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Trajectory of white matter hyperintensity burden preceding mild cognitive impairment
Silbert LC, Dodge HH, Perkins LG, Sherbakov L, Lahna D, Erten-Lyons D, Woltjer R, Shinto L et al.. Neurology, 2012-07-25
Topic: Risk, prevention and care in population studies
Objective To determine the time of acceleration in white matter hyperintensity (WMH) burden, a common indicator of cerebrovascular pathology, in relation to conversion to mild cognitive impairment (MCI) in the elderly. Methods A total of 181 cognitively intact elderly volunteers from the longitudinal, prospective, Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MRIs were analyzed for imaging markers of neurodegeneration: WMH and ventricular CSF (vCSF) volumes. The time before MCI, when the changes in WMH and vCSF burden accelerate, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow-up. Results During a follow-up duration of up to 19.6 years, 134 subjects converted to MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %vCSF volume increase occurred 3.7 years before the onset of MCI. Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) had both AD and significant ischemic cerebrovascular disease present. Conclusions Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathologic change that emerges early in the presymptomatic phase leading to MCI. Longitudinal changes in WMH may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease-modifying therapies prior to dementia onset.
Key findings
- Results During a follow-up duration of up to 19.6 years, 134 subjects converted to MCI.
- Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) had both AD and significant ischemic cerebrovascular disease present.
Why it matters
In 181 older adults who started out cognitively normal and had brain MRI every year for up to 19.6 years, the growth of white matter hyperintensities, which the study calls "a common indicator of cerebrovascular pathology," sped up on average about 10.6 years before mild cognitive impairment, while enlargement of the fluid-filled ventricles sped up only about 3.7 years before. Among 63 people who developed MCI and later had autopsy, only 28.5% had Alzheimer's alone and 24% had Alzheimer's plus significant vascular disease. This suggests blood-vessel-related brain changes start early and often occur alongside Alzheimer's, though it shows timing, not cause.
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Study details
- Study designlongitudinal study
- Participants134
- Effect size3.3%; 28.5%
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for 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 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 134 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 127 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.9 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 7.2× 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 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Jeffrey Alan Kaye: h-index 122 (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 22843262) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 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
Silbert, L. C., Dodge, H. H., Perkins, L. G., Sherbakov, L., Lahna, D., Erten-Lyons, D., et al. (2012). Trajectory of white matter hyperintensity burden preceding mild cognitive impairment. Neurology. https://doi.org/10.1212/wnl.0b013e3182661f2b
Vancouver
Silbert LC, Dodge HH, Perkins LG, Sherbakov L, Lahna D, Erten-Lyons D, et al. Trajectory of white matter hyperintensity burden preceding mild cognitive impairment. Neurology. 2012. doi:10.1212/wnl.0b013e3182661f2b. PMID: 22843262.
BibTeX
@article{silbert2012-22843262,
author = {Silbert, L. C. and Dodge, H. H. and Perkins, L. G. and Sherbakov, L. and Lahna, D. and Erten-Lyons, D. and Woltjer, R. and Shinto, L. and others},
title = {{Trajectory of white matter hyperintensity burden preceding mild cognitive impairment}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e3182661f2b},
pmid = {22843262},
url = {https://doi.org/10.1212/wnl.0b013e3182661f2b}
}
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