Late-Onset Depression in an Aging World: A Multidimensional Perspective on Risks, Mechanisms, and Treatment

Background: Late-onset depression (LOD) represents a distinct clinical and biological phenotype emerging in the context of global population ageing. This study aims to synthesize current evidence on the epidemiology, risk factors, mechanistic pathways, and therapeutic approaches of LOD, integrating biological, psychological, and social dimensions. Methods: This narrative review synthesizes recent evidence across epidemiology, clinical symptomatology, neurobiology, and treatment. Where conceptually appropriate or empirically overlapping, we incorporate findings from the broader late-life depression (LLD) literature. Results: LOD emerges (as a distinct clinical and biological entity in later life) as a clinically and biologically meaningful presentation of depression in later life, representing a minority of depressive cases. It is defined by prominent apathy, psychomotor slowing, and cognitive impairment, and is closely linked to frailty, medical comorbidity, and heightened dementia risk. Pathophysiological mechanisms converge on vascular, inflammatory, oxidative, and neuroplasticity pathways, while psychosocial adversity further shapes onset and course. Treatment prioritizes efficacy and tolerability amid multiple morbidity; SSRIs and SNRIs are first-line, with pro-dopaminergic or dual-action agents addressing anhedonia and apathy, and neuromodulation or augmentation strategies reserved for resistance. Integrative approaches combining pharmacotherapy, psychotherapy, and lifestyle interventions are essential to optimize outcomes in aging populations. Conclusions: Late-onset depression (is a distinct, biologically and psychosocially driven disorder) represents a biologically and psychosocially enriched subtype in its own within the spectrum of late-life depression, requiring integrated, personalized care. Addressing neurovascular mechanisms, psychosocial adversity, and prevention through coordinated geriatric and psychiatric strategies may improve outcomes in aging populations.