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Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease
Wang T, Yan S, Shan Y, Xue H, Xing Y, Bi S, Chen Z, Xi H et al.. Radiology, 2025-06-01
Topic: Amyloid, tau and blood-test diagnosis
Background Transcranial alternating current stimulation (tACS) may be effective for improving cognitive function in Alzheimer disease (AD), but its impact on brain functional connectivity (FC) has not been well studied. Purpose To evaluate tACS efficacy in improving cognitive performance and modulating FC between brain regions in individuals with AD using functional MRI. Materials and Methods In this prospective randomized controlled trial (September 2020 to April 2022), participants with mild AD were assigned to active (40 Hz tACS with 15-mA intensity) or sham (no γ frequency or current) tACS groups for 3 weeks (referred to as week 3), with a 3-month follow-up (referred to as month 3). Functional MRI and cognitive testing were performed at baseline, week 3, and month 3. Primary outcomes were changes in Mini-Mental State Examination and Montreal Cognitive Assessment scores from baseline to week 3. Secondary outcomes included FC changes within multiple cortical networks and between cortex and hippocampus from baseline to week 3 and month 3, assessed using Fisher z -transformed correlation coefficient (hereafter, z score). Results Forty-six participants were randomized into the active group ( n = 23; median age, 66 years; IQR, 62-69 years; 16 female participants) or the sham group ( n = 23; mean age, 64 years; IQR, 61-69 years; 14 female participants). The active group had higher Mini-Mental State Examination (median score change, 2 [IQR, 1-5] vs 0 [IQR, -1 to 2]; P = .001) and Montreal Cognitive Assessment (median score change, 2 [IQR, 0-4] vs 0 [IQR, -1 to 2]; P = .03) scores than the sham group at week 3, respectively. Compared with the sham group, the active group had increased FC between left hippocampus and left middle cingulate gyrus ( z score difference, 0.29; 95% CI: 0.17, 0.42; false discovery rate [FDR]-adjusted P z score difference, 0.16; 95% CI: 0.03, 0.29; FDR-adjusted P = .04) within the posterior default-mode network ( z score difference, 0.40; 95% CI: 0.07, 0.73; FDR-adjusted P = .046) and within the visual network ( z score difference, 0.45; 95% CI: 0.17, 0.73; FDR-adjusted P = .007) from baseline to week 3. Conclusion Cognitive performance in mild AD improved following tACS, with increased FC within cortical networks and between the hippocampus and specific cortical regions. ClinicalTrials.gov Identifier: NCT03920826 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, T., Yan, S., Shan, Y., Xue, H., Xing, Y., Bi, S., et al. (2025). Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease. Radiology. https://doi.org/10.1148/radiol.241463
Vancouver
Wang T, Yan S, Shan Y, Xue H, Xing Y, Bi S, et al. Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease. Radiology. 2025. doi:10.1148/radiol.241463. PMID: 40552996.
BibTeX
@article{wang2025-40552996,
author = {Wang, T. and Yan, S. and Shan, Y. and Xue, H. and Xing, Y. and Bi, S. and Chen, Z. and Xi, H. and others},
title = {{Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease}},
journal = {Radiology},
year = {2025},
doi = {10.1148/radiol.241463},
pmid = {40552996},
url = {https://doi.org/10.1148/radiol.241463}
}
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Key findings
- Results Forty-six participants were randomized into the active group ( n = 23; median age, 66 years; IQR, 62-69 years; 16 female participants) or the sham group ( n = 23; mean age, 64 years; IQR, 61-69 years; 14 female participants).
- Compared with the sham group, the active group had increased FC between left hippocampus and left middle cingulate gyrus ( z score difference, 0.29; 95% CI: 0.17, 0.42; false discovery rate [FDR]-adjusted P < .001) and between the left hippocampus and the left middle frontal gyrus ( z score difference, 0.16; 95% CI: 0.03, 0.29; FDR-adjusted P = .04) within the posterior default-mode network ( z score difference, 0.40; 95% CI: 0.07, 0.73; FDR-adjusted P = .046) and within the visual network ( z score difference, 0.45; 95% CI: 0.17, 0.73; FDR-adjusted P = .007) from baseline to week 3.
Why it matters
In a randomized trial of 46 people with mild Alzheimer disease, active transcranial alternating current stimulation increased functional connectivity between the left hippocampus and left middle cingulate gyrus compared with sham. This is a small, early study of brain connectivity changes, not proof of cognitive benefit.
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Study details
- Study designrandomized controlled trial
- Participants23
- Evidence strengthHigh
How this study scored 61/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 59 of the 96 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Radiology) |
| Journal's citation record | 3 / 4 | Radiology: journal h-index 431 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 1 / 4 | 23 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40552996) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 59 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 96 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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