Neuropsychiatric symptom-role reorganization in amyloid PET-positive Alzheimer's disease: An expanded-cohort analysis

BackgroundNeuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) often occur in clusters, and their clinical meaning may depend on the symptoms with which they co-occur. Whether a previously identified NPS cluster pattern remains transportable after expansion of an amyloid PET-positive cohort is uncertain.ObjectiveTo assess the transportability of a previously published NPS cluster model and to characterize symptom-role reorganization after cohort expansion.MethodsWe analyzed 301 consecutive drug-naive patients with probable AD and positive ¹⁸F-FC119S amyloid PET. The cohort comprised the previously published 143-patient reference cohort and 158 newly enrolled, non-overlapping patients who constituted the extension cohort. Twelve Korean Neuropsychiatric Inventory domains were coded as present or absent. Hierarchical clustering was repeated in the extension cohort and in the full cohort, and changes in individual symptom relationships were examined.ResultsThe original four-cluster solution was only partly reproduced. Aggression, disinhibition, and aberrant motor behavior remained closely grouped, while anxiety and irritability also remained linked and were joined by euphoria. Hallucination shifted into the behavioral-dyscontrol cluster, whereas depression, apathy, nighttime behavior, and eating abnormality formed a vegetative-apathy cluster. Delusion formed a single-domain cluster and, together with aggression, aberrant motor behavior, and disinhibition, showed the largest stage-associated prevalence differences between Clinical Dementia Rating (CDR) 0.5 and CDR 1.0-2.0.ConclusionsNPS clusters in amyloid PET-positive AD may not represent fixed syndromes. A symptom-role framework that distinguishes preserved relationships, reorganized symptoms, and independent stage-linked symptoms may provide a more clinically informative understanding of NPS in AD.