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Neuropathologic basis of white matter hyperintensity accumulation with advanced age
Erten-Lyons D, Woltjer R, Kaye J, Mattek N, Dodge HH, Green S, Tran H, Howieson DB et al.. Neurology, 2013-08-09
Topic: Brain proteins, microglia and lab models
Objective To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. Methods Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p Results Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). Conclusion Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.
Key findings
- A final model included measures showing an association with p Results Mean age at death was 94.5 years (5.5 SD).
- In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time.
- In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003).
- Additionally, these results suggest a link between AD pathology and white matter integrity disruption.
Why it matters
In 66 older people with autopsy and more than one MRI, arteriolosclerosis, myelin pallor, and higher Braak score were associated with greater white matter hyperintensity accumulation over time. The authors suggest these changes are likely driven by small-vessel disease, but this is a pathology correlation study with no treatment tested.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 58/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / 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 | 1 / 5 | 2013 — within 20 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 224 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.9 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 10.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 2 / 4 | Cited 39 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lisa C. Silbert: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Oregon Health & Science University: institution h-index 1,025 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23935177) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Erten-Lyons, D., Woltjer, R., Kaye, J., Mattek, N., Dodge, H. H., Green, S., et al. (2013). Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology. https://doi.org/10.1212/wnl.0b013e3182a43e45
Vancouver
Erten-Lyons D, Woltjer R, Kaye J, Mattek N, Dodge HH, Green S, et al. Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology. 2013. doi:10.1212/wnl.0b013e3182a43e45. PMID: 23935177.
BibTeX
@article{ertenlyons2013-23935177,
author = {Erten-Lyons, D. and Woltjer, R. and Kaye, J. and Mattek, N. and Dodge, H. H. and Green, S. and Tran, H. and Howieson, D. B. and others},
title = {{Neuropathologic basis of white matter hyperintensity accumulation with advanced age}},
journal = {Neurology},
year = {2013},
doi = {10.1212/wnl.0b013e3182a43e45},
pmid = {23935177},
url = {https://doi.org/10.1212/wnl.0b013e3182a43e45}
}
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