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Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study
  1. Hanna Jokinen1,2,
  2. Charlotte Ryberg4,
  3. Hely Kalska1,
  4. Raija Ylikoski2,
  5. Egill Rostrup3,
  6. Mikkel B Stegmann5,
  7. Gunhild Waldemar4,
  8. Sofia Madureira6,
  9. José M Ferro6,
  10. Elizabeth C W van Straaten7,
  11. Philip Scheltens7,
  12. Frederik Barkhof7,
  13. Franz Fazekas8,
  14. Reinhold Schmidt8,
  15. Giovanna Carlucci9,
  16. Leonardo Pantoni9,
  17. Domenico Inzitari9,
  18. Timo Erkinjuntti2,
  19. on behalf of the LADIS group*
  1. 1Department of Psychology, University of Helsinki, Helsinki, Finland
  2. 2Memory Research Unit, Department of Neurology, University of Helsinki, Helsinki, Finland
  3. 3Danish Research Center for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark
  4. 4Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
  5. 5Informatics and Mathematical Modelling, Technical University of Denmark, Copenhagen, Denmark
  6. 6Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal
  7. 7Department of Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
  8. 8Department of Neurology and MRI Institute, Medical University Graz, Graz, Austria
  9. 9Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
  1. Correspondence to:
 MsH Jokinen
 Department of Neurology, Helsinki University Central Hospital, PO Box 302, FIN-00029 HUS, Helsinki, Finland; hanna.jokinen{at}


Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions.

Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH).

Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors.

Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion.

Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

  • CC1, rostrum and genu
  • CC2, rostral body
  • CC3, midbody
  • CC4, isthmus
  • CC5, splenium
  • LADIS, Leukoaraiosis and Disability
  • MMSE, Mini-Mental State Examination
  • MRI, magnetic resonance imaging
  • VADAS-cog, Vascular Dementia Assessment Scale—Cognitive
  • WMH, white matter hyperintensities

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  • Published Online First 6 October 2006

  • * A list of collaborators of the LADIS Study is presented in the appendix.

  • Funding: The Leukoaraiosis and Disability Study was supported by the European Union (grant QLRT-2000-00446). The work of HJ was supported by the Finnish Graduate School of Psychology, the Emil Aaltonen Foundation and the Biomedicum Helsinki Foundation. Funding was also provided by the Danish Velux Foundation and the Danish Alzheimer Research Foundation.

  • Competing interests: PS is an associate editor for the Journal of Neurology, Neurosurgery and Psychiatry but was not involved in the article’s reviewing process.