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White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status
Kern KC, Vohra M, Thirion ML, Wang DJJ, Wilcock DM, Thompson JF, Rosenberg GA, Sagare A et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-12-18
Topic: Brain proteins, microglia and lab models
Plain-language summary
Introduction Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment. Methods MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included. We tested cross-sectionally whether FW mediated the associations between PlGF and WMH, or PlGF and cognition, measured using the Clinical Dementia Rating (CDR) scale and an executive function (EF) composite (Uniform Data Set version 3 [UDS3]-EF). Results For 370 participants (mean age 72), a higher PlGF was associated with higher FW, higher WMH, and higher CDR, but not UDS3-EF. Higher FW was associated with higher WMH, higher CDR, and lower UDS3-EF. FW explained 26% of the association between PlGF and CDR and 73% of the association between PlGF and WMH. Discussion Elevated PlGF may contribute to WMH and cognitive impairment through white matter FW accumulation. Clinical trial registration NCT06284213 HIGHLIGHTS: PlGF is a promising blood-based biomarker for vascular cognitive impairment. In MarkVCID, higher PlGF was associated with accumulated white matter FW on MRI. FW mediated the association between higher PlGF and MRI-visible white matter injury. FW mediated the association between PlGF and worse CDR scale. PlGF may contribute to cognitive dysfunction via accumulated interstitial fluid.
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APA 7th
Kern, K. C., Vohra, M., Thirion, M. L., Wang, D. J. J., Wilcock, D. M., Thompson, J. F., et al. (2025). White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14408
Vancouver
Kern KC, Vohra M, Thirion ML, Wang DJJ, Wilcock DM, Thompson JF, et al. White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.14408. PMID: 39692213.
BibTeX
@article{kern2025-39692213,
author = {Kern, K. C. and Vohra, M. and Thirion, M. L. and Wang, D. J. J. and Wilcock, D. M. and Thompson, J. F. and Rosenberg, G. A. and Sagare, A. and others},
title = {{White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.14408},
pmid = {39692213},
url = {https://doi.org/10.1002/alz.14408}
}
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Key findings
- Results For 370 participants (mean age 72), a higher PlGF was associated with higher FW, higher WMH, and higher CDR, but not UDS3-EF.
- Higher FW was associated with higher WMH, higher CDR, and lower UDS3-EF.
- In MarkVCID, higher PlGF was associated with accumulated white matter FW on MRI.
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Study details
- Participants370
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 370 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39692213) |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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