Neuropsychiatric Inventory -Assessed Nighttime Behavior Accompanies, but Does Not Precede, Progressive Cognitive Decline Independent of Alzheimer's Disease Histopathology

Background: The relationship between sleep, neuropathology, and clinical manifestations of Alzheimer's disease (AD) remains controversial. Objective: To determine whether nighttime behaviors (NTB) are associated with the development of AD histopathology or cognitive decline. Methods: We compared NTB prevalence in subjects with or without AD lesions, and with or without progressive cognitive decline. Subjects with either absent or severe plaques and tangles were identified from the National Alzheimer's Disease Coordinating Center data sets and classified as cognitively declining if the standard deviation from their individual mean Mini-Mental Status Examination score was =2, and stable if <2 regardless of their initial score. NTB was assessed using the Neuropsychiatric Inventory Questionnaire Quick Version (NPI-Q). Results: NTBwas significantly greater in decliners than stable subjects in the group with severe histopathology as determined by frequent plaques (p = 0.003) or high Braak stage (p = 0.002). A similar significant trend was observed in subjects with absent plaques (p = 0.019) or tangles (p = 0.006). The prevalence of NTB was comparable between stable AD and non-AD subjects. NTB severity scores showed a similar pattern. Conclusion: The development of NTB as assessed by NPI-Q in subjects with or without AD lesions occurred concurrently with cognitive decline. Among cognitively stable subjects, the presence of AD histopathology did not alter NTB prevalence. Thus, NTB disruptions at the gross granularity level assessed by NPI-Q were much more closely related to cognitive decline than the formation of pathological lesions. Factors other than AD histopathology may mediate the association between NTB and cognitive decline.