Turbulent dynamics and in silico perturbation-based measures are disrupted across biological stages of Alzheimers disease
Martinez-Molina N, Aquilue-Llorens D, Rass L, Montana-Valverde G, Patow G, Escrichs A, Sanz-Perl Y, Kringelbach ML et al.. medRxiv, 2026-10-13
Topic: Brain imaging, connectivity and assessment
According to the AT(N) framework, Alzheimers disease (AD) can be biologically characterised by amyloid deposition, tau pathology, and neurodegeneration, yet how these processes relate to whole-brain dynamics remains unclear. Here, we investigated these relationships and the link between whole-brain dynamics and cognitive dysfunction using multimodal neuroimaging from 145 ADNI3 participants. We combined multiscale measures of turbulent dynamics with responses to in silico perturbations obtained from whole-brain models. AD progression was characterised by a scale-dependent reorganisation of turbulent dynamics where information flow showed the strongest contribution to the dynamics-related variance in cognitive performance. Large-scale turbulence was associated with all three AT(N) components. Model-based information capability and susceptibility measures progressively decreased across AD stages and were associated with amyloid burden and regional tau deposition. Model-free features discriminated comparisons involving AD dementia, whereas adding model-based measures produced modest, metric-dependent changes in classification performance. Exploratory analyses showed spatial alignment between large-scale turbulence alterations and AD-risk gene-expression gradients, with APOE among the strongest associations in both disease-stage contrasts examined. Lastly, we found a progressive decoupling between turbulent dynamics and the E:I balance across AD stages. Together, these findings link model-based and model-free measures of whole-brain dynamics to proteinopathy, neurodegeneration, and cognitive impairment, supporting their complementary value for characterising AD progression.
Key findings
- Large-scale turbulence was associated with all three AT(N) components.
- Model-based information capability and susceptibility measures progressively decreased across AD stages and were associated with amyloid burden and regional tau deposition.
- Lastly, we found a progressive decoupling between turbulent dynamics and the E:I balance across AD stages.
- Together, these findings link model-based and model-free measures of whole-brain dynamics to proteinopathy, neurodegeneration, and cognitive impairment, supporting their complementary value for characterising AD progression.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 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, effect reported, 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| 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 | 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 | — / 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 | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Martinez-Molina, N., Aquilue-Llorens, D., Rass, L., Montana-Valverde, G., Patow, G., Escrichs, A., et al. (2026). Turbulent dynamics and in silico perturbation-based measures are disrupted across biological stages of Alzheimers disease. medRxiv. https://doi.org/10.64898/2026.10.12.26365318
Vancouver
Martinez-Molina N, Aquilue-Llorens D, Rass L, Montana-Valverde G, Patow G, Escrichs A, et al. Turbulent dynamics and in silico perturbation-based measures are disrupted across biological stages of Alzheimers disease. medRxiv. 2026. doi:10.64898/2026.10.12.26365318.
BibTeX
@article{martinezmolina2026-3a38ca44,
author = {Martinez-Molina, N. and Aquilue-Llorens, D. and Rass, L. and Montana-Valverde, G. and Patow, G. and Escrichs, A. and Sanz-Perl, Y. and Kringelbach, M. L. and others},
title = {{Turbulent dynamics and in silico perturbation-based measures are disrupted across biological stages of Alzheimers disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.12.26365318},
url = {https://doi.org/10.64898/2026.10.12.26365318}
}
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