Neuropsychiatric Inventory-Questionnaire Assessed Nighttime Behaviors in Cognitively Asymptomatic Patients with Pathologically Confirmed Alzheimer's Disease Predict More Rapid Cognitive Deterioration

Background: The temporal relationship between sleep, Alzheimer's disease (AD), and cognitive impairment remains to be further elucidated. Objective: First, we aim to determine whether the Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed nighttime behaviors prior to cognitive decline influence the rate of cognitive deterioration in pathologically confirmed AD, and second, to assess the possible interactions with APOE allele and cerebral amyloid angiopathy (CAA). Methods: The rate of cognitive decline between cognitively asymptomatic participants from the National Alzheimer Coordinating Center who eventually received a neuropathologic diagnosis of AD with (+NTB) or without (-NTB) nighttime behaviors were compared using independent samples t-test. Participants were stratified by APOE carrier and CAA status. Demographic and patient characteristics were assessed using descriptive statistics, and the independent samples t-test was used for continuous variables and chi-square test for categorical variables. The significance level was set at p <= 0.05. Results: The rate of cognitive decline was greater in +NTB (n = 74; 3.30 points/year) than -NTB (n = 330; 2.45 points/year) (p = 0.016), even if there was no difference in cognitive status at onset. This difference was restricted to APOE epsilon 4 carriers (p = 0.049) and positive CAA participants (p = 0.020). Significance was not reached in non-carriers (p = 0.186) and negative CAA (p = 0.364). APOE and CAA were not differentially distributed between the NTB groups. Conclusion: NPI-Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly deteriorating cognition in patients with AD neuropathology who are also carriers of APOE epsilon 4 or show CAA.