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Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study
van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T et al.. Stroke, 2005-09-01
Topic: Risk, prevention and care in population studies
Background and purpose On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. Methods Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). Results In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. Conclusions We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.
Key findings
- Results In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS.
- When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score.
- Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent.
- Conclusions We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly.
- These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.
Why it matters
In 633 independently living elderly people, greater severity of white matter hyperintensities and lacunes on MRI was associated with worse scores on general cognitive tests. This is an observational study and does not show that treating small vessel disease prevents or cures Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stroke) |
| Journal's citation record | 3 / 4 | Stroke: journal h-index 455 (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 | 2005 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 323 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.0 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 11.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Philip Scheltens: h-index 181 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Helsinki: institution h-index 1,201 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16141425) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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APA 7th
van der Flier, W. M., van Straaten, E. C., Barkhof, F., Verdelho, A., Madureira, S., Pantoni, L., et al. (2005). Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke. https://doi.org/10.1161/01.str.0000179092.59909.42
Vancouver
van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, et al. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke. 2005. doi:10.1161/01.str.0000179092.59909.42. PMID: 16141425.
BibTeX
@article{vanderflier2005-16141425,
author = {van der Flier, W. M. and van Straaten, E. C. and Barkhof, F. and Verdelho, A. and Madureira, S. and Pantoni, L. and Inzitari, D. and Erkinjuntti, T. and others},
title = {{Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study}},
journal = {Stroke},
year = {2005},
doi = {10.1161/01.str.0000179092.59909.42},
pmid = {16141425},
url = {https://doi.org/10.1161/01.str.0000179092.59909.42}
}
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