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Imaging brain fluid dynamics and waste clearance involving perivascular spaces in cerebral small vessel disease
Gemma Sole Guardia, Hao Li, Luc Willemse, Jessica Lebenberg, Éric Jouvent, Anil M. Tuladhar. Alzheimer s & Dementia, 2025-04-01
Topic: Brain proteins, microglia and lab models
Cerebral small vessel disease (SVD) is recognized as a major vascular contributor to cognitive decline, ultimately leading to dementia and stroke. While the pathogenesis of SVD remains unclear, emerging evidence suggests that waste clearance involving perivascular space (PVS) - also known as the glymphatic system - dysfunction may play a role. Among SVD radiological markers, the increased presence of dilated PVS is recognized as a marker of waste clearance disruption. Recently developed neuroimaging methods have been proposed as indirect measures of brain fluid dynamics, but they currently lack formal validation. Here, we provide a comprehensive overview of the latest neuroimaging advancements for assessing brain fluid dynamics, including waste clearance involving PVS function in SVD. We review the mechanisms by which clearance dysfunction might contribute to SVD. Finally, we argue that robust, multimodal, and longitudinal studies are essential for understanding the waste clearance (involving PVS) function and for establishing a diagnostic gold standard. HIGHLIGHTS: The majority of PVS are not visible on MRI, making it crucial to understand how and why they become dilated. The origin of waste clearance involving PVS disruption in SVD may be multifactorial. The BBB and waste clearance (involving PVS) dysfunction likely affect each other, forming a vicious cycle, promoting further amyloid beta accumulation. Yet their direct association in humans over time remains to be studied. Comparative studies can aid in the standardization of methods for assessing waste clearance involving PVS function.
Key findings
- While the pathogenesis of SVD remains unclear, emerging evidence suggests that waste clearance involving perivascular space (PVS) - also known as the glymphatic system - dysfunction may play a role.
Why it matters
This review discusses how dysfunction of waste clearance involving perivascular spaces may contribute to cerebral small vessel disease, and notes that current neuroimaging methods for measuring brain fluid dynamics lack formal validation. It calls for robust longitudinal studies and does not report any treatment, cure, or prevention for Alzheimer's disease.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 56/100
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 (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 7 | Cited 29 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Anil M. Tuladhar: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40289686) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Guardia, G. S., Li, H., Willemse, L., Lebenberg, J., Jouvent, É., & Tuladhar, A. M. (2025). Imaging brain fluid dynamics and waste clearance involving perivascular spaces in cerebral small vessel disease. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70212
Vancouver
Guardia GS, Li H, Willemse L, Lebenberg J, Jouvent É, Tuladhar AM. Imaging brain fluid dynamics and waste clearance involving perivascular spaces in cerebral small vessel disease. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70212. PMID: 40289686.
BibTeX
@article{guardia2025-40289686,
author = {Guardia, Gemma Sole and Li, Hao and Willemse, Luc and Lebenberg, Jessica and Jouvent, Éric and Tuladhar, Anil M.},
title = {{Imaging brain fluid dynamics and waste clearance involving perivascular spaces in cerebral small vessel disease}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70212},
pmid = {40289686},
url = {https://doi.org/10.1002/alz.70212}
}
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