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Cerebral small vessel disease burden relates to cognitive decline via impaired amyloid clearance in the general population
C. Zhou, Fei Han, Feng Gao, Lu Zhou, Ming Yao, Jun Ni, Li-Ying Cui, Ming-Li Li et al.. Journal of Cerebral Blood Flow & Metabolism, 2026-04-10
Topic: Brain proteins, microglia and lab models
Our aim is to examine the interplay between cerebral small vessel disease (CSVD) pathology, Alzheimer’s disease (AD) related amyloid-β (Aβ) clearance, and cognition in general population. Cross-sectional structural equation modeling (SEM) was conducted to evaluate CSVD burden, cognition, and plasma Aβ42/40 ratios in 1026 participants without dementia from a prospective community-based cohort. CSVD burden was quantified using five established MRI markers, while cognition was assessed with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), verbal fluency test, and reverse digit span. Models were adjusted for age, sex, education, body mass index, vascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, and smoking), antihypertensive medication use, and APOE4 carrier status. Greater CSVD burden was significantly associated with poorer cognition ( B = −2.607 ± 1.016, β = −0.167, p = 0.010), with white matter hyperintensity volume (∆ R 2 = 0.3%, p = 0.016) and brain parenchymal fraction (∆ R 2 = 0.4%, p = 0.019) contributing most strongly. CSVD burden was also negatively correlated with plasma Aβ42/40 ratios ( B = −0.280 ± 0.074, β = −0.140, p < 0.001), which partially mediated the CSVD-cognition association ( B = −0.241 ± 0.087, β = −0.015, p = 0.006). These findings underscore potential CSVD involvement in AD-related pathology across aging.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhou, C., Han, F., Gao, F., Zhou, L., Yao, M., Ni, J., et al. (2026). Cerebral small vessel disease burden relates to cognitive decline via impaired amyloid clearance in the general population. Journal of Cerebral Blood Flow & Metabolism. https://doi.org/10.1177/0271678x261437577
Vancouver
Zhou C, Han F, Gao F, Zhou L, Yao M, Ni J, et al. Cerebral small vessel disease burden relates to cognitive decline via impaired amyloid clearance in the general population. Journal of Cerebral Blood Flow & Metabolism. 2026. doi:10.1177/0271678x261437577. PMID: 41958244.
BibTeX
@article{zhou2026-41958244,
author = {Zhou, C. and Han, Fei and Gao, Feng and Zhou, Lu and Yao, Ming and Ni, Jun and Cui, Li-Ying and Li, Ming-Li and others},
title = {{Cerebral small vessel disease burden relates to cognitive decline via impaired amyloid clearance in the general population}},
journal = {Journal of Cerebral Blood Flow \& Metabolism},
year = {2026},
doi = {10.1177/0271678x261437577},
pmid = {41958244},
url = {https://doi.org/10.1177/0271678x261437577}
}
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Key findings
- Greater CSVD burden was significantly associated with poorer cognition ( B = −2.607 ± 1.016, β = −0.167, p = 0.010), with white matter hyperintensity volume (∆ R 2 = 0.3%, p = 0.016) and brain parenchymal fraction (∆ R 2 = 0.4%, p = 0.019) contributing most strongly.
- These findings underscore potential CSVD involvement in AD-related pathology across aging.
Why it matters
In people without dementia, greater cerebral small vessel disease burden was associated with poorer cognition, and plasma amyloid-β42/40 ratios partially mediated this link. This suggests small vessel disease may contribute to Alzheimer's-related amyloid problems, but the cross-sectional design cannot prove that treating vascular disease would prevent dementia.
Study details
- Study designcross-sectional
- Participants1,026
- Effect size0.3%; 0.4%
- Evidence strengthModerate
How this study scored 52/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in 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 (Journal of Cerebral Blood Flow & Metabolism) |
| Journal's citation record | 3 / 4 | Journal of Cerebral Blood Flow & Metabolism: journal h-index 285 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,026 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 | 2 / 4 | Last-listed author Yi‐Cheng Zhu: h-index 46 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Science and Technology of China: institution h-index 1,001 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41958244) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
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