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Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer’s disease
Si Cen, Lijuan Wang, Meiling Qiu, Zhongqiang Xu, Li Xu, Rui Bao, Xiaolei Tang, Juanyu Gong et al.. The Journal of Prevention of Alzheimer s Disease, 2025-07-29
Topic: Brain proteins, microglia and lab models
Progressive cortical thinning in multiple cognition-related regions was significantly associated with cBF atrophy. Mediation analysis revealed that cortical thinning accounted for approximately 44 % of the relationship between cBF degeneration and cognitive decline. These associations were more pronounced in individuals with elevated Aβ, suggesting a synergistic interaction between amyloid pathology and cholinergic system degeneration. Our findings suggest that cBF atrophy accelerates cognitive decline through its impact on cortical thinning, with Aβ pathology further exacerbating these effects. These results highlight the potential of cBF and cortical thinning as early biomarkers for preclinical AD and underscore the importance of targeting cholinergic dysfunction in early intervention strategies.
Key findings
- Progressive cortical thinning in multiple cognition-related regions was significantly associated with cBF atrophy.
- Mediation analysis revealed that cortical thinning accounted for approximately 44 % of the relationship between cBF degeneration and cognitive decline.
- These associations were more pronounced in individuals with elevated Aβ, suggesting a synergistic interaction between amyloid pathology and cholinergic system degeneration.
- Our findings suggest that cBF atrophy accelerates cognitive decline through its impact on cortical thinning, with Aβ pathology further exacerbating these effects.
- These results highlight the potential of cBF and cortical thinning as early biomarkers for preclinical AD and underscore the importance of targeting cholinergic dysfunction in early intervention strategies.
Why it matters
This longitudinal study found that cholinergic basal forebrain atrophy was associated with cortical thinning, which accounted for about 44% of the relationship between basal forebrain degeneration and cognitive decline, with stronger effects in people with elevated amyloid-β. The authors suggest basal forebrain and cortical thinning as early biomarkers and highlight targeting cholinergic dysfunction in early intervention strategies, but no treatment or cure was tested.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 45/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| 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 | 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 | 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 | 2 / 7 | Cited 12 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.6× 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 | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Wencai Ding: h-index 8 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | First Affiliated Hospital of Harbin Medical University: institution h-index 228 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40731233) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100315
- PubMed: 40731233
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s 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. 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
Cen, S., Wang, L., Qiu, M., Xu, Z., Xu, L., Bao, R., et al. (2025). Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer’s disease. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2025.100315
Vancouver
Cen S, Wang L, Qiu M, Xu Z, Xu L, Bao R, et al. Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer’s disease. The Journal of Prevention of Alzheimer s Disease. 2025. doi:10.1016/j.tjpad.2025.100315. PMID: 40731233.
BibTeX
@article{cen2025-40731233,
author = {Cen, Si and Wang, Lijuan and Qiu, Meiling and Xu, Zhongqiang and Xu, Li and Bao, Rui and Tang, Xiaolei and Gong, Juanyu and others},
title = {{Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer’s disease}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100315},
pmid = {40731233},
url = {https://doi.org/10.1016/j.tjpad.2025.100315}
}
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