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Network-level functional connectivity is associated with longitudinal tau accumulation and amyloid-dependent cognitive decline in preclinical Alzheimer’s disease
Javanray M, Gallego-Rudolf J, Yakoub Y, Qiu T, St-Onge F, Remz J, Soucy J, Misic B et al.. Research Square, 2026-08-25
Topic: Brain imaging, connectivity and assessment
Amyloid-β and tau, pathological hallmarks of AD, silently accumulate years before clinical symptoms’ onset and are associated with neuronal dysfunction and cognitive impairment. Although functional connectivity has shown promise in tracking AD proteinopathy, how large-scale brain functional connections and their temporal variability relate to longitudinal pathological and cognitive changes during the preclinical stage remains unclear. Here, we examined both static and time-varying functional connectivity across brain networks in cognitively unimpaired older adults with a family history of AD, who underwent resting-state fMRI, longitudinal amyloid- and tau-PET imaging, and decade-long neuropsychological assessments. We found that lower static connectivity across multiple large-scale networks was associated with faster longitudinal tau accumulation and, selectively in individuals with elevated amyloid burden, with accelerated cognitive decline. These associations were not observed for time-varying connectivity. Together, our results demonstrate a role of static functional network organization in early pathological and cognitive progression of AD.
Key findings
- Amyloid-β and tau, pathological hallmarks of AD, silently accumulate years before clinical symptoms’ onset and are associated with neuronal dysfunction and cognitive impairment.
- We found that lower static connectivity across multiple large-scale networks was associated with faster longitudinal tau accumulation and, selectively in individuals with elevated amyloid burden, with accelerated cognitive decline.
- Together, our results demonstrate a role of static functional network organization in early pathological and cognitive progression of AD.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for 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 22 of the 62 points we could judge it on, which is 35 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 | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 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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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
Javanray, M., Gallego-Rudolf, J., Yakoub, Y., Qiu, T., St-Onge, F., Remz, J., et al. (2026). Network-level functional connectivity is associated with longitudinal tau accumulation and amyloid-dependent cognitive decline in preclinical Alzheimer’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-10282950/v1
Vancouver
Javanray M, Gallego-Rudolf J, Yakoub Y, Qiu T, St-Onge F, Remz J, et al. Network-level functional connectivity is associated with longitudinal tau accumulation and amyloid-dependent cognitive decline in preclinical Alzheimer’s disease. Research Square. 2026. doi:10.21203/rs.3.rs-10282950/v1.
BibTeX
@article{javanray2026-8250ae3c,
author = {Javanray, M. and Gallego-Rudolf, J. and Yakoub, Y. and Qiu, T. and St-Onge, F. and Remz, J. and Soucy, J. and Misic, B. and others},
title = {{Network-level functional connectivity is associated with longitudinal tau accumulation and amyloid-dependent cognitive decline in preclinical Alzheimer’s disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10282950/v1},
url = {https://doi.org/10.21203/rs.3.rs-10282950/v1}
}
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