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The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease
Tahmasian M, Pasquini L, Scherr M, Meng C, Förster S, Mulej Bratec S, Shi K, Yakushev I et al.. Neurology, 2015-04-15
Topic: Amyloid, tau and blood-test diagnosis
Objectives Based on the hippocampus disconnection hypothesis in Alzheimer disease (AD), which postulates that uncoupling from cortical inputs contributes to disinhibition-like changes in hippocampus activity, we suggested that in patients with AD, the more the intrinsic functional connectivity between hippocampus and precuneus is decreased, the higher hippocampal glucose metabolism will be. Methods Forty patients with mild AD dementia, 21 patients with mild cognitive impairment, and 26 healthy controls underwent simultaneous PET/MRI measurements on an integrated PET/MR scanner. (18)F-fluorodeoxyglucose-PET was used to measure local glucose metabolism as proxy for neural activity, and resting-state functional MRI with seed-based functional connectivity analysis was performed to measure intrinsic functional connectivity as proxy for neural coupling. Group comparisons and correlation analysis were corrected for effects of regional atrophy, partial volume effect, age, and sex. Results In both patient groups, intrinsic connectivity between hippocampus and precuneus was significantly reduced. Moreover, in both patient groups, glucose metabolism was reduced in the precuneus (AD Conclusion Results provide evidence that in patients with AD dementia, stronger decrease of intrinsic connectivity between hippocampus and precuneus is linked with higher intrahippocampal metabolism (probably reflecting higher neuronal activity). These data support the hippocampus disconnection hypothesis, i.e., uncoupling from cortical inputs may contribute to disinhibition-like changes of hippocampal activity with potentially adverse consequences on both intrahippocampal physiology and clinical outcome.
Key findings
- Objectives Based on the hippocampus disconnection hypothesis in Alzheimer disease (AD), which postulates that uncoupling from cortical inputs contributes to disinhibition-like changes in hippocampus activity, we suggested that in patients with AD, the more the intrinsic functional connectivity between hippocampus and precuneus is decreased, the higher hippocampal glucose metabolism will be.
- Results In both patient groups, intrinsic connectivity between hippocampus and precuneus was significantly reduced.
- Moreover, in both patient groups, glucose metabolism was reduced in the precuneus (AD < mild cognitive impairment < controls) while unchanged in the hippocampus.
Why it matters
In patients with mild cognitive impairment and mild Alzheimer's dementia, weaker connectivity between the hippocampus and precuneus was linked to higher glucose metabolism within the hippocampus itself. This supports the idea that lost input from other brain regions may change hippocampal activity, but it does not test any treatment.
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Study details
- Participants21
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 21 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 112 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.6 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 9.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alexander E. Drzezga: h-index 88 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Technical University of Munich: institution h-index 1,092 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25878180) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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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
Tahmasian, M., Pasquini, L., Scherr, M., Meng, C., Förster, S., Mulej Bratec, S., et al. (2015). The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000001575
Vancouver
Tahmasian M, Pasquini L, Scherr M, Meng C, Förster S, Mulej Bratec S, et al. The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease. Neurology. 2015. doi:10.1212/wnl.0000000000001575. PMID: 25878180.
BibTeX
@article{tahmasian2015-25878180,
author = {Tahmasian, M. and Pasquini, L. and Scherr, M. and Meng, C. and Förster, S. and Mulej Bratec, S. and Shi, K. and Yakushev, I. and others},
title = {{The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease}},
journal = {Neurology},
year = {2015},
doi = {10.1212/wnl.0000000000001575},
pmid = {25878180},
url = {https://doi.org/10.1212/wnl.0000000000001575}
}
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