Associations between neuropsychiatric symptoms and pathology in clinicopathologically defined Alzheimer's disease, Alzheimer's disease with Lewy bodies, and dementia with Lewy bodies

BackgroundNeuropsychiatric symptoms (NPS) are frequent in Alzheimer's disease (AD) dementia, but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co-occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). NPS trajectories over disease course in these subgroups is not well understood.ObjectiveWe investigated changes in NPS severity over time, at two time points, comparing clinicopathologically defined cohorts of AD (without LB), ADLB, DLB, and controls.MethodsCases with two available Neuropsychiatric Inventory-Questionnaire (NPIQ), at the time of enrollment and within 2.5 years of death, were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Differences and rate of change in NPIQ scores were compared between AD (n = 75), ADLB (n = 48) DLB (n = 65), and controls (n = 32) with covariates for age, sex, and cognition.ResultsFirst NPIQ scores were highest in ADLB when compared to AD (p = 0.04) and controls (p = 0.01) but not different from DLB. A significant increase in NPS severity was observed in DLB and AD (p < 0.001) over a mean follow up time of 4.9 ± 3.0 years, and the rate of change was significantly greater in DLB when compared to other groups. Final NPIQ scores were highest in DLB when compared to AD (p = 0.03) but not ADLB, and in DLB, ADLB, and AD than controls (<i>all</i> p < 0.001).ConclusionsEarly NPS burden as well as NPS severity progression rate, independently of cognitive status, might be useful clinical metrics and may help predict underlying pathological diagnoses.