Vascular and metabolic risk factors of late-life depression

Late-life depression (LLD) is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, cognitive decline, and increased mortality. The mechanisms underlying LLD are incompletely understood. The heterogeneity of depression complicates research into the underlying mechanisms, and factors involved in LLD may differ from those involved in early-life depression. This narrative review provides an overview of (micro-)vascular and metabolic factors involved in the development of LLD. Evidence suggests that cerebral small vessel disease, generalized microvascular dysfunction, and metabolic risk factors, including diabetes and inflammation, may contribute to the development of LLD, while the role of neurodegeneration needs further indepth investigation. Accordingly, vascular and metabolic factors may provide promising targets for the prevention and improvement of treatment of LLD. Guidelines to screen for LLD in cardiovascular care need further implementation, as do integrated care approaches that treat LLD and diabetes jointly. However, intervention studies are needed to assess which interventions are appropriate and most effective in clinical practice.