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CSF Biomarker‐Based Cognitive Trajectories in Parkinson's Disease‐Subjective Cognitive Decline
Jon Rodriguez‐Antiguedad, Arnau Puig‐Davi, Iñigo Ruíz‐Barrio, Javier Pagonabarraga, Anna Vázquez‐Oliver, Andrea Horta‐Barba, Jaime Kulisevsky, Saül Martínez‐Horta. Annals of Clinical and Translational Neurology, 2025-06-11
Topic: Risk, prevention and care in population studies
ABSTRACT Objective Cognitive complaints without objective cognitive impairment in Parkinson's Disease, termed Parkinson's Disease‐Subjective Cognitive Decline (PD‐SCD), have been associated with cognitive decline. However, its progression is heterogeneous, highlighting the need for improved identification of patients at greater risk for deterioration. This cohort study aims to investigate associations between CSF biomarkers and cognitive decline in PD‐SCD. Methods We included patients from the PPMI cohort with PD‐SCD, available baseline CSF beta‐amyloid1‐42 (Aβ42) and phosphorylated‐tau181 (p‐tau181), and longitudinal Montreal Cognitive Assessment (MoCA). Results A total of 80 patients were included, with a mean age of 62.1 years and a median disease duration of 5.6 months at baseline. Five patients were identified with biological AD, who showed a more pronounced decline in MoCA (year 7: β = −4.15, p = 0.009). After excluding AD patients, linear mixed‐effects models (LMEM) demonstrated an association between baseline log‐transformed Aβ42 and MoCA progression (β = 2, p = 0.004). Based on these data, we created three CSF‐based subgroups: Normal Aβ42 (n = 50), Low Aβ42 (n = 25), and Biological AD (n = 5). LMEM predicted greater cognitive decline for Low Aβ42 versus Normal Aβ42 (β = −0.161 points‐per‐year, p = 0.007), and for Biological AD versus Normal Aβ42 (β = −0.390 points‐per‐year, p < 0.001). The risk of dementia was increased for Low Aβ42 (HR = 5.2, p = 0.029) and Biological AD subgroups (HR = 7.7, p = 0.013). Interpretation In PD‐SCD, baseline CSF Aβ42 is associated with cognitive progression. Furthermore, we identified three CSF biomarker‐based cognitive trajectories (Normal Aβ42, Low Aβ42, and Biological AD), each characterized by progressively worse cognitive outcomes. These findings could be useful for implementing enrichment strategies in future clinical trials targeting PD‐associated cognitive decline.
Key findings
- ABSTRACT Objective Cognitive complaints without objective cognitive impairment in Parkinson's Disease, termed Parkinson's Disease‐Subjective Cognitive Decline (PD‐SCD), have been associated with cognitive decline.
- Results A total of 80 patients were included, with a mean age of 62.1 years and a median disease duration of 5.6 months at baseline.
- After excluding AD patients, linear mixed‐effects models (LMEM) demonstrated an association between baseline log‐transformed Aβ42 and MoCA progression (β = 2, p = 0.004).
- LMEM predicted greater cognitive decline for Low Aβ42 versus Normal Aβ42 (β = −0.161 points‐per‐year, p = 0.007), and for Biological AD versus Normal Aβ42 (β = −0.390 points‐per‐year, p < 0.001).
- Interpretation In PD‐SCD, baseline CSF Aβ42 is associated with cognitive progression.
Why it matters
In 80 patients with Parkinson's disease and subjective cognitive decline, this cohort study found that those with low CSF Aβ42 or biological Alzheimer's disease showed greater cognitive decline over time. The findings suggest CSF biomarkers can help identify Parkinson's patients at higher risk of cognitive deterioration, but the study does not test any treatment.
Study details
- Study designcohort study
- Participants50
- Effect sizeHR = 5.2; HR = 7.7
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Annals of Clinical and Translational Neurology) |
| Journal's citation record | 1 / 4 | Annals of Clinical and Translational Neurology: journal h-index 97 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 50 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Saül Martínez‐Horta: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40501082) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/acn3.70075
- PubMed: 40501082
- Original source →
- Free full text: Annals of Clinical and Translational Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Rodriguez‐Antiguedad, J., Puig‐Davi, A., Ruíz‐Barrio, I., Pagonabarraga, J., Vázquez‐Oliver, A., Horta‐Barba, A., et al. (2025). CSF Biomarker‐Based Cognitive Trajectories in Parkinson's Disease‐Subjective Cognitive Decline. Annals of Clinical and Translational Neurology. https://doi.org/10.1002/acn3.70075
Vancouver
Rodriguez‐Antiguedad J, Puig‐Davi A, Ruíz‐Barrio I, Pagonabarraga J, Vázquez‐Oliver A, Horta‐Barba A, et al. CSF Biomarker‐Based Cognitive Trajectories in Parkinson's Disease‐Subjective Cognitive Decline. Annals of Clinical and Translational Neurology. 2025. doi:10.1002/acn3.70075. PMID: 40501082.
BibTeX
@article{rodriguezantiguedad2025-40501082,
author = {Rodriguez‐Antiguedad, Jon and Puig‐Davi, Arnau and Ruíz‐Barrio, Iñigo and Pagonabarraga, Javier and Vázquez‐Oliver, Anna and Horta‐Barba, Andrea and Kulisevsky, Jaime and Martínez‐Horta, Saül},
title = {{CSF Biomarker‐Based Cognitive Trajectories in Parkinson's Disease‐Subjective Cognitive Decline}},
journal = {Annals of Clinical and Translational Neurology},
year = {2025},
doi = {10.1002/acn3.70075},
pmid = {40501082},
url = {https://doi.org/10.1002/acn3.70075}
}
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