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Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease
Villain N, Fouquet M, Baron JC, Baron JC, Mézenge F, Landeau B, de La Sayette V, Viader F et al.. Brain : a journal of neurology, 2010-08-05
Topic: Amyloid, tau and blood-test diagnosis
Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.
Key findings
- We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³).
- These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively.
Why it matters
In patients with amnestic mild cognitive impairment, this study found sequential relationships in which baseline hippocampal atrophy was linked to later cingulum bundle and uncinate fasciculus atrophy, which in turn was linked to later decline in cingulate and subgenual metabolism. The findings describe a sequence of brain changes in early Alzheimer's disease, not a treatment.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 60/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 239 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.3 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 14.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gaël Chételat: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20688814) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Villain, N., Fouquet, M., Baron, J. C., Mézenge, F., Landeau, B., de La Sayette, V., et al. (2010). Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awq203
Vancouver
Villain N, Fouquet M, Baron JC, Mézenge F, Landeau B, de La Sayette V, et al. Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease. Brain : a journal of neurology. 2010. doi:10.1093/brain/awq203. PMID: 20688814.
BibTeX
@article{villain2010-20688814,
author = {Villain, N. and Fouquet, M. and Baron, J. C. and Mézenge, F. and Landeau, B. and de La Sayette, V. and Viader, F. and others},
title = {{Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease}},
journal = {Brain : a journal of neurology},
year = {2010},
doi = {10.1093/brain/awq203},
pmid = {20688814},
url = {https://doi.org/10.1093/brain/awq203}
}
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