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Pre-dementia clinical trajectories associated with neuronal α-synuclein neuropathologic change: a retrospective cohort study
Illán-Gala I, Vera E, Selma-González J, Rodríguez-Baz Í, Abdelnour C, Rodriguez-Porcel F, Wyman-Chick K, Toledo J et al.. Research Square, 2026-08-27
Topic: Plasma and spinal-fluid biomarkers
Biological definitions of neuronal α-synuclein disease are advancing diagnosis beyond traditional clinical syndromes, but the trajectories preceding dementia and the influence of concomitant Alzheimer pathology remain uncertain. We analyzed longitudinal data from 1,543 participants without dementia at baseline who underwent repeated cognitive, functional, neuropsychiatric, and motor assessments and had neuropathological characterization at autopsy. Participants were classified as having neuronal α-synuclein neuropathologic change (NSNC), Alzheimer’s disease neuropathologic change (ADNC), or both. NSNC without intermediate or high ADNC was associated with the greatest motor burden. Among participants without mild cognitive impairment at baseline, concomitant ADNC was associated with earlier cognitive impairment and faster cognitive decline; mixed NSNC/ADNC also showed faster functional worsening than NSNC alone. Across participants with NSNC, baseline mild cognitive impairment, neuropsychiatric manifestations and concomitant ADNC predicted progression to dementia, whereas prespecified motor signs did not. These findings reveal heterogeneous pre-dementia trajectories and support combining α-synuclein detection with Alzheimer biomarkers, cognitive staging and multidomain clinical measures to improve prognosis and trial design.
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APA 7th
Illán-Gala, I., Vera, E., Selma-González, J., Í, R.-B., Abdelnour, C., Rodriguez-Porcel, F., et al. (2026). Pre-dementia clinical trajectories associated with neuronal α-synuclein neuropathologic change: a retrospective cohort study. Research Square. https://doi.org/10.21203/rs.3.rs-10788306/v1
Vancouver
Illán-Gala I, Vera E, Selma-González J, Í R.-B, Abdelnour C, Rodriguez-Porcel F, et al. Pre-dementia clinical trajectories associated with neuronal α-synuclein neuropathologic change: a retrospective cohort study. Research Square. 2026. doi:10.21203/rs.3.rs-10788306/v1.
BibTeX
@article{illangala2026-434cc4bc,
author = {Illán-Gala, I. and Vera, E. and Selma-González, J. and Í, Rodríguez-Baz and Abdelnour, C. and Rodriguez-Porcel, F. and Wyman-Chick, K. and Toledo, J. and others},
title = {{Pre-dementia clinical trajectories associated with neuronal α-synuclein neuropathologic change: a retrospective cohort study}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10788306/v1},
url = {https://doi.org/10.21203/rs.3.rs-10788306/v1}
}
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Key findings
- NSNC without intermediate or high ADNC was associated with the greatest motor burden.
- Among participants without mild cognitive impairment at baseline, concomitant ADNC was associated with earlier cognitive impairment and faster cognitive decline; mixed NSNC/ADNC also showed faster functional worsening than NSNC alone.
- These findings reveal heterogeneous pre-dementia trajectories and support combining α-synuclein detection with Alzheimer biomarkers, cognitive staging and multidomain clinical measures to improve prognosis and trial design.
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Study details
- Study designlongitudinal study
- Participants1,543
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 45 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported 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 28 of the 62 points we could judge it on, which is 45 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 | 3 / 4 | 1,543 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 | 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 | 28 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 28 of the 62 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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