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rTMS renews long-tract myelination to improve AD cognitive function predicted by baseline myelin and E-field
Zhu Z, Xu J, Wu N, Su Q, Zhu S, Jiang J, Zhang G, Wang L et al.. Research Square, 2026-09-25
Topic: Brain imaging, connectivity and assessment
Objective Alzheimer's disease (AD) is more than a neuronal disease, as myelin damage actively drives its pathogenesis. Maintaining myelin integrity during aging may delay the progression of AD. Myelin repair is an emerging strategy for AD treatment; however, whether rTMS can drive myelin remodeling through neuronal excitation remains unclear. Methods AD patients received rTMS targeting the left DLPFC. Myelin-sensitive white matter measures were assessed pre- and post-treatment. Functional connectivity (FC) changes within and between the cognitive networks were evaluated. Baseline myelin characteristics and individualized E-field modeling were used to predict clinical response. Results rTMS increased myelin content (MyC) in several left-hemisphere white matter tracts, particularly the superior fronto-occipital fasciculus (SFOF), superior corona radiata, and cingulum (Cohen’s d = 0.59 ,0.57, 0.59, separately). These changes were associated with enhanced CEN-SN cross-network, interhemispheric CEN, and intra-CEN connectivity enhancements, contributing to clinical improvement (correlations between MOCA and MyC of SFOF_L (R = 0.56, p < 0.01)). Baseline MyC of SFOF-L and E-field jointly predicted post-treatment cognitive outcomes, with the strongest MoCA model explaining 44.4% of the adjusted variance and outperformed either metric alone. No direct correlation was found between myelin increase and E-field, highlighting the constraining role of structural reserve. Conclusions This study reveals a myelin-mediated mechanism of rTMS action in AD, demonstrating the potential of promoting myelination as a novel therapeutic strategy for alleviating AD-related cognitive impairment. These findings support individualized biological dosing combining E-field modeling and myelin features of key tracts to identify the E-field threshold that triggers myelin remodeling, replacing traditional physical dose measures.
Key findings
- Results rTMS increased myelin content (MyC) in several left-hemisphere white matter tracts, particularly the superior fronto-occipital fasciculus (SFOF), superior corona radiata, and cingulum (Cohen’s d = 0.59 ,0.57, 0.59, separately).
- These changes were associated with enhanced CEN-SN cross-network, interhemispheric CEN, and intra-CEN connectivity enhancements, contributing to clinical improvement (correlations between MOCA and MyC of SFOF_L (R = 0.56, p < 0.01)).
- These findings support individualized biological dosing combining E-field modeling and myelin features of key tracts to identify the E-field threshold that triggers myelin remodeling, replacing traditional physical dose measures.
Study details
- Effect size44.4%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 15 of the 62 points we could judge it on, which is 24 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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APA 7th
Zhu, Z., Xu, J., Wu, N., Su, Q., Zhu, S., Jiang, J., et al. (2026). rTMS renews long-tract myelination to improve AD cognitive function predicted by baseline myelin and E-field. Research Square. https://doi.org/10.21203/rs.3.rs-10979108/v1
Vancouver
Zhu Z, Xu J, Wu N, Su Q, Zhu S, Jiang J, et al. rTMS renews long-tract myelination to improve AD cognitive function predicted by baseline myelin and E-field. Research Square. 2026. doi:10.21203/rs.3.rs-10979108/v1.
BibTeX
@article{zhu2026-b9daef42,
author = {Zhu, Z. and Xu, J. and Wu, N. and Su, Q. and Zhu, S. and Jiang, J. and Zhang, G. and Wang, L. and others},
title = {{rTMS renews long-tract myelination to improve AD cognitive function predicted by baseline myelin and E-field}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10979108/v1},
url = {https://doi.org/10.21203/rs.3.rs-10979108/v1}
}
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