Non-REM Sleep Characteristics Predict Early Cognitive Impairment in an Aging Population

Abstract

Objective: Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults.Methods: This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night.Results: Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, P < 0.05), theta power (OR 0.018, P < 0.01), sigma power (OR 0.033, P < 0.05), and spindle maximal amplitude (OR 0.002, P < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment (P < 0.05).Conclusion: A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.

Modifiable Risk Factors for Alzheimer’s Disease

“…It is well established that in AD patients electroencephalograms are characteristic of increases in N1 and N2 NREM sleep and REM latency, and decreases in REM sleep, leading to an overall decrease in sleep duration (Loewenstein et al, 1982). Recent studies indicate that prolonged sleep duration could be indicative of at risk population (Westwood et al, 2017) and, in fact, NREM characteristics may provide evidence of an already deteriorated cognitive condition (Taillard et al, 2019). Due to the association between aging, cognition and sleep disorders, it has been proposed that sleep disturbances may lead to an increased risk for AD development (Roh et al, 2012).…”

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

“…Aβ decreases nonrapid eye movement sleep and increases wakefulness. Aβ upregulates the expression levels of tau, pTau, orexin A, and adenosine A1 receptor [260]. Orexin receptor antagonists (e.g., Suvorexant) have been proposed as potential candidates for the treatment of sleep disorders and BDs in AD [261].…”

Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies

“…In the present study, aged mice exhibit impairments in high frequency network oscillations, a shift into slow oscillation and deficit in connectivity at the OB circuit, which likely represent neurobiological bases underlying odor deficits olfactory memory deficits. The use of quantitative sleep EEG analysis has been established as a promising biomarker for aging people at risk of cognitive decline [112]. Olfactory decline with normal aging in humans appears to localize to the olfactory epithelium and higher cortical areas and therefore changes in EEG recordings predisposed the early onset of mild cognitive impairment.…”