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White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease
Soldan A, Pettigrew C, Zhu Y, Wang MC, Moghekar A, Gottesman RF, Singh B, Martinez O et al.. Neurology, 2019-12-30
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Objective Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and risk of progression from normal cognition to mild cognitive impairment (MCI). Methods Two sets of analyses were conducted. The relationship between whole brain WMH load, based on fluid-attenuated inversion recovery MRI, obtained in initially cognitively normal participants (n = 274) and time to onset of symptoms of MCI (n = 60) was examined using Cox regression models. In a subset of the participants with both MRI and CSF data (n = 204), the interaction of WMH load and CSF AD biomarkers was also evaluated. Results Baseline WMH load interacted with CSF total tau (t-tau) with respect to symptom onset, but not with CSF β-amyloid 1-42 or phosphorylated tau (p-tau) 181. WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau (hazard ratio [HR] 1.35, confidence interval [CI] 1.06-1.73, p = 0.013), but not those with high t-tau (HR 0.86, CI 0.56-1.32, p = 0.47). The rate of change in the CSF biomarkers over time was not associated with the rate of change in WMH volumes. Conclusion These results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to have largely independent and nonsynergistic effects on the risk of progression to MCI.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study of 274 participants. In 274 initially cognitively normal participants, baseline white matter hyperintensity load interacted with CSF total tau for time to symptom onset of mild cognitive impairment, with the association present only among those with low t-tau. Reported effect size: HR 0.86.
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
Soldan, A., Pettigrew, C., Zhu, Y., Wang, M. C., Moghekar, A., Gottesman, R. F., et al. (2020). White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000008864
Vancouver
Soldan A, Pettigrew C, Zhu Y, Wang MC, Moghekar A, Gottesman RF, et al. White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease. Neurology. 2020. doi:10.1212/wnl.0000000000008864. PMID: 31888969.
BibTeX
@article{soldan2020-31888969,
author = {Soldan, A. and Pettigrew, C. and Zhu, Y. and Wang, M. C. and Moghekar, A. and Gottesman, R. F. and Singh, B. and Martinez, O. and others},
title = {{White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease}},
journal = {Neurology},
year = {2020},
doi = {10.1212/wnl.0000000000008864},
pmid = {31888969},
url = {https://doi.org/10.1212/wnl.0000000000008864}
}
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Key findings
- Objective Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD).
- Results Baseline WMH load interacted with CSF total tau (t-tau) with respect to symptom onset, but not with CSF β-amyloid 1-42 or phosphorylated tau (p-tau) 181.
- WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau (hazard ratio [HR] 1.35, confidence interval [CI] 1.06-1.73, p = 0.013), but not those with high t-tau (HR 0.86, CI 0.56-1.32, p = 0.47).
- The rate of change in the CSF biomarkers over time was not associated with the rate of change in WMH volumes.
- Conclusion These results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low.
Why it matters
In 274 initially cognitively normal participants, baseline white matter hyperintensity load interacted with CSF total tau for time to symptom onset of mild cognitive impairment, with the association present only among those with low t-tau. This is an observational longitudinal finding about risk and does not show that treating white matter disease prevents Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Participants274
- Effect sizeHR 0.86
- Evidence strengthModerate
How this study scored 65/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 274 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 85 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 6.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Marilyn Albert: h-index 89 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31888969) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 100 | — |
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