Abstract

Abstract Objective Neuropsychiatric symptoms (NPS) are common in neurodegenerative disease, but longitudinal studies using large autopsy-confirmed samples are lacking. Our primary aim was to investigate progression of NPS over time in autopsy-confirmed Alzheimer’s disease (ad), Lewy body disease (LBD), and mixed (ad+LBD) cohorts. Methods Data on individuals (age > =50) with autopsy-confirmed ad (N = 1568), ad+LBD (N = 349), and LBD (N = 142) was obtained from the National Alzheimer’s Coordinating Center (Mean visits = 2.61). Neuropsychiatric Inventory Questionnaire (NPI-Q) and 15-item Geriatric Depression Scale (GDS) scores were used to measure NPS. Multilevel zero-inflated binomial regression models were used to assess if NPI-Q and GDS scores differed among ad, ad+LBD, and LBD groups over time. Covariates included: years from baseline to final visit, cognitive status at baseline (i.e., normal, MCI, or dementia), demographic characteristics, MMSE, Functional Activities Questionnaire, and psychotropic treatment of psychiatric conditions. Results Higher NPI-Q and GDS scores were observed at baseline in the LBD group compared to ad (p’s < 0.001). NPI-Q scores increased over time in the LBD group compared to ad+LBD and ad groups (90% CI). GDS scores differed among all groups at baseline (95% CI), with more rapid increase in the LBD group vs. ad and ad+LBD groups. Conclusions Overall, the course of NPS differs among disease pathologies. Those with pure LBD appear to have more severe NPS over time compared to those with ad and ad+LBD. Depressive symptoms increased more in LBD and ad+LBD compared to ad over time. Future research examining clinical outcomes related to NPS burden (care needs, caregiver burden, and life expectancy) is needed.

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