Brain-based mechanisms of late-life depression: Implications for novel interventions

Late-life depression (LLD) is a particularly debilitating illness. Older adults suffering from depression commonly experience poor outcomes in response to antidepressant treatments, medical comorbidities, and declines in daily functioning. This review aims to further our understanding of the brain network dysfunctions underlying LLD that contribute to disrupted cognitive and affective processes and corresponding clinical manifestations. We provide an overview of a network model of LLD that integrates the salience network, the default mode network (DMN) and the executive control network (ECN). We discuss the brain-based structural and functional mechanisms of LLD with an emphasis on their link to clinical subtypes that often fail to respond to available treatments. Understanding the brain networks that underlie these disrupted processes can inform the development of targeted interventions for LLD. We propose behavioral, cognitive, or computational approaches to identifying novel, personalized interventions that may more effectively target the key cognitive and affective symptoms of LLD.