Home › Research › Mild cognitive impairment
Characterizing the distinct neuroanatomical phenotypes, cognitive profiles, and transcriptomic signatures of brain structural subtypes in Parkinson's disease with mild cognitive impairment
Lei Yan, Jingru Ren, Hao Zhou, Yi Xing, Shuoying Chen, WeiGuo Liu. Neurobiology of Disease, 2025-10-15
Topic: Brain proteins, microglia and lab models
Two distinct subtypes emerged. Subtype 1 (n = 63) features localized supra-normal gray matter volume deviations in dorsolateral prefrontal regions, elevated free water indicating microstructural disruption, executive dysfunction, and transcriptional enrichment in metabolic dysfunction and neurodegenerative pathways. Subtype 2 (n = 41) displays widespread infra-normal gray matter volume deviations across cortical-limbic areas. Microstructural integrity is preserved despite volumetric reduction, reflecting successful adaptive compensation. Cognitive network connectivity is enhanced (density: 0.95 vs 0.90). Molecular signatures occur in cellular organization and signal transduction pathways. Subtypes show distinct vulnerability patterns in frontal-executive versus limbic-memory networks. External validation in an independent PPMI cohort (n = 115) confirms the two-subtype structure, with consistent reproduction of the fundamental degenerative-adaptive dichotomy despite some regional variability in the validation cohort. Study findings provide evidence that PD-MCI encompasses biologically distinct subtypes. These subtypes have divergent neuroanatomical patterns, microstructural properties, cognitive profiles, and molecular mechanisms. Multimodal approach reveals fundamental disease heterogeneity and establishes a framework for precision medicine in Parkinson's disease cognitive impairment. Sex-specific distribution across subtypes indicates biological sex should be considered an integral component of PD-MCI heterogeneity rather than a confounding factor. This distribution has important implications for developing sex-specific therapeutic strategies.
Key findings
- Subtype 1 (n = 63) features localized supra-normal gray matter volume deviations in dorsolateral prefrontal regions, elevated free water indicating microstructural disruption, executive dysfunction, and transcriptional enrichment in metabolic dysfunction and neurodegenerative pathways.
- Subtype 2 (n = 41) displays widespread infra-normal gray matter volume deviations across cortical-limbic areas.
- Microstructural integrity is preserved despite volumetric reduction, reflecting successful adaptive compensation.
- Cognitive network connectivity is enhanced (density: 0.95 vs 0.90).
- Molecular signatures occur in cellular organization and signal transduction pathways.
Why it matters
This study identified two brain structural subtypes in Parkinson's disease with mild cognitive impairment, one with executive dysfunction and metabolic and neurodegenerative pathway changes, and another with preserved microstructure and enhanced cognitive network connectivity. It is about Parkinson's disease cognitive impairment, not Alzheimer's disease treatment or cure, and it suggests these subtypes may support precision medicine approaches.
Study details
- Participants115
- Evidence strengthModerate
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 38 of the 96 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of Disease) |
| Journal's citation record | 2 / 4 | Neurobiology of Disease: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2 / 4 | 115 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× 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 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 0 / 3 | Nanjing Medical University: institution h-index 508 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41101651) |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 38 of the 96 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.nbd.2025.107141
- PubMed: 41101651
- Original source →
- Free full text: Neurobiology of Disease →
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. Check the citation against the original before you use it.
APA 7th
Yan, L., Ren, J., Zhou, H., Xing, Y., Chen, S., & Liu, W. (2025). Characterizing the distinct neuroanatomical phenotypes, cognitive profiles, and transcriptomic signatures of brain structural subtypes in Parkinson's disease with mild cognitive impairment. Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2025.107141
Vancouver
Yan L, Ren J, Zhou H, Xing Y, Chen S, Liu W. Characterizing the distinct neuroanatomical phenotypes, cognitive profiles, and transcriptomic signatures of brain structural subtypes in Parkinson's disease with mild cognitive impairment. Neurobiology of Disease. 2025. doi:10.1016/j.nbd.2025.107141. PMID: 41101651.
BibTeX
@article{yan2025-41101651,
author = {Yan, Lei and Ren, Jingru and Zhou, Hao and Xing, Yi and Chen, Shuoying and Liu, WeiGuo},
title = {{Characterizing the distinct neuroanatomical phenotypes, cognitive profiles, and transcriptomic signatures of brain structural subtypes in Parkinson's disease with mild cognitive impairment}},
journal = {Neurobiology of Disease},
year = {2025},
doi = {10.1016/j.nbd.2025.107141},
pmid = {41101651},
url = {https://doi.org/10.1016/j.nbd.2025.107141}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.