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Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia
Hainsworth AH, Minett T, Andoh J, Forster G, Bhide I, Barrick TR, Elderfield K, Jeevahan J et al.. Stroke, 2017-08-30
Topic: Brain proteins, microglia and lab models
Plain-language summary
Background and purpose We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Methods Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T 2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Results Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007). Conclusions Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.
What this study adds
Evidence grade: Low
The record lists 126 participants. In this postmortem study, the amount of fibrinogen labeling in subcortical white matter was not significantly linked to white matter abnormalities seen on MRI or under the microscope. Among people with normal MRI, more fibrinogen was linked to a lower risk of clinical dementia, but the study could not show a role for blood-brain barrier dysfunction in causing white matter damage.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Hainsworth, A. H., Minett, T., Andoh, J., Forster, G., Bhide, I., Barrick, T. R., et al. (2017). Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia. Stroke. https://doi.org/10.1161/strokeaha.117.018101
Vancouver
Hainsworth AH, Minett T, Andoh J, Forster G, Bhide I, Barrick TR, et al. Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia. Stroke. 2017. doi:10.1161/strokeaha.117.018101. PMID: 28855392.
BibTeX
@article{hainsworth2017-28855392,
author = {Hainsworth, A. H. and Minett, T. and Andoh, J. and Forster, G. and Bhide, I. and Barrick, T. R. and Elderfield, K. and Jeevahan, J. and others},
title = {{Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia}},
journal = {Stroke},
year = {2017},
doi = {10.1161/strokeaha.117.018101},
pmid = {28855392},
url = {https://doi.org/10.1161/strokeaha.117.018101}
}
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.
Key findings
- Background and purpose We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study).
- Results Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452).
- Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013).
- Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007).
- Conclusions Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.
Why it matters
In this postmortem study, the amount of fibrinogen labeling in subcortical white matter was not significantly linked to white matter abnormalities seen on MRI or under the microscope. Among people with normal MRI, more fibrinogen was linked to a lower risk of clinical dementia, but the study could not show a role for blood-brain barrier dysfunction in causing white matter damage.
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Study details
- Participants126
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stroke) |
| Journal's citation record | 3 / 4 | Stroke: journal h-index 455 (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 | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 126 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 95 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.6 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 5.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Leslie Bridges: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28855392) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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