Plasma Phosphorylated Tau and Neuropsychiatric Symptoms in Dementia with Lewy Bodies

Introduction: Neuropsychiatric symptoms (NPSs) are common in dementia with Lewy bodies (DLB) but their neurobiological mechanisms are poorly understood.

Methods: NPSs and cognition were assessed annually in participants (DLB n = 222; Alzheimer's disease [AD] n = 125) from the European DLB (E-DLB) Consortium, and plasma phosphorylated tau-181 (p-tau181) and p-tau231 concentrations were measured at baseline.

Results: Hallucinations, delusions, and depression were more common in DLB than in AD and, in a subgroup with longitudinal follow-up, persistent hallucinations and NPSs were associated with lower p-tau181 and p-tau231 in DLB. In adjusted linear mixed-effects models, hallucinations at baseline were associated with greater longitudinal cognitive impairment in DLB, with a significant interaction with p-tau231.

Discussion: Higher p-tau181 and p-tau231 levels were associated with a lower longitudinal risk of NPSs and hallucinations in early-stage DLB. However, the interaction between hallucinations and p-tau231 suggests that when AD co-pathology and hallucinations do co-exist in DLB that they may synergistically exacerbate cognitive decline.

Highlights: Neuropsychiatric symptoms (NPSs) were more common in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD). Lower plasma phosphorylated tau-231 (p-tau231) and p-tau181 levels were associated with persistent hallucinations in DLB. Lower plasma p-tau231 and p-tau181 levels were associated with an increased risk of persistent NPSs in early DLB. Hallucinations at baseline were associated with greater cognitive dysfunction in DLB, and there was an interaction with p-tau231.