Advancing therapeutic approaches for agitation: a neurorelational perspective

Agitation is a common, distressing and difficult-to-treat symptom in dementia, linked to emotional dysregulation and interpersonal stress. Degenerative and compensatory changes in the locus coeruleus-noradrenergic (LC-NA) system have been implicated in agitation in Alzheimer’s disease. However, neuropathology alone does not fully explain why some individuals are more prone to agitation than others. We explore how premorbid mentalizing capacity (the ability to understand one’s own and others’ mental states) in both care recipients and caregivers may influence agitation propensity. Mentalizing, rooted in early attachment experiences, supports emotion regulation but may be compromised under stress in the context of neurodegeneration and neuropsychiatric symptoms, and this could increase the likelihood of escalation of care. We propose a neurorelational framework for understanding and addressing agitation, integrating neurobiological and socio-emotional perspectives. Targeting both care recipients’ LC-NA system and caregivers’ mentalizing capacity may represent a personalized intervention strategy to mitigate effects of neurodegeneration on ‘neuropsychiatric reserve’.