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  2. Changes in white...
  3. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort
Research

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2477 (Published 06 July 2009) Cite this as: BMJ 2009;339:b2477
  1. Domenico Inzitari, full professor of neurology and chairman of the department1,
  2. Giovanni Pracucci, neurologist1,
  3. Anna Poggesi, neurologist PhD student1,
  4. Giovanna Carlucci, assistant professor in neurology1,
  5. Frederik Barkhof, full professor of neuroradiology2,
  6. Hugues Chabriat, professor of neurology3,
  7. Timo Erkinjuntti, full professor of neurology4,
  8. Franz Fazekas, full professor of neurology5,
  9. José M Ferro, chairman professor of neurology6,
  10. Michael Hennerici, full professor of neurology and chairman of the department7,
  11. Peter Langhorne, full professor of geriatric medicine8,
  12. John O’Brien, professor of old age psychiatry9,
  13. Philip Scheltens, full professor of neurology2,
  14. Marieke C Visser, assistant professor of neurology2,
  15. Lars-Olof Wahlund, professor of geriatric medicine10,
  16. Gunhild Waldemar, full professor of neurology11,
  17. Anders Wallin, full professor of neuropsychiatry12,
  18. Leonardo Pantoni, consultant neurologist1
  19. on behalf of the LADIS Study Group
  1. 1Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy
  2. 2Department of Radiology and Neurology, VU Medical Centre, Amsterdam, Netherlands
  3. 3Department of Neurology, Hopital Lariboisiere, Paris, France
  4. 4Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland
  5. 5Department of Neurology and MRI Institute, Medical University Graz, Austria
  6. 6Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria Lisboa, Portugal
  7. 7Department of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany
  8. 8Academic Department for Geriatric Medicine, Glasgow Royal Infirmary, Glasgow
  9. 9Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne
  10. 10Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Huddinge, Sweden
  11. 11Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
  12. 12Institute of Clinical Neuroscience, Gothenburg University, Gothenburg, Sweden
  1. Correspondence to: D Inzitari inzitari{at}neuro.unifi.it
  • Accepted 13 February 2009

Abstract

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes.

Design Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints.

Setting 11 European centres.

Participants 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy.

Main outcome measure Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke.

Results Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect.

Conclusion The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.

Footnotes

  • We thank Patrizia Trallori for secretarial assistance throughout the LADIS study.

  • Participating centres and personnel

  • Timo Erkinjuntti, Tarja Pohjasvaara, Pia Pihanen, Raija Ylikoski, Hanna Jokinen, Meija-Marjut Somerkoski, Riitta Mäntylä, Oili Salonen (Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland); Franz Fazekas, Reinhold Schmidt, Stefan Ropele, Brigitte Rous, Katja Petrovic, Ulrike Garmehi, Alexandra Seewann (Department of Neurology and Department of Radiology, Division of Neuroradiology, Medical University Graz, Graz, Austria); José M Ferro, Ana Verdelho, Sofia Madureira, Carla Moleiro (Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal); Philip Scheltens, van Straaten, Frederik Barkhof, Alida Gouw, Wiesje van der Flier (Department of Radiology and Neurology, VU Medical Centre, Amsterdam, Netherlands); Anders Wallin, Michael Jonsson, Karin Lind, Arto Nordlund, Sindre Rolstad, Ingela Isblad (Institute of Clinical Neuroscience, Goteborg University, Gothenburg, Sweden); Lars-Olof Wahlund, Milita Crisby, Anna Pettersson, Kaarina Amberla (Karolinska Institutet, Department of Neurbiology, Care Sciences and Society; Karolinska University Hospital Huddinge, Sweden); Hugues Chabriat, Karen Hernandez, Annie Kurtz, Dominique Hervé, Sarah Benisty, Jean Pierre Guichard (Department of Neurology, Hopital Lariboisiere, Paris, France); Michael Hennerici, Christian Blahak, Hansjorg Baezner, Martin Wiarda, Susanne Seip (Department of Neurology, University of Heidelberg, Klinikum Mannheim, Germany); Gunhild Waldemar, Egill Rostrup, Charlotte Ryberg, Tim Dyrby, Olaf B Paulson, Ellen Garde (Memory Disorders Research Group, Department of Neurology, Rigshospitalet, and the Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Copenhagen University Hospitals, Denmark); John O’Brien, Sanjeet Pakrasi, Mani Krishnan, Andrew Teodorczuk, Michael Firbank, Philip English, Thais Minett (Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne).

  • The coordinating centre is at Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy): Domenico Inzitari (study Coordinator); Luciano Bartolini, Anna Maria Basile, Eliana Magnani, Monica Martini, Mario Mascalchi, Marco Moretti, Leonardo Pantoni, Anna Poggesi, Giovanni Pracucci, Emilia Salvadori, Michela Simoni. The LADIS Steering Committee comprises Domenico Inzitari, (study coordinator), Timo Erkinjuntti, Philip Scheltens, Marieke Visser, Kjell Asplund (up to 2005), and Peter Langhorne (from 2005).

  • Contributors: DI was study coordinator and substantially contributed to the study concept, design, analysis, and interpretation of data, and writing of the paper. GP was study data manager and contributed to the analysis and interpretation of data, and writing of the paper. AP contributed to the analysis and interpretation of data, study performance, and writing of the paper. GC contributed to the study design, study performance, and writing of the paper. FB contributed to the study design, study performance, magnetic resonance imaging analysis, and writing of the paper. HC, TE, FF, JMF, MH, PL, and MCV contributed to the writing of the paper and the monitoring of the study. JO’B contributed to the study concept and design, study performance, and writing of the paper. PS contributed to the study design, study performance, and writing of the paper. L-OW, GW, AW, and LP. LP was the deputy study coordinator, and DI is guarantor.

  • Funding and sponsor: The LADIS study is supported by the European Union within the Vth European Framework Program “Quality of life and management of living resources” (1998-2002), contract No QLRT-2000-00446 as a concerted action. The sponsor had no role in the study design, collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

  • Competing interests: None declared.

  • Ethical approval: The study protocol was approved by each centre’s ethics committee.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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