Toward Precision Neuropsychiatry of Dementia: Neuropsychiatric Symptoms as Multidimensional Clinical Phenotypes
TL;DR
A precision neuropsychiatry framework that conceptualises NPS—including apathy, agitation, psychosis, depression, and sleep disturbances—as multidimensional clinical phenotypes is introduced that stratifies NPS based on disease background, clinical stage, neural networks, biological aging, physical vulnerability, and psychosocial context to optimise differential diagnosis, prognostic prediction, and targeted interventions.
Abstract
Neuropsychiatric symptoms (NPS) are the most clinically consequential manifestations of dementia, yet they are frequently underestimated as secondary behavioural complications. This review introduces a precision neuropsychiatry framework that conceptualises NPS—including apathy, agitation, psychosis, depression, and sleep disturbances—as multidimensional clinical phenotypes. These phenotypes bridge neurodegeneration, biological aging, brain network disruption, psychosocial context, functional decline, and caregiver burden. We trace the conceptual evolution from dementia to neurocognitive disorders, and from behavioural and psychological symptoms of dementia (BPSD) to NPS and mild behavioural impairment (MBI). Precision neuropsychiatry stratifies NPS based on disease background, clinical stage, neural networks, biological aging, physical vulnerability, and psychosocial context to optimise differential diagnosis, prognostic prediction, and targeted interventions. Although conventional symptom‐based classification remains practically useful, it must be complemented by biological, functional, and contextual stratification; identical symptom labels often arise from distinct mechanisms and express differently based on personality, life history, environmental mismatch, and available resources. Emerging evidence from MBI, neuroimaging, brain‐age paradigms, frailty, neuroinflammation, Alzheimer's disease (AD) biomarkers, and international consensus criteria supports this multidimensional shift. Future research should advance from cross‐sectional symptom descriptions toward longitudinal, mechanism‐informed, and context‐sensitive models to translate these findings into real‐world psychogeriatric care.