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Structural and metabolic topological alterations associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, double-blind, placebo-controlled trial
Han X, Gong S, Gong J, Wang P, Li R, Chen R, Xu C, Sun W et al.. Psychiatry and clinical neurosciences, 2025-03-31
Topic: Brain proteins, microglia and lab models
Aims Effective intervention for mild cognitive impairment (MCI) is key for preventing dementia. As a neuroprotective agent, butylphthalide has the potential to treat MCI due to Alzheimer disease (AD). However, the pharmacological mechanism of butylphthalide from the brain network perspective is not clear. Therefore, we aimed to investigate the multimodal brain network changes associated with butylphthalide treatment in MCI due to AD. Methods A total of 270 patients with MCI due to AD received either butylphthalide or placebo at a ratio of 1:1 for 1 year. Effective treatment was defined as a decrease in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) > 2.5. Brain networks were constructed using T1-magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. A support vector machine was applied to develop predictive models. Results Both treatment (drug vs. placebo)-time interactions and efficacy (effective vs. ineffective)-time interactions were detected on some overlapping structural network metrics. Simple effects analyses revealed a significantly increased global efficiency in the structural network under both treatment and effective treatment of butylphthalide. Among the overlapping metrics, an increased degree centrality of left paracentral lobule was significantly related to poorer cognitive improvement. The predictive model based on baseline multimodal network metrics exhibited high accuracy (88.93%) of predicting butylphthalide's efficacy. Conclusion Butylphthalide may restore abnormal organization in structural networks of patients with MCI due to AD, and baseline network metrics could be predictive markers for therapeutic efficacy of butylphthalide. Clinical trial registration This study was registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR1800018362, Registration Date: 2018-09-13).
Key findings
- Therefore, we aimed to investigate the multimodal brain network changes associated with butylphthalide treatment in MCI due to AD.
- Results Both treatment (drug vs. placebo)-time interactions and efficacy (effective vs. ineffective)-time interactions were detected on some overlapping structural network metrics.
- Simple effects analyses revealed a significantly increased global efficiency in the structural network under both treatment and effective treatment of butylphthalide.
- Among the overlapping metrics, an increased degree centrality of left paracentral lobule was significantly related to poorer cognitive improvement.
Why it matters
In 270 people with mild cognitive impairment due to Alzheimer's disease, butylphthalide was linked to changes in brain network measures, with increased global efficiency in the structural network. This looks at brain network effects, not whether the drug prevents dementia or cures the disease.
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Study details
- Participants270
- Effect size88.93%
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Psychiatry and clinical neurosciences) |
| Journal's citation record | 1 / 4 | Psychiatry and Clinical Neurosciences: journal h-index 120 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 270 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Cuibai Wei: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40159989) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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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
Han, X., Gong, S., Gong, J., Wang, P., Li, R., Chen, R., et al. (2025). Structural and metabolic topological alterations associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, double-blind, placebo-controlled trial. Psychiatry and clinical neurosciences. https://doi.org/10.1111/pcn.13812
Vancouver
Han X, Gong S, Gong J, Wang P, Li R, Chen R, et al. Structural and metabolic topological alterations associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, double-blind, placebo-controlled trial. Psychiatry and clinical neurosciences. 2025. doi:10.1111/pcn.13812. PMID: 40159989.
BibTeX
@article{han2025-40159989,
author = {Han, X. and Gong, S. and Gong, J. and Wang, P. and Li, R. and Chen, R. and Xu, C. and Sun, W. and others},
title = {{Structural and metabolic topological alterations associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, double-blind, placebo-controlled trial}},
journal = {Psychiatry and clinical neurosciences},
year = {2025},
doi = {10.1111/pcn.13812},
pmid = {40159989},
url = {https://doi.org/10.1111/pcn.13812}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.