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White matter hyperintensities: relationship to amyloid and tau burden
Graff-Radford J, Arenaza-Urquijo EM, Knopman DS, Schwarz CG, Brown RD, Rabinstein AA, Gunter JL, Senjem ML et al.. Brain : a journal of neurology, 2019-08-01
Topic: Brain proteins, microglia and lab models
Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer's disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer's disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2* gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer's biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen's d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.
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APA 7th
Graff-Radford, J., Arenaza-Urquijo, E. M., Knopman, D. S., Schwarz, C. G., Brown, R. D., Rabinstein, A. A., et al. (2019). White matter hyperintensities: relationship to amyloid and tau burden. Brain : a journal of neurology. https://doi.org/10.1093/brain/awz162
Vancouver
Graff-Radford J, Arenaza-Urquijo EM, Knopman DS, Schwarz CG, Brown RD, Rabinstein AA, et al. White matter hyperintensities: relationship to amyloid and tau burden. Brain : a journal of neurology. 2019. doi:10.1093/brain/awz162. PMID: 31199475.
BibTeX
@article{graffradford2019-31199475,
author = {Graff-Radford, J. and Arenaza-Urquijo, E. M. and Knopman, D. S. and Schwarz, C. G. and Brown, R. D. and Rabinstein, A. A. and Gunter, J. L. and Senjem, M. L. and others},
title = {{White matter hyperintensities: relationship to amyloid and tau burden}},
journal = {Brain : a journal of neurology},
year = {2019},
doi = {10.1093/brain/awz162},
pmid = {31199475},
url = {https://doi.org/10.1093/brain/awz162}
}
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
- The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer's disease biomarkers measured using PET.
- We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer's biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension.
- In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis.
- Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities.
Why it matters
In 434 participants without dementia, this study examined which white matter hyperintensity regions on MRI were associated with amyloid and tau on PET. It is an imaging association study and does not test any treatment, cure or prevention.
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Study details
- Participants434
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 434 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 257 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.6 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 19.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 111 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Prashanthi Vemuri: h-index 106 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (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 31199475) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
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