White matter lesions: Spatial heterogeneity, links to risk factors, cognition, genetics, and atrophy
Habes M, Sotiras A, Erus G, Toledo JB, Janowitz D, Wolk DA, Shou H, Bryan NR et al.. Neurology, 2018-08-03
Topic: Brain proteins, microglia and lab models
Objectives To investigate spatial heterogeneity of white matter lesions or hyperintensities (WMH). Methods MRI scans of 1,836 participants (median age 52.2 ± 13.16 years) encompassing a wide age range (22-84 years) from the cross-sectional Study of Health in Pomerania (Germany) were included as discovery set identifying spatially distinct components of WMH using a structural covariance approach. Scans of 307 participants (median age 73.8 ± 10.2 years, with 747 observations) from the Baltimore Longitudinal Study of Aging (United States) were included to examine differences in longitudinal progression of these components. The associations of these components with vascular risk factors, cortical atrophy, Alzheimer disease (AD) genetics, and cognition were then investigated using linear regression. Results WMH were found to occur nonuniformly, with higher frequency within spatially heterogeneous patterns encoded by 4 components, which were consistent with common categorizations of deep and periventricular WMH, while further dividing the latter into posterior, frontal, and dorsal components. Temporal trends of the components differed both cross-sectionally and longitudinally. Frontal periventricular WMH were most distinctive as they appeared in the fifth decade of life, whereas the other components appeared later in life during the sixth decade. Furthermore, frontal WMH were associated with systolic blood pressure and with pronounced atrophy including AD-related regions. AD polygenic risk score was associated with the dorsal periventricular component in the elderly. Cognitive decline was associated with the dorsal component. Conclusions These results support the hypothesis that the appearance of WMH follows age and disease-dependent regional distribution patterns, potentially influenced by differential underlying pathophysiologic mechanisms, and possibly with a differential link to vascular and neurodegenerative changes.
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APA 7th
Habes, M., Sotiras, A., Erus, G., Toledo, J. B., Janowitz, D., Wolk, D. A., et al. (2018). White matter lesions: Spatial heterogeneity, links to risk factors, cognition, genetics, and atrophy. Neurology. https://doi.org/10.1212/wnl.0000000000006116
Vancouver
Habes M, Sotiras A, Erus G, Toledo JB, Janowitz D, Wolk DA, et al. White matter lesions: Spatial heterogeneity, links to risk factors, cognition, genetics, and atrophy. Neurology. 2018. doi:10.1212/wnl.0000000000006116. PMID: 30076276.
BibTeX
@article{habes2018-30076276,
author = {Habes, M. and Sotiras, A. and Erus, G. and Toledo, J. B. and Janowitz, D. and Wolk, D. A. and Shou, H. and Bryan, N. R. and others},
title = {{White matter lesions: Spatial heterogeneity, links to risk factors, cognition, genetics, and atrophy}},
journal = {Neurology},
year = {2018},
doi = {10.1212/wnl.0000000000006116},
pmid = {30076276},
url = {https://doi.org/10.1212/wnl.0000000000006116}
}
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Key findings
- Results WMH were found to occur nonuniformly, with higher frequency within spatially heterogeneous patterns encoded by 4 components, which were consistent with common categorizations of deep and periventricular WMH, while further dividing the latter into posterior, frontal, and dorsal components.
- Furthermore, frontal WMH were associated with systolic blood pressure and with pronounced atrophy including AD-related regions.
- AD polygenic risk score was associated with the dorsal periventricular component in the elderly.
- Cognitive decline was associated with the dorsal component.
- Conclusions These results support the hypothesis that the appearance of WMH follows age and disease-dependent regional distribution patterns, potentially influenced by differential underlying pathophysiologic mechanisms, and possibly with a differential link to vascular and neurodegenerative changes.
Why it matters
In MRI scans of 1,836 German adults, with follow-up scans of 307 older US adults, white matter lesions clustered in four distinct regions. Lesions near the front of the brain's fluid spaces appeared earliest, in the fifth decade of life, and were associated with higher systolic blood pressure and with shrinkage in Alzheimer's-related areas. A different, "dorsal" pattern was associated with an Alzheimer's polygenic risk score in older people and with cognitive decline. These are associations, not proof of cause, but they suggest different lesion locations may reflect different vascular and neurodegenerative processes.
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Study details
- Study designcross-sectional
- Participants1,836
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for 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 | 4 / 12 | A snapshot of people at one point in 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 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,836 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 142 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.2 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.8× 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 | 3 / 4 | Cited 52 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Christos A. Davatzikos: h-index 124 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30076276) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000006116
- PubMed: 30076276
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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