Sleep dysregulation, memory impairment, and CSF biomarkers during different levels of neurocognitive functioning in Alzheimer's disease course

Background: Alzheimer's disease (AD) is frequently accompanied by sleep impairment, which can induce AD-related neurodegeneration. We herein investigated the sleep architecture, cognition, and cerebrospinal fluid (CSF) biomarkers (tau proteins and β-amyloid₄₂) during AD progression from subjective cognitive impairment (SCI) to mild cognitive impairment (MCI) and eventually to AD dementia, and compared the results with cognitively normal (CN) subjects. Methods: We included patients affected by SCI, MCI, mild AD, and moderate-to-severe AD in our study along with CN subjects as controls. All the subjects underwent nocturnal polysomnography to investigate sleep, neuropsychological testing to evaluate cognition, and lumbar puncture for CSF AD biomarkers assessment. Results: Sleep (both rapid eye movement (REM) and non-REM sleep) and memory function are both progressively impaired during the course of AD from SCI to mild and subsequently to moderate AD. Further, sleep dysregulation appears earlier than cognitive deterioration, with a reduction of CSF β-amyloid₄₂ level. Conclusion: Sleep, memory, and CSF AD biomarkers are closely interrelated in AD progression from the earliest asymptomatic and preclinical stages of the disease related in AD since the earliest and preclinical stages of the disease.