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Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community
Brickman AM, Provenzano FA, Muraskin J, Manly JJ, Blum S, Apa Z, Stern Y, Brown TR et al.. Archives of neurology, 2012-12-01
Topic: Amyloid, tau and blood-test diagnosis
BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.
Key findings
- RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03).
- It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions.
Why it matters
In this community study, greater white matter hyperintensity volume in the parietal lobe predicted who went on to develop Alzheimer's disease, while hippocampal volume did not. This suggests that small vessel cerebrovascular disease may play a role in the development of Alzheimer's disease, though it is not clear whether parietal white matter hyperintensities are just a marker of cerebrovascular burden or reflect a distinct type of injury.
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Study details
- Study designlongitudinal study
- Participants717
- Effect sizeHR = 0.419; HR = 0.302; HR = 1.197
- Evidence strengthModerate
How this study scored 65/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 717 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 257 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 10.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 2 / 4 | Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Richard P Mayeux: h-index 158 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22945686) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 100 | — |
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Read the original
- DOI: 10.1001/archneurol.2012.1527
- PubMed: 22945686
- 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'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
Brickman, A. M., Provenzano, F. A., Muraskin, J., Manly, J. J., Blum, S., Apa, Z., et al. (2012). Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community. Archives of neurology. https://doi.org/10.1001/archneurol.2012.1527
Vancouver
Brickman AM, Provenzano FA, Muraskin J, Manly JJ, Blum S, Apa Z, et al. Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community. Archives of neurology. 2012. doi:10.1001/archneurol.2012.1527. PMID: 22945686.
BibTeX
@article{brickman2012-22945686,
author = {Brickman, A. M. and Provenzano, F. A. and Muraskin, J. and Manly, J. J. and Blum, S. and Apa, Z. and Stern, Y. and Brown, T. R. and others},
title = {{Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community}},
journal = {Archives of neurology},
year = {2012},
doi = {10.1001/archneurol.2012.1527},
pmid = {22945686},
url = {https://doi.org/10.1001/archneurol.2012.1527}
}
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