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

J Clin Psychiatry 2010;71(10):1379-1385
10.4088/JCP.09m05349gry

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 (Archana.Singh-Manoux@inserm.fr).