A transdiagnostic review of neuroimaging studies of apathy and disinhibition in dementia

Apathy and disinhibition are common and highly distressing neuropsychiatric symptoms associated with negative outcomes in persons with dementia. This paper is a critical review of functional and structural neuroimaging studies of these symptoms transdiagnostically in dementia of the Alzheimer type, which is characterized by prominent amnesia early in the disease course, and behavioural variant frontotemporal dementia, characterized by early social-comportmental deficits. We describe the prevalence and clinical correlates of these symptoms and describe methodological issues, including difficulties with symptom definition and different measurement instruments. We highlight the heterogeneity of findings, noting however, a striking similarity of the set of brain regions implicated across clinical diagnoses and symptoms. These regions involve several key nodes of the salience network, and we describe the functions and anatomical connectivity of these brain areas, as well as present a new theoretical account of disinhibition in dementia. Future avenues for research are discussed, including the importance of transdiagnostic studies, measuring subdomains of apathy and disinhibition, and examining different units of analysis for deepening our understanding of the networks and mechanisms underlying these extremely distressing symptoms.