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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
  1. W M van der Flier1,
  2. E C W van Straaten1,
  3. F Barkhof2,
  4. J M Ferro3,
  5. L Pantoni4,
  6. A M Basile4,
  7. D Inzitari4,
  8. T Erkinjuntti5,
  9. L O Wahlund6,
  10. E Rostrup7,
  11. R Schmidt8,
  12. F Fazekas8,
  13. P Scheltens1,
  14. on behalf of the LADIS study group
  1. 1Department of Neurology and Alzheimer Centre, Vrije Universiteit Medical Centre, Amsterdam, Netherlands
  2. 2Department of Radiology and Image Analysis Centre (IAC), Vrije Universiteit Medical Centre
  3. 3Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal
  4. 4Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
  5. 5Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland
  6. 6Neurotec department, Section of Clinical Geriatrics, Karolinska Universitetssjukhuset, Huddinge University Hospital, Huddinge, Sweden
  7. 7Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
  8. 8Department of Neurology and MRI Institute, Medical University, Graz, Austria
  1. Correspondence to:
 Dr Wiesje M van der Flier
 Department of Neurology and Alzheimer Centre, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, Netherlands;


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<0.05).

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.

  • IADL, instrumental activities of daily living
  • LADIS, leukoaraiosis and disability project
  • MMSE, mini-mental state examination
  • MTA, medial temporal lobe atrophy
  • WMH, white matter hyperintensities
  • MRI
  • elderly people
  • cognition

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  • Competing interests: Philip Scheltens is an associate editor of JNNP but had no role in reviewing or accepting this paper.