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Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD
Yoshita M, Fletcher E, Harvey D, Ortega M, Martinez O, Mungas DM, Reed BR, DeCarli CS.. Neurology, 2006-12-01
Topic: Risk, prevention and care in population studies
Objective To analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons. Results Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk. Conclusions Differences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.
Key findings
- Results Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis.
- After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk.
- Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis.
- In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC.
- Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk.
Why it matters
Total white matter hyperintensity volumes were associated with age, vascular risk factors, and diagnosis, with significant differences between cognitively normal and Alzheimer disease subjects in posterior periventricular regions and the splenium of the corpus callosum. MCI subjects had intermediate values at all regions.
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Study details
- Study designpost-hoc analysis
- Participants26
- Evidence strengthLow
How this study scored 56/100
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 (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “post-hoc analysis”, which our rubric does not rank (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 | 1 / 5 | 2006 — older than 20 years, still counted |
| Sample size | 1 / 4 | 26 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 | 6 / 7 | Cited 436 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.8 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 4 / 6 | Cited 10.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 27 other studies in this library |
| Still being cited | 3 / 4 | Cited 64 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Charles S DeCarli: h-index 150 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Davis: institution h-index 1,257 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17190943) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
- DOI: 10.1212/01.wnl.0000249119.95747.1f
- PubMed: 17190943
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Yoshita, M., Fletcher, E., Harvey, D., Ortega, M., Martinez, O., Mungas, D. M., et al. (2006). Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology. https://doi.org/10.1212/01.wnl.0000249119.95747.1f
Vancouver
Yoshita M, Fletcher E, Harvey D, Ortega M, Martinez O, Mungas DM, et al. Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology. 2006. doi:10.1212/01.wnl.0000249119.95747.1f. PMID: 17190943.
BibTeX
@article{yoshita2006-17190943,
author = {Yoshita, M. and Fletcher, E. and Harvey, D. and Ortega, M. and Martinez, O. and Mungas, D. M. and Reed, B. R. and DeCarli, C. S.},
title = {{Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD}},
journal = {Neurology},
year = {2006},
doi = {10.1212/01.wnl.0000249119.95747.1f},
pmid = {17190943},
url = {https://doi.org/10.1212/01.wnl.0000249119.95747.1f}
}
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