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Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study
van der Flier WM, van Straaten EC, Barkhof F, Ferro JM, Pantoni L, Basile AM, Inzitari D, Erkinjuntti T et al.. Journal of neurology, neurosurgery, and psychiatry, 2005-11-01
Topic: Brain proteins, microglia and lab models
Objective To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. Methods Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). Results The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p Conclusions These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.
Key findings
- Results The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)).
- Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05).
Why it matters
In 581 older people without disability, having either severe white matter hyperintensities or medial temporal lobe atrophy alone was not significantly linked to mild cognitive deficits, but having both together was linked to more than a fourfold increase. This is an observational study and does not test any treatment or prevention.
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Study details
- Participants639
- Effect sizeOR = 1.5; OR = 4.1
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | 3 / 4 | Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (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 | 2 / 4 | 639 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 124 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.4 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 4.0× 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 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Wiesje M. van der Flier: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Vrije Universiteit Amsterdam: institution h-index 1,014 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16227537) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Read the original
- DOI: 10.1136/jnnp.2005.064998
- PubMed: 16227537
- Original source →
- Free full text: Journal of Neurology Neurosurgery & Psychiatry →
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
van der Flier, W. M., van Straaten, E. C., Barkhof, F., Ferro, J. M., Pantoni, L., Basile, A. M., et al. (2005). Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp.2005.064998
Vancouver
van der Flier WM, van Straaten EC, Barkhof F, Ferro JM, Pantoni L, Basile AM, et al. Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. Journal of neurology, neurosurgery, and psychiatry. 2005. doi:10.1136/jnnp.2005.064998. PMID: 16227537.
BibTeX
@article{vanderflier2005-16227537,
author = {van der Flier, W. M. and van Straaten, E. C. and Barkhof, F. and Ferro, J. M. and Pantoni, L. and Basile, A. M. and Inzitari, D. and Erkinjuntti, T. and others},
title = {{Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2005},
doi = {10.1136/jnnp.2005.064998},
pmid = {16227537},
url = {https://doi.org/10.1136/jnnp.2005.064998}
}
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