We investigated changes in neuropsychiatric symptoms (NPS) severity using the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and survival between neuropathologically defined cohorts of Alzheimer's Disease dementia (ADD), dementia with Lewy bodies (DLB), ADD with Lewy body pathology not meeting neuropathological criteria for DLB (AD-LB), and controls.

NPS are frequent in ADD but a higher NPS burden is associated with DLB. Both AD-LB and DLB cases have faster cognitive decline compared to ADD but less is known about NPS evolution in these pathological groups.

Cases from the AZSAND with a final neuropathologic diagnosis of DLB (±AD co-pathology; n=65), AD-LB (n=89), ADD (without LB) (n=140), and controls (n=82) were included. Total NPI-Q within 2.5 years of death and at enrollment were calculated for all groups. ANCOVA (adjusting for age, sex, baseline MMSE and cognitive symptom duration) with pairwise comparisons, Kaplan-Meier curves and log-rank test were used to compare groups.

Mean time between first and last NPI-Q assessments were different between controls and DLB (p=0.03). NPI-Q scores at enrollment were highest in AD-LB (7.33 ± 4.85), and different (p<0.001) from DLB (5.10 ± 3.37), ADD (4.54 ± 3.63), and controls (1.78 ± 1.70). At final evaluation, NPI-Q scores were significantly higher in DLB (10.04 ± 6.28), AD-LB (8.0 ± 4.68), and ADD (7.61 ± 5.05) when compared to controls (2.78 ± 3.97) (all p<0.001).  DLB and ADD demonstrated significant increases in NPI-Q severity during follow up (p­<0.001). ADD had longer median survival time (5.8 years) compared to AD-LB (4.0 years) and DLB (3.9 years, p=0.004). Subjects with NPS had a shorter median survival time (3.4 years) compared to subjects without NPS (6.5 years; p=0.002).

AD-LB pathology correlated with higher NPI-Q scores earlier in the disease course. Expression of DLB clinical features leads to faster progression, reduced survival and more severe NPS prior to death.