Depression and mood dysregulation are among the most prevalent and clinically consequential neuropsychiatric symptoms (NCD-NPS) across the spectrum of neurocognitive disorders (NCD). These symptoms impair quality of life, increase carer burden, and are associated with accelerated functional and cognitive decline. At the same time, major depressive disorder across the lifespan represents a potentially modifiable risk factor for later-life dementia, while late-onset depressive symptoms may signal prodromal neurodegeneration. This dual role positions depression at a critical intersection between symptom management and dementia prevention. This International Psychogeriatric Association (IPA) white paper was developed through expert consensus meetings held in Buenos Aires (2024) and Kanazawa (2025) to identify key knowledge gaps and define global priorities in nomenclature, biomarkers, treatment, and prevention. Current diagnostic frameworks inadequately capture dementia-specific depressive phenotypes and the marked heterogeneity of depression in NCD, including variation by disease stage, dementia subtype, symptom profile, apathy overlap, sleep and circadian disruption, exposomic risk, caregiver context, and treatment response. Although advances in neuroimaging, inflammatory markers, molecular biomarkers, digital phenotyping, and life-course risk assessment offer promise, none are yet validated for routine diagnostic stratification or treatment selection. Pharmacologic therapies demonstrate modest and inconsistent efficacy, and no agent is specifically approved for depression comorbid with dementia. Psychosocial, behavioral, caregiver-inclusive, sleep-focused, and multimodal interventions remain essential but require greater scalability and integration into care systems. The IPA Depression Workgroup proposes a next-decade roadmap emphasizing NCD-specific diagnostic criteria, biomarker-informed and exposome-aware subtyping, development of targeted and scalable interventions, routine attention to sleep health and caregiver context, and integration of depression prevention into brain health and NCD care frameworks to advance precision psychiatry and dementia risk reduction.
