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Persistent Depressive Symptoms and Cognitive Function in Late Midlife: The Whitehall II Study

Archana Singh-Manoux, PhD; Tasnime N. Akbaraly, PhD; Michael Marmot, MD, PhD; Maria Melchior, ScD; Joël Ankri, MD, PhD; Séverine Sabia, PhD; and Jane E. Ferrie, PhD

Published: June 1, 2010

Article Abstract

Objective: Depression has been widely linked to poor cognition and dementia in the elderly. However, comorbidity at older ages does not allow an assessment of the role of mental health as a risk factor for cognitive outcomes. We examined the association between depressive symptoms, measured 6 times over an 18-year period, and cognitive deficits in late midlife.

Method: Of the 10,308 participants in the Whitehall II study, 4,271 men and women (aged 35-55 years at baseline) were followed up for 18 years, during which depressive symptoms were assessed 6 times using the General Health Questionnaire depression subscale. The follow-up was from 1985-1988 to 2002-2004. Cognition was assessed at the most recent wave (2002-2004, mean age 61 years, range 50-74 years) using 6 tests: memory, reasoning, vocabulary, 2 tests of verbal fluency, and the MMSE (Mini Mental State Examination). Cognitive deficit was defined as MMSE score < 28 and performance in the worst sex-specific quintile for the other tests.

Results: History of depressive symptoms, once or more in the 6 times assessed, had a weak association with some of the cognitive tests. However, in analysis adjusted for sociodemographic variables, diabetes, coronary heart disease, hypertension, stroke, and antidepressant use, persistent depressive symptoms (4-6 times) were associated with cognitive deficits on all tests: memory (OR = 1.91; 95% CI, 1.36-2.67), reasoning (OR = 1.60; 95% CI, 1.15-2.20), vocabulary (OR = 1.75; 95% CI, 1.27-2.41), phonemic fluency (OR = 1.40; 95% CI, 1.00-1.94), semantic fluency (OR = 1.68; 95% CI, 1.20-2.35), and the MMSE (OR = 1.76; 95% CI, 1.25-2.50).

Conclusions: Our data show that depressive episodes tend to persist in some individuals, and these individuals are at a greater risk of cognitive deficits in late midlife.

J Clin Psychiatry

Submitted: May 13, 2009; accepted November 10, 2009.

Online ahead of print: June 1, 2010 (doi:10.4088/JCP.09m05349gry).

Corresponding author: Archana Singh-Manoux, PhD, National Institute for Health & Medical Research; INSERM, U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Bât 15/16, 16 Ave Paul Vaillant Couturier, 94807 Villejuif Cedex, France (

Volume: 71

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