[Late-life depression and frailty-Epidemiological, clinical and neurobiological associations]

Depression is the most common mental disorder in older adults and is influenced by age-related processes. Frailty is a well-established clinical expression of ageing that implies a state of increased vulnerability to stressor events as well as increased risks of disability, hospitalization and death. Neurobiological findings will disentangle the comorbidity of frailty and depression and may inform future management of depression in old age.

This narrative review provides an overview of the comorbidity of late-life depression and frailty, with a focus on neuroscientific findings that are organized within the research domain criteria (RDoC) framework.

More than one third of old people with depression are affected by frailty, which results in more chronic depression and in poorer efficacy and tolerability of antidepressant medication. Depression and frailty share motivational and psychomotor characteristics, particularly apathy, decreased physical activity and fatigue. In patients with frailty, altered activity of the supplementary motor cortex is associated with motor performance deficits. Patients with late-life depression and apathy are characterized by abnormal structure and altered functional connectivity of the reward network and the salience network, along with altered functional connectivity of these networks with premotor brain areas.

Identifying frailty in older adults with depression is relevant for prognostic assessment and treatment. A better understanding of the neuronal mechanisms of comorbidity will provide potential targets for future personalized therapeutic interventions.