Home › Research › Long-term cohort studies
Stable brain architecture but flexible dynamics: distinct structure - function coupling signatures link aging and genetic Alzheimer's risk to cognitive decline in 34,067 adults
Zhang J, Wu X, Lian Z, Cheng Z, Peng S, Liu Y, Kuang N, Becker B et al.. Research Square, 2026-08-20
Topic: Brain imaging, connectivity and assessment
Understanding how a stable structural connectome supports flexible cognition, especially in aging, is a fundamental question in neuroscience. While static structure-function coupling (SFC) is well-studied, the temporal variability of structure-function coupling, referred to as dynamic SFC (DSFC), remains poorly characterized, particularly in relation to aging and cognitive outcomes. Leveraging MRI data from 34,067 UK Biobank participants (ages 45-82), we characterized the distinct roles of SFC and DSFC in aging, cognition, and health. We found that SFC and DSFC followed spatially divergent aging trajectories: SFC declined primarily in sensorimotor systems, whereas DSFC decreased most prominently in higher-order networks. Both SFC and DSFC in higher-order networks were positively correlated with cognitive performance (e.g., fluid intelligence). However, the associations with mental and physical health diverged spatially between the two measures: reduced DSFC was predominantly linked to health burden in high-order default/limbic networks, whereas weakened SFC was primarily associated with health burden in low-order sensory-motor networks. Genetic analyses revealed that Alzheimer's risk, specifically APOE ε4 dosage, significantly reduced DSFC in higher-order cognitive networks and SFC in low-order visual cortex. Mediation analyses further suggested that SFC and DSFC partially mediated the associations of aging and APOE ε4 dosage with cognitive performance. These findings suggest that static and dynamic coupling capture complementary aspects of brain organization: static SFC reflects the degree of functional alignment with structural architecture, whereas DSFC captures temporal variability in this alignment. Together, our results highlight these dual mechanisms as crucial for maintaining cognitive flexibility, providing potential biomarkers for age-related neurodegeneration.
Key findings
- We found that SFC and DSFC followed spatially divergent aging trajectories: SFC declined primarily in sensorimotor systems, whereas DSFC decreased most prominently in higher-order networks.
- However, the associations with mental and physical health diverged spatially between the two measures: reduced DSFC was predominantly linked to health burden in high-order default/limbic networks, whereas weakened SFC was primarily associated with health burden in low-order sensory-motor networks.
- Genetic analyses revealed that Alzheimer's risk, specifically APOE ε4 dosage, significantly reduced DSFC in higher-order cognitive networks and SFC in low-order visual cortex.
- Mediation analyses further suggested that SFC and DSFC partially mediated the associations of aging and APOE ε4 dosage with cognitive performance.
- These findings suggest that static and dynamic coupling capture complementary aspects of brain organization: static SFC reflects the degree of functional alignment with structural architecture, whereas DSFC captures temporal variability in this alignment.
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 (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 | 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. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Zhang, J., Wu, X., Lian, Z., Cheng, Z., Peng, S., Liu, Y., et al. (2026). Stable brain architecture but flexible dynamics: distinct structure - function coupling signatures link aging and genetic Alzheimer's risk to cognitive decline in 34,067 adults. Research Square. https://doi.org/10.21203/rs.3.rs-10563433/v1
Vancouver
Zhang J, Wu X, Lian Z, Cheng Z, Peng S, Liu Y, et al. Stable brain architecture but flexible dynamics: distinct structure - function coupling signatures link aging and genetic Alzheimer's risk to cognitive decline in 34,067 adults. Research Square. 2026. doi:10.21203/rs.3.rs-10563433/v1.
BibTeX
@article{zhang2026-c3c57035,
author = {Zhang, J. and Wu, X. and Lian, Z. and Cheng, Z. and Peng, S. and Liu, Y. and Kuang, N. and Becker, B. and others},
title = {{Stable brain architecture but flexible dynamics: distinct structure - function coupling signatures link aging and genetic Alzheimer's risk to cognitive decline in 34,067 adults}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10563433/v1},
url = {https://doi.org/10.21203/rs.3.rs-10563433/v1}
}