Mapping Sleep’s Oscillatory Events as a Biomarker of Alzheimer’s Disease

Abstract

Objective: Memory-associated neural circuits produce oscillatory events within single-channel sleep electroencephalography (EEG), including theta bursts (TBs), sleep spindles (SPs) and multiple subtypes of slow waves (SWs). Changes in the temporal "coupling" of these events are proposed to serve as a biomarker for early stages of Alzheimer's disease (AD) pathogenesis. Methods: We analyzed data from 205 aging adults, including single-channel sleep EEG, cerebrospinal fluid (CSF) AD-associated biomarkers, and Clinical Dementia Rating® (CDR®) scale. Individual SW events were sorted into high and low transition frequencies (TF) subtypes. We utilized time-frequency spectrogram locations within sleep EEG to "map" the precision of SW-TB and SW-SP neural circuit coupling in relation to amyloid positivity (by CSF Aβ42/Aβ40 threshold), cognitive impairment (by CDR), and CSF levels of AD-associated biomarkers. Results: Cognitive impairment was associated with lower TB spectral power in both high and low TF SW-TB coupling (p<0.001, p=0.001). Cognitively unimpaired, amyloid positive aging adults demonstrated lower precision of the neural circuits propagating high TF SW-TB (p<0.05) and low TF SW-SP (p<0.005) event coupling, compared to cognitively unimpaired amyloid negative individuals. Biomarker correlations were significant for high TF SW-TB coupling with CSF Aβ42/Aβ40 (p=0.005), phosphorylated-tau181 (p<0.005), and total-tau (p<0.05). Low TF SW-SP coupling was also correlated with CSF Aβ42/Aβ40 (p<0.01). Interpretation: Loss of integrity in neural circuits underlying sleep-dependent memory processing can be measured for both SW-TB and SW-SP coupling in spectral time-frequency space. Breakdown of sleep's memory circuit integrity is associated with amyloid positivity, higher levels of AD-associated pathology, and cognitive impairment.

Sleep Deprivation, Sleep Disorders, and Chronic Disease

“…Sleep is far from a passive state; it is a vital process for brain restoration and regulation. Inadequate sleep disrupts critical neural processes and impairs cognitive functioning (14,15). Altering these processes provides a mechanistic link through which insufficient sleep contributes to the onset or worsening of mental health, brain disorders, and chronic diseases.…”

The potential and prospects of sleep biomarkers in early Alzheimer's disease diagnosis

“…An analysis of data from 205 elderly adults, including sleep EEG, Alzheimer's disease-related biomarkers in cerebrospinal fluid, and clinical dementia assessment scales, revealed that cognitive impairment was related to reduced spectral power in TBs. Individuals with normal cognition but positive for amyloid-β showed lower accuracy in the coupling of certain neural circuits, and the coupling of some neural circuits was correlated with biomarkers in cerebrospinal fluid, such as Aβ42/Aβ40, phosphorylated tau181, and total tau [13].…”