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White matter hyperintensities and imaging patterns of brain ageing in the general population
Habes M, Erus G, Toledo JB, Zhang T, Bryan N, Launer LJ, Rosseel Y, Janowitz D et al.. Brain : a journal of neurology, 2016-02-24
Topic: Risk, prevention and care in population studies
White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P = 0.001), diabetes mellitus (P = 0.023), smoking (P = 0.002) and education level (P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population.
Key findings
- White matter hyperintensities are associated with increased risk of dementia and cognitive decline.
- The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania.
- Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia.
- To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them.
- Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively.
Why it matters
In a large population-based sample, people with high white matter hyperintensity burden showed more brain atrophy patterns typical of aging and Alzheimer's disease, and white matter hyperintensities significantly mediated the age effect on the Alzheimer's-like pattern. The study reports associations and a possible causal role for cardiovascular risk and white matter hyperintensities, but it tests no treatment, cure or prevention.
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Study details
- Participants2,367
- Effect size10.4%; 21.6%; 70.2%
- Evidence strengthLow
How this study scored 64/100
Published in a leading specialty journal. Scored zero for study design 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,367 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 | 6 / 7 | Cited 428 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 35.7 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 27.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 3 / 4 | Cited 118 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 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26912649) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 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
Habes, M., Erus, G., Toledo, J. B., Zhang, T., Bryan, N., Launer, L. J., et al. (2016). White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain : a journal of neurology. https://doi.org/10.1093/brain/aww008
Vancouver
Habes M, Erus G, Toledo JB, Zhang T, Bryan N, Launer LJ, et al. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain : a journal of neurology. 2016. doi:10.1093/brain/aww008. PMID: 26912649.
BibTeX
@article{habes2016-26912649,
author = {Habes, M. and Erus, G. and Toledo, J. B. and Zhang, T. and Bryan, N. and Launer, L. J. and Rosseel, Y. and Janowitz, D. and others},
title = {{White matter hyperintensities and imaging patterns of brain ageing in the general population}},
journal = {Brain : a journal of neurology},
year = {2016},
doi = {10.1093/brain/aww008},
pmid = {26912649},
url = {https://doi.org/10.1093/brain/aww008}
}
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