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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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References

Alexopoulos, GS (2006). The vascular depression hypothesis: 10 years later. Biological Psychiatry 60, 1304–1305.CrossRefGoogle ScholarPubMed
Baldwin, R, Jeffries, S, Jackson, A, Sutcliffe, C, Thacker, N, Scott, M, Burns, A (2004). Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors. Psychological Medicine 34, 125–136.CrossRefGoogle ScholarPubMed
Blazer, DG 2nd, Hybels, CF (2005). Origins of depression in later life. Psychological Medicine 35, 1241–1252.CrossRefGoogle ScholarPubMed
Chalmers, J, MacMahon, S, Mancia, G, Whitworth, J, Beilin, L, Hansson, L, Neal, B, Rodgers, A, Ni Mhurchu, C, Clark, T (1999). 1999 World Health Organization – International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clinical and Experimental Hypertension 21, 1009–1060.Google ScholarPubMed
de Groot, JC, de Leeuw, FE, Oudkerk, M, Hofman, A, Jolles, J, Breteler, MM (2000). Cerebral white matter lesions and depressive symptoms in elderly adults. Archives of General Psychiatry 57, 1071–1076.CrossRefGoogle ScholarPubMed
Fazekas, F, Chawluk, JB, Alavi, A, Hurtig, HI, Zimmerman, RA (1987). MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Roentgenology 149, 351–356.CrossRefGoogle ScholarPubMed
Firbank, MJ, Lloyd, AJ, Ferrier, N, O'Brien, JT (2004). A volumetric study of MRI signal hyperintensities in late-life depression. American Journal of Geriatric Psychiatry 12, 606–612.CrossRefGoogle ScholarPubMed
Firbank, MJ, O'Brien, JT, Pakrasi, S, Pantoni, L, Simoni, M, Erkinjuntti, T, Wallin, A, Wahlund, L-O, van Straaten, I, Inzitari, D (2005). White matter hyperintensities and depression – preliminary results from the LADIS study. International Journal of Geriatric Psychiatry 20, 674–679.CrossRefGoogle ScholarPubMed
Folstein, MF, Folstein, SE, McHugh, PR (1975). ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189–198.CrossRefGoogle Scholar
Gelinas, I, Gauthier, L, McIntyre, M, Gauthier, S (1999). Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. American Journal of Occupational Therapy 53, 471–481.CrossRefGoogle ScholarPubMed
Godin, O, Dufouil, C, Maillard, P, Delcroix, N, Mazoyer, B, Crivello, F, Alperovitch, A, Tzourio, C (2008). White matter lesions as a predictor of depression in the elderly: the 3C-Dijon study. Biological Psychiatry 63, 663–669.CrossRefGoogle ScholarPubMed
Gouw, AA, Van der Flier, WM, van Straaten, EC, Barkhof, F, Ferro, JM, Baezner, H, Pantoni, L, Inzitari, D, Erkinjuntti, T, Wahlund, LO, Waldemar, G, Schmidt, R, Fazekas, F, Scheltens, P (2006). Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study. Journal of Neurology 253, 1189–1196.CrossRefGoogle ScholarPubMed
Hatano, S (1976). Experience from a multicentre stroke register: a preliminary report. Bulletin of the World Health Organization 54, 541–553.Google Scholar
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, L-O, Waldemar, G, Wallin, A, Pantoni, L; LADIS Study Group (2007). Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Archives of Internal Medicine 167, 81–88.CrossRefGoogle ScholarPubMed
Krishnan, KR, Hays, JC, Blazer, DG (1997). MRI-defined vascular depression. American Journal of Psychiatry 154, 497–501.Google ScholarPubMed
Kumar, A, Ajilore, O (2008). Magnetic resonance imaging and late-life depression: potential biomarkers in the era of personalized medicine. American Journal of Psychiatry 165, 166–168.CrossRefGoogle ScholarPubMed
Lawton, MP, Brody, EM (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9, 179–186.CrossRefGoogle ScholarPubMed
Levy, RM, Steffens, DC, McQuoid, DR, Provenzale, JM, MacFall, JR, Krishnan, KRR (2003). MRI lesion severity and mortality in geriatric depression. American Journal of Geriatric Psychiatry 11, 678–682.CrossRefGoogle ScholarPubMed
MacFall, JR, Payne, ME, Provenzale, JE, Krishnan, KR (2001). Medial orbital frontal lesions in late-onset depression. Biological Psychiatry 49, 803–806.CrossRefGoogle ScholarPubMed
O'Brien, J, Ames, D, Chiu, E, Schweitzer, I, Desmond, P, Tress, B (1998). Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study. British Medical Journal 317, 982–984.CrossRefGoogle ScholarPubMed
O'Brien, JT, Firbank, MJ, Krishnan, MS, van Straaten, ECW, van der Flier, WM, Petrovic, K, Pantoni, L, Simoni, M, Erkinjuntti, T, Wallin, A, Wahlund, L-O, Inzitari, D; LADIS Study Group (2006). White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study. American Journal of Geriatric Psychiatry 14, 834–841.CrossRefGoogle ScholarPubMed
Ormel, J, Rijsdijk, FV, Sullivan, M, van Sonderen, E, Kempen, GI (2002). Temporal and reciprocal relationship between IADL/ADL disability and depressive symptoms in late life. Journals of Gerontology. Series B, Psychological Sciences and Social Sciences 57, P338–P347.CrossRefGoogle Scholar
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, L-O, Waldemar, G, Wallin, A, Inzitari, D (2005). Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 24, 51–62.CrossRefGoogle ScholarPubMed
Scheltens, P, Barkhof, F, Fazekas, F (2003). White-matter changes on MRI as surrogate marker. International Psychogeriatrics 15 (Suppl. 1), 261–265.CrossRefGoogle ScholarPubMed
Steffens, DC, Krishnan, KR, Crump, C, Burke, GL (2002). Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. Stroke 33, 1636–1644.CrossRefGoogle ScholarPubMed
Steffens, DC, Potter, GG (2008). Geriatric depression and cognitive impairment. Psychological Medicine 38, 163–175.CrossRefGoogle ScholarPubMed
Teodorczuk, A, O'Brien, JT, Firbank, MJ, Pantoni, L, Poggesi, A, Erkinjuntti, T, Wallin, A, Wahlund, LO, Gouw, A, Waldemar, G, Schmidt, R, Ferro, JM, Chabriat, H, Bazner, H, Inzitari, D (2007). White matter changes and late-life depressive symptoms: longitudinal study. British Journal of Psychiatry 191, 212–217.CrossRefGoogle ScholarPubMed
van Straaten, EC, Fazekas, F, Rostrup, E, Scheltens, P, Schmidt, R, Pantoni, L, Inzitari, D, Waldemar, G, Erkinjuntti, T, Mantyla, R, Wahlund, LO, Barkhof, F (2006). Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study. Stroke 37, 836–840.CrossRefGoogle ScholarPubMed
Versluis, CE, van der Mast, RC, van Buchem, MA, Bollen, ELEM, Blauw, GJ, Eekhof, JAH, van der Wee, NJA, de Craen, AJM (2006). Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease: the PROSPER study. International Journal of Geriatric Psychiatry 21, 375–381.CrossRefGoogle Scholar
Yesavage, JA (1988). Geriatric Depression Scale. Psychopharmacological Bulletin 24, 709–711.Google ScholarPubMed