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

Published online by Cambridge University Press:  12 August 2009

A. Teodorczuk ,
M. J. Firbank ,
L. Pantoni ,
A. Poggesi ,
T. Erkinjuntti ,
A. Wallin ,
L.-O. Wahlund ,
P. Scheltens ,
G. Waldemar  and
G. Schrotter
...Show all authors
A. Teodorczuk*
Affiliation:
Institute for Ageing and Health, Newcastle University, UK
M. J. Firbank
Affiliation:
Institute for Ageing and Health, Newcastle University, UK
L. Pantoni
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Florence, Italy
A. Poggesi
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Florence, Italy
T. Erkinjuntti
Affiliation:
Memory Research Unit, Department of Neurology, University of Helsinki, Finland
A. Wallin
Affiliation:
Institute of Clinical Neuroscience, Göteborg University, Sweden
L.-O. Wahlund
Affiliation:
Karolinska University Hospital, Huddinge, Sweden
P. Scheltens
Affiliation:
Alzheimer Centre/Department of Neurology, VU University Hospital, Amsterdam, The Netherlands
G. Waldemar
Affiliation:
The Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark
G. Schrotter
Affiliation:
Department of Neurology, Medical University, Graz, Austria
J. M. Ferro
Affiliation:
Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, Portugal
H. Chabriat
Affiliation:
Department of Neurology, Hopital Lariboisiere, Paris, France
H. Bazner
Affiliation:
Department of Neurology, University of Heidelberg, Universitätsklinikum Mannheim, Germany
M. Visser
Affiliation:
Alzheimer Centre/Department of Neurology, VU University Hospital, Amsterdam, The Netherlands
D. Inzitari
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Florence, Italy
J. T. O'Brien
Affiliation:
Institute for Ageing and Health, Newcastle University, UK
*
*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: [email protected])
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Abstract

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.

Keywords

Disabilitylate-life depressionlongitudinal studyMRIwhite-matter lesions
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 4 , April 2010 , pp. 603 - 610
Copyright
Copyright © Cambridge University Press 2009

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