Psychological Medicine

Original Articles

Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study

A. Teodorczuka1 c1, M. J. Firbanka1, L. Pantonia2, A. Poggesia2, T. Erkinjunttia3, A. Wallina4, L.-O. Wahlunda5, P. Scheltensa6, G. Waldemara7, G. Schrottera8, J. M. Ferroa9, H. Chabriata10, H. Baznera11, M. Vissera6, D. Inzitaria2 and J. T. O'Briena1 on behalf of the LADIS Group

a1 Institute for Ageing and Health, Newcastle University, UK

a2 Department of Neurological and Psychiatric Sciences, University of Florence, Italy

a3 Memory Research Unit, Department of Neurology, University of Helsinki, Finland

a4 Institute of Clinical Neuroscience, Göteborg University, Sweden

a5 Karolinska University Hospital, Huddinge, Sweden

a6 Alzheimer Centre/Department of Neurology, VU University Hospital, Amsterdam, The Netherlands

a7 The Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark

a8 Department of Neurology, Medical University, Graz, Austria

a9 Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, Portugal

a10 Department of Neurology, Hopital Lariboisiere, Paris, France

a11 Department of Neurology, University of Heidelberg, Universitätsklinikum Mannheim, Germany


Background Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.

Method In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors.

Results Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08).

Conclusions Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

(Received January 09 2009)

(Revised May 15 2009)

(Accepted June 23 2009)

(Online publication August 12 2009)


c1 Address for correspondence: A. Teodorczuk, MRCPsych, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. (Email: