The neurobiology of depression in later-life: Clinical, neuropsychological, neuroimaging and pathophysiological features

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.