Depression, frailty, and all-cause mortality: a cohort study of men older than 75 years

Depression is associated with increased mortality, but it is unclear if this relationship is truly causal.

To determine the relative mortality associated with past and current depression, taking into account the effect of frailty.

Prospective longitudinal cohort study of 2565 men aged 75 years or over living in metropolitan Perth, Western Australia, who completed the third wave of assessments of the Health In Men Study throughout 2008.

All-cause mortality data were derived from Australian death records up to June 17, 2013. History of past depression and age of onset of symptoms were obtained from direct questioning and from electronic health record linkage. Diagnosis of current major depressive symptoms followed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision guidelines. We considered that participants were frail if they showed evidence of impairment in 3 or more of the 5 domains on the fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale. Other measured factors included age, education, living arrangements, smoking and alcohol history, and physical activity.

558 participants died during mean period of follow-up of 4.2 ± 1.1 years. The annual death rate per thousand was 50 for men without depression, 52 for men with past depression, and 201 for men with major depressive symptoms at baseline. The crude mortality hazard was 4.26 (95% confidence interval = 2.98, 6.09) for men with depression at baseline compared with never depressed men, and 1.79 (95% confidence interval = 1.21, 2.62) after adjustment for frailty. Further decline in mortality hazard was observed after adjustment for other measured factors.

Current, but not past, depression is associated with increased mortality, and this excess mortality is strongly associated with frailty. Interventions designed to decrease depression-related mortality in later life may need to focus on ameliorating frailty in addition to treating depression.