Journal Mobile Options
Table of Contents
Vol. 27, No. 4, 2009
Issue release date: April 2009
Cerebrovasc Dis 2009;27:384–391

Longitudinal Cognitive Decline in Subcortical Ischemic Vascular Disease – The LADIS Study

Jokinen H. · Kalska H. · Ylikoski R. · Madureira S. · Verdelho A. · van der Flier W.M. · Scheltens P. · Barkhof F. · Visser M.C. · Fazekas F. · Schmidt R. · O’Brien J. · Waldemar G. · Wallin A. · Chabriat H. · Pantoni L. · Inzitari D. · Erkinjuntti T.
aDepartment of Psychology and the bMemory Research Unit, Department of Neurology, University of Helsinki, Helsinki, Finland; cServiço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal; dDepartment of Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands; eDepartment of Neurology and MRI Institute, Medical University Graz, Graz, Austria; fInstitute for Ageing and Health, University of Newcastle, Newcastle-upon-Tyne, UK; gMemory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark; hInstitute of Clinical Neuroscience, Goteborg University, Gothenburg, Sweden; iDepartment of Neurology, Hôpital Lariboisière, Paris, France; jDepartment of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Erkinjuntti T: Vascular cognitive deterioration and stroke. Cerebrovasc Dis 2007;24(suppl 1):189–194.
  2. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW: Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm 2000;59(suppl):23–30.
  3. Chui H: Subcortical ischemic vascular dementia (SIVD). Neurol Clin 2007;25:717–740.
  4. Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC: Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426–436.
  5. Pohjasvaara T, Mäntylä R, Ylikoski R, Kaste M, Erkinjuntti T: Clinical features of MRI-defined subcortical vascular disease. Alzheimer Dis Assoc Disord 2003;17:236–242.
  6. Jokinen H, Kalska H, Ylikoski R, Madureira S, Verdelho A, Ferro JM, Gouw A, Scheltens P, Barkhof F, Visser MC, Fazekas F, Schmidt R, O’Brien J, Hennerici M, Baezner H, Waldemar G, Wallin A, Chabriat H, Pantoni L, Inzitari D, Erkinjuntti D: MRI-defined subcortical ischemic vascular disease: Baseline clinical and neuropsychological findings. The LADIS study. Cerebrovasc Dis 2009;27:336–344.
  7. Jokinen H, Kalska H, Mäntylä R, Pohjasvaara T, Ylikoski R, Hietanen M, Salonen O, Kaste M, Erkinjuntti T: Cognitive profile of subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2006;77:28–33.
  8. Pantoni L, Basile AM, Pracucci G, Asplund K, Bogousslavsky J, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, O’Brien J, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D: Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51–62.
  9. Inzitari D, Simoni M, Pracucci G, Poggesi A, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, Langhorne P, O’Brien J, Barkhof F, Visser MC, Wahlund LO, Waldemar G, Wallin A, Pantoni L: Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med 2007;167:81–88.
  10. Lawton MP, Brody EM: Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–186.
  11. APA: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), ed 4. Washington, American Psychiatric Association, 1994.
  12. Madureira S, Verdelho A, Ferro J, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O’Brien J, Pantoni L, Salvadori E, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D: Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data. Neuroepidemiology 2006;27:101–116.
  13. Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  14. Ferris SH: General measures of cognition. Int Psychogeriatr 2003;15(suppl 1):215–217.
  15. MacLeod CM: Half a century of research on the Stroop effect: an integrative review. Psychol Bull 1991;109:163–203.
  16. Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271–276.

    External Resources

  17. Van Straaten ECW, Fazekas F, Rostrup E, Scheltens P, Schmidt R, Pantoni L, Inzitari D, Waldemar G, Erkinjuntti T, Mäntylä R, Wahlund LO, Barkhof F: Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study. Stroke 2006;37:836–840.
  18. Prins ND, van Straaten EC, van Dijk EJ, Simoni M, van Schijndel RA, Vrooman HA, Koudstaal PJ, Scheltens P, Breteler MM, Barkhof F: Measuring progression of cerebral white matter lesions on MRI: visual rating and volumetrics. Neurology 2004;62:1533–1539.
  19. Scheltens P, Launer LJ, Barkhof F, Weinstein HC, van Gool WA: Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: interobserver reliability. J Neurol 1995;242:557–560.
  20. Wahlund LO, Almkvist O, Basun H, Julin P: MRI in successful aging, a 5-year follow-up study from the eighth to ninth decade of life. Magn Reson Imaging 1996;14:601–608.
  21. Schmidt R, Fazekas F, Kapeller P, Schmidt H, Hartung HP: MRI white matter hyperintensities: Three-year follow-up study of the Austrian Stroke Prevention Study. Neurology 1999;53:132–139.
  22. De Groot JC, de Leeuw FE, Oudkerk M, van Gijn J, Hofman A, Jolles J, Breteler MMB: Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol 2002;52:335–341.
  23. Longstreth WTJ, Arnold AM, Beauchamp NJJ, Manolio TA, Lefkowitz D, Jungreis C, Hirsch CH, O’Leary DH, Furberg CD: Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly. The Cardiovascular Health Study. Stroke 2005;36:56–61.
  24. Van der Flier WM, van der Vlies AE, Weverling-Rijnsburger AW, de Boer NL, Admiraal-Behloul F, Bollen EL, Westendorp RG, van Buchem MA, Middelkoop HA: MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic. Int J Geriatr Psychiatry 2005;20:1060–1066.
  25. Van den Heuvel DMJ, ten Dam VH, de Craen AJM, Admiraal-Behloul F, Olofsen H, Bollen ELEM, Jolles J, Murray HM, Blauw GJ, Westendorp RGJ, Buchem MA: Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population. J Neurol Neurosurg Psychiatry 2006;77:149–153.
  26. Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Jolles J, Koudstaal PJ, Hofman A, Breteler MMB: Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005;128:2034–2041.
  27. Garde E, Mortensen EL, Rostrup E, Paulson OB: Decline in intelligence is associated with progression in white matter hyperintensity volume. J Neurol Neurosurg Psychiatry 2005;76:1289–1291.
  28. Kramer JH, Mungas D, Reed BR, Wetzel ME, Burnett MM, Miller BL, Weiner MW, Chui HC: Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology 2007;21:412–418.
  29. Smith EE, Egorova S, Blacker D, Killiany RJ, Muzikansky A, Dickerson BC, Tanzi RE, Albert MS, Greenberg SM, Guttmann CR: Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol 2008;65:94–100.
  30. Van der Flier WM, van Straaten ECW, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P: Small vessel disease and general cognitive function in non-disabled elderly: the LADIS study. Stroke 2005;36:2116–2120.
  31. Carey CL, Kramer JH, Josephson SA, Mungas D, Reed BR, Schuff N, Weiner MW, Chui HC: Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly. Stroke 2008;39:397–402.
  32. Viswanathan A, Gschwendtner A, Guichard JP, Buffon F, Cumurciuc R, O’Sullivan M, Holtmannspötter M, Pachai C, Bousser MG, Dichgans M, Chabriat H: Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007;69:172–179.
  33. Gold G, Kovari E, Herrmann FR, Canuto A, Hof PR, Michel JP, Bouras C, Giannakopoulos P: Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia. Stroke 2005;36:1184–1188.
  34. Shim YS, Yang DW, Kim BS, Shon YM, Chung YA: Comparison of regional blood flow in two sets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT. J Neurol Sci 2006;250:85–91.
  35. Tekin S, Cummings JL: Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647–654.
  36. Tullberg M, Fletcher E, DeCarli C, Mungas D, Reed BR, Harvey DJ, Weiner MW, Chui HC, Jagust WJ: White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246–253.
  37. Brickman AM, Zimmerman ME, Paul RH, Grieve SM, Tate DF, Cohen RA, Williams LM, Clark CR, Gordon E: Regional white matter and neuropsychological functioning across the adult lifespan. Biol Psychiatry 2006;60:444–453.
  38. Lemay S, Bedard M-A, Routeau I, Tremblay PLG: Practice effect and test-retest reliability of attentional and executive tests in middle-aged to elderly subjects. Clin Neuropsychol 2004;18:284–302.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50