose, S. (2000) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.69.4.528 · Cited by 465
Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment
Chételat, G., Desgranges, B., de la Sayette, V., Viader, F., Eustache, F., & Baron, J. (2002) · NeuroReport · doi:10.1097/00001756-200210280-00022 · Cited by 405
Self-citationMacaque monkey retrosplenial cortex: II. Cortical afferents
Kobayashi, Y., & Amaral, D. G. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10883 · Cited by 387
Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease
Grady, C. L. (2001) · Brain · doi:10.1093/brain/124.4.739 · Cited by 379
Reduced Hippocampal Functional Connectivity in Alzheimer Disease
Allen, G., Barnard, H. D., McColl, R. W., Hester, A. L., Fields, J. A., Weiner, M., Ringe, W. K., Lipton, A. M., Brooker, M., McDonald, E. C., et al. (2007) · Archives of Neurology · doi:10.1001/archneur.64.10.1482 · Cited by 360
Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease
Chételat, G., Desgranges, B., Landeau, B., Mézenge, F., Poline, J.-B., Sayette, V. D. L., Viader, F., Eustache, F., & Baron, J. (2007) · Brain · doi:10.1093/brain/awm288 · Cited by 349
Self-citationDesgranges, B. (1998) · Brain · doi:10.1093/brain/121.4.611 · Cited by 326
Self-citationFellgiebel, A., Wille, P., Müller, M. J., Winterer, G., Scheurich, A., Vucurevic, G., Schmidt, L. G., & Stoeter, P. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000077817 · Cited by 298
Some observations on the course and composition of the cingulum bundle in the rhesus monkey
Mufson, E. J., & Pandya, D. Ν. (1984) · The Journal of Comparative Neurology · doi:10.1002/cne.902250105 · Cited by 277
Fellgiebel, A., Müller, M. J., Wille, P. R., Dellani, P. R., Scheurich, A., Schmidt, L., & Stoeter, P. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.11.006 · Cited by 266
Hirao, K., Ohnishi, T., Hirata, Y., Yamashita, F., Mori, T., Moriguchi, Y., Matsuda, H., Nemoto, K., Imabayashi, E., Yamada, M., et al. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.06.066 · Cited by 265
Cortical variability and asymmetry in normal aging and Alzheimer's disease
Thompson, P. M. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.6.492 · Cited by 264
Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment
Chetelat, G. (2003) · Brain · doi:10.1093/brain/awg196 · Cited by 264
Meguro, K., Blaizot, X., Kondoh, Y., Mestric, C. L., Baron, J., & Chavoix, C. (1999) · Brain · doi:10.1093/brain/122.8.1519 · Cited by 228
Self-citationNestor, P. J., Fryer, T. D., Ikeda, M., & Hodges, J. R. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02999.x · Cited by 227
Quarantelli, M., Berkouk, K., Prinster, A., Landeau, B., Svarer, C., Balkay, L., Alfano, B., Brunetti, A., Baron, J., & Salvatore, M. (2004) · PubMed · Cited by 224
Self-citationHuang, J., Friedland, R. P., & Auchus, A. P. (2007) · American Journal of Neuroradiology · doi:10.3174/ajnr.a0700 · Cited by 220
Morris, R., Pandya, D. Ν., & Petrides, M. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990503)407:2 · Cited by 219
Voxel-based detection of white matter abnormalities in mild Alzheimer disease
Xie, S., Xiao, J., Gong, G., Zang, Y., Wang, Y., Wu, H., & Jiang, X. X. (2006) · Neurology · doi:10.1212/01.wnl.0000219625.77625.aa · Cited by 208
Stoub, T. R., deToledo‐Morrell, L., Stebbins, G. T., Leurgans, S. E., Bennett, D. A., & Shah, R. C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603414103 · Cited by 207
Imaging the progression of Alzheimer pathology through the brain
Smith, A. D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082107399 · Cited by 202
Rémy, F., Mirrashed, F., Campbell, B. I., & Richter, W. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.10.045 · Cited by 200
Multivariate network analysis of fiber tract integrity in Alzheimer’s disease
Teipel, S. J., Stahl, R., Dietrich, O., Schoenberg, S. O., Perneczky, R., Bokde, A. L. W., Reiser, M. F., Möller, H., & Hampel, H. J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.07.047 · Cited by 169
Jobst, K. A., Smith, A. D., Barker, C. S., Wear, A., King, E. M., Smith, A. D., Anslow, P., Molyneux, A., SHEPSTONE, B. J., & Soper, N. (1992) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.55.3.190 · Cited by 163
Matsuda, H., Kitayama, N., Ohnishi, T., Asada, T., Nakano, S., Sakamoto, S., Imabayashi, E., & Katoh, A. (2002) · PubMed · Cited by 157
Estimating Smoothness in Statistical Parametric Maps
Poline, J., Worsley, K. J., Holmes, A. P., Frackowiak, R. S. J., & Friston, K. J. (1995) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199509000-00017 · Cited by 143
Meguro, K. (2001) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.71.3.315 · Cited by 119
Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s disease
Kawachi, T., Ishii, K., Sakamoto, S., Sasaki, M., Mori, T., Yamashita, F., Matsuda, H., & Mori, E. (2006) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-005-0050-x · Cited by 112
Richardson, M. P. (1997) · Brain · doi:10.1093/brain/120.11.1961 · Cited by 112
Garrido, G. E. J. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.5.508 · Cited by 91
Mevel, K., Desgranges, B., Baron, J., Landeau, B., Sayette, V. D. L., Viader, F., Eustache, F., & Chételat, G. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.04.048 · Cited by 90
Self-citationFirbank, M., Blamire, A. M., Krishnan, M. S., Teodorczuk, A., English, P. T., Gholkar, A. R., Harrison, R. M., & O'Brien, J. T. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.02.027 · Cited by 88
Ishii, K., Sasaki, H., Kono, A. K., Miyamoto, N., Fukuda, T., & Mori, E. (2005) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-004-1740-5 · Cited by 88
Chaim, T. M., Duran, F., Uchida, R. R., Périco, C. D. A.-M., de Castro, C. C., & Busatto, G. F. (2006) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2006.04.003 · Cited by 80
Evaluation of bilateral cingulum with tractography in patients with Alzheimer’s disease
Xie, S., Xiao, J. X., Wang, Y. H., Wu, H. K., Gong, G. L., & Jiang, X. X. (2005) · NeuroReport · doi:10.1097/01.wnr.0000174061.41897.ee · Cited by 68
Van Laere, K. J., & Dierckx, R. A. (2001) · Radiology · doi:10.1148/radiol.2213010295 · Cited by 67
Machado, C. J., Snyder, A. Z., Cherry, S. R., Lavenex, P., & Amaral, D. G. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.029 · Cited by 36
Haxby, J. V., & Rapoport, S. I. (1986) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(86)90016-3 · Cited by 35
Cited by
Sorted by citations
What does the retrosplenial cortex do?
Vann, S. D., Aggleton, J. P., & Maguire, E. A. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2733 · Cited by 1,409
A network diffusion model of disease progression in dementia
Raj, A., Kuceyeski, A., & Weiner, M. (2012) · Neuron · doi:10.1016/j.neuron.2011.12.040 · Cited by 723
Sanz-Arigita, E. J., Schoonheim, M. M., Damoiseaux, J. S., Rombouts, S. A. R. B., Maris, E., Barkhof, F., Scheltens, P., & Stam, C. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013788 · Cited by 608
Resting state fMRI in Alzheimer's disease: beyond the default mode network
Agosta, F., Pievani, M., Geroldi, C., Copetti, M., Frisoni, G. B., & Filippi, M. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.06.007 · Cited by 599
Chris Hinrichs, A., Singh, V., Xu, G., & Johnson, S. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.10.081 · Cited by 416
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
