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Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia
van Straaten EC, Harvey D, Scheltens P, Barkhof F, Petersen RC, Thal LJ, Jack CR, DeCarli C et al.. Journal of neurology, 2008-09-25
Topic: Brain proteins, microglia and lab models
Background White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear. Methods Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression. Results 55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value Conclusion PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.
Key findings
- Results 55 of the 152 (36.2 %) aMCI subjects progressed to AD.
- Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value Conclusion PVH are associated with an increased risk of progression from aMCI to AD.
- This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.
Why it matters
In 152 people with amnestic mild cognitive impairment from a three-year donepezil/vitamin E trial, 55 (36.2%) progressed to Alzheimer's disease. Of the white matter regions scored on their entry MRI, only periventricular hyperintensities were linked to a higher risk of progression (hazard ratio 1.59, 95% CI 1.24–2.05), after adjusting for age, education and treatment arm. The authors suggest this vascular-type damage contributes to Alzheimer's onset independently of Alzheimer pathology, but this is an association in a trial subset, not proof of cause.
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Study details
- Effect sizeHR = 1.59
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design and sample size because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology) |
| Journal's citation record | 2 / 4 | Journal of Neurology: journal h-index 208 (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 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 110 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.5 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 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 | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18825439) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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Read the original
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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
van Straaten, E. C., Harvey, D., Scheltens, P., Barkhof, F., Petersen, R. C., Thal, L. J., et al. (2008). Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia. Journal of neurology. https://doi.org/10.1007/s00415-008-0874-y
Vancouver
van Straaten EC, Harvey D, Scheltens P, Barkhof F, Petersen RC, Thal LJ, et al. Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia. Journal of neurology. 2008. doi:10.1007/s00415-008-0874-y. PMID: 18825439.
BibTeX
@article{vanstraaten2008-18825439,
author = {van Straaten, E. C. and Harvey, D. and Scheltens, P. and Barkhof, F. and Petersen, R. C. and Thal, L. J. and Jack, C. R. and DeCarli, C. and others},
title = {{Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia}},
journal = {Journal of neurology},
year = {2008},
doi = {10.1007/s00415-008-0874-y},
pmid = {18825439},
url = {https://doi.org/10.1007/s00415-008-0874-y}
}
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