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Inflammation and cerebral small vessel disease: A systematic review
Low A, Mak E, Rowe JB, Markus HS, O'Brien JT.. Ageing research reviews, 2019-06-10
Topic: Brain proteins, microglia and lab models
Inflammation is increasingly implicated as a risk factor for dementia, stroke, and small vessel disease (SVD). However, the underlying mechanisms and causative pathways remain unclear. We systematically reviewed the existing literature on the associations between markers of inflammation and SVD (i.e., white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMB)) in cohorts of older people with good health, cerebrovascular disease, or cognitive impairment. Based on distinctions made in the literature, markers of inflammation were classified as systemic inflammation (e.g. C-reactive protein, interleukin-6, fibrinogen) or vascular inflammation/endothelial dysfunction (e.g. homocysteine, von Willebrand factor, Lp-PLA2). Evidence from 82 articles revealed relatively robust associations between SVD and markers of vascular inflammation, especially amongst stroke patients, suggesting that alterations to the endothelium and blood-brain barrier may be a driving force behind SVD. Conversely, cross-sectional findings on systemic inflammation were mixed, although longitudinal investigations demonstrated that elevated levels of systemic inflammatory markers at baseline predicted subsequent SVD severity and progression. Importantly, regional analysis revealed that systemic and vascular inflammation were differentially related to two distinct forms of SVD. Specifically, markers of vascular inflammation tended to be associated with SVD in areas typical of hypertensive arteriopathy (e.g., basal ganglia), while systemic inflammation appeared to be involved in CAA-related vascular damage (e.g., centrum semiovale). Nonetheless, there is insufficient data to establish whether inflammation is causal of, or secondary to, SVD. Findings have important implications on interventions, suggesting the potential utility of treatments targeting the brain endothelium and blood brain barrier to combat SVD and associated neurodegenerative diseases.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Low, A., Mak, E., Rowe, J. B., Markus, H. S., & O'Brien, J. T. (2019). Inflammation and cerebral small vessel disease: A systematic review. Ageing research reviews. https://doi.org/10.1016/j.arr.2019.100916
Vancouver
Low A, Mak E, Rowe JB, Markus HS, O'Brien JT. Inflammation and cerebral small vessel disease: A systematic review. Ageing research reviews. 2019. doi:10.1016/j.arr.2019.100916. PMID: 31181331.
BibTeX
@article{low2019-31181331,
author = {Low, A. and Mak, E. and Rowe, J. B. and Markus, H. S. and O'Brien, J. T.},
title = {{Inflammation and cerebral small vessel disease: A systematic review}},
journal = {Ageing research reviews},
year = {2019},
doi = {10.1016/j.arr.2019.100916},
pmid = {31181331},
url = {https://doi.org/10.1016/j.arr.2019.100916}
}
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Key findings
- Evidence from 82 articles revealed relatively robust associations between SVD and markers of vascular inflammation, especially amongst stroke patients, suggesting that alterations to the endothelium and blood-brain barrier may be a driving force behind SVD.
- Conversely, cross-sectional findings on systemic inflammation were mixed, although longitudinal investigations demonstrated that elevated levels of systemic inflammatory markers at baseline predicted subsequent SVD severity and progression.
- Importantly, regional analysis revealed that systemic and vascular inflammation were differentially related to two distinct forms of SVD.
- Specifically, markers of vascular inflammation tended to be associated with SVD in areas typical of hypertensive arteriopathy (e.g., basal ganglia), while systemic inflammation appeared to be involved in CAA-related vascular damage (e.g., centrum semiovale).
Why it matters
This systematic review found links between small vessel disease in the brain and markers of vascular inflammation, especially in stroke patients, and that higher systemic inflammatory markers predicted later small vessel disease severity. It is about risk associations, not about treating or curing Alzheimer's disease.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 65/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Ageing research reviews) |
| Journal's citation record | 2 / 4 | Ageing Research Reviews: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question (from PubMed type “Systematic Review”) |
| 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 | 2 / 5 | 2019 — within 10 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 450 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 50.0 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 7.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 4 / 4 | Cited 233 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Tiernan O'Brien: h-index 140 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31181331) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 100 | — |
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