Skip to main content Accessibility help
×
Home

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

  • A. Teodorczuk (a1), M. J. Firbank (a1), L. Pantoni (a2), A. Poggesi (a2), T. Erkinjuntti (a3), A. Wallin (a4), L.-O. Wahlund (a5), P. Scheltens (a6), G. Waldemar (a7), G. Schrotter (a8), J. M. Ferro (a9), H. Chabriat (a10), H. Bazner (a11), M. Visser (a6), D. Inzitari (a2) and J. T. O'Brien (a1)...

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.

Copyright

Corresponding author

*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: Andrew.Teodorczuk@ncl.ac.uk)

References

Hide All
Alexopoulos, GS (2006). The vascular depression hypothesis: 10 years later. Biological Psychiatry 60, 13041305.
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, 125136.
Blazer, DG 2nd, Hybels, CF (2005). Origins of depression in later life. Psychological Medicine 35, 12411252.
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, 10091060.
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, 10711076.
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, 351356.
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, 606612.
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, 674679.
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, 189198.
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, 471481.
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, 663669.
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, 11891196.
Hatano, S (1976). Experience from a multicentre stroke register: a preliminary report. Bulletin of the World Health Organization 54, 541553.
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, 8188.
Krishnan, KR, Hays, JC, Blazer, DG (1997). MRI-defined vascular depression. American Journal of Psychiatry 154, 497501.
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, 166168.
Lawton, MP, Brody, EM (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9, 179186.
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, 678682.
MacFall, JR, Payne, ME, Provenzale, JE, Krishnan, KR (2001). Medial orbital frontal lesions in late-onset depression. Biological Psychiatry 49, 803806.
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, 982984.
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, 834841.
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, P338P347.
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, 5162.
Scheltens, P, Barkhof, F, Fazekas, F (2003). White-matter changes on MRI as surrogate marker. International Psychogeriatrics 15 (Suppl. 1), 261265.
Steffens, DC, Krishnan, KR, Crump, C, Burke, GL (2002). Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. Stroke 33, 16361644.
Steffens, DC, Potter, GG (2008). Geriatric depression and cognitive impairment. Psychological Medicine 38, 163175.
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, 212217.
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, 836840.
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, 375381.
Yesavage, JA (1988). Geriatric Depression Scale. Psychopharmacological Bulletin 24, 709711.

Keywords

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

  • A. Teodorczuk (a1), M. J. Firbank (a1), L. Pantoni (a2), A. Poggesi (a2), T. Erkinjuntti (a3), A. Wallin (a4), L.-O. Wahlund (a5), P. Scheltens (a6), G. Waldemar (a7), G. Schrotter (a8), J. M. Ferro (a9), H. Chabriat (a10), H. Bazner (a11), M. Visser (a6), D. Inzitari (a2) and J. T. O'Brien (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed