Associations of informant-based sleep reports with Alzheimer’s disease pathologies

Abstract

Purpose: Recent studies have found associations of increased brain amyloid beta (Aβ) accumulation and several abnormal sleep-wake patterns, including shorter latency and increased fragmentation in preclinical Alzheimer’s disease (AD). There is little known about the relationship between sleep and tau. The objective of this study was to understand the associations of both tau and Aβ with early signs of sleep and night-time behavior changes in clinically normal elderly adults. Specifically, we have addressed the question of how informant-based subjective sleep reports are linked to regional [18F]flortaucipir and [18F] florbetapir uptake. Methods: Imaging and behavioral data from 35 subjects were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The Neuropsychiatric Inventory Sleep (NPI-sleep) Questionnaire was used to assess the sleep and night-time behavior changes. Regional tau-positron emission tomography (PET) (entorhinal, brainstem) and Aβ-PET (posterior cingulate, precuneus, medial orbitofrontal) uptake values were calculated. A series of linear regression analyses were used to determine the combination of sleep symptoms that built the best models to predict each pathology. Results: Informant-based reports of abnormal night-time behavior (NPI questions k3, k5, and k8) were significantly associated with increased entorhinal tau and Aβ (all regions) accumulation. Interestingly, informant-based reports of sleep deficiencies without abnormal nigh-time activity (NPI questions k1, k2, and k6) were negatively associated with entorhinal tau burden. Conclusion: Detection of abnormal night-time behaviors (wandering, pacing, other inappropriate activities) by family members indicates early signs of both AD pathologies and may encourage the affected individuals to seek help by health care providers for detailed cognitive/neurobehavioral assessments.