Insights from human sleep research on neural mechanisms of Alzheimer’s disease

The current research in the field of sleep and AD is increasing in importance, denoting a possible innovative future in terms of non-invasive and early interventions and prevention strategies. The above-mentioned results on sleep electroencephalogram in relation with AD have to be considered as preliminary reports, because other confirmations are needed. Future researches should propose complex and integrated experimental protocols, in order to provide concurrent electrophysiological, behavioral, anatomical and neuropsychological data. At this purpose, longitudinal studies that follow the entire course of the pathology, since the preclinical stage of the disease are needed. Further investigations on the role of specific NREM sleep components are also required, with the aim of confirming the original and promising existing evidence

Sleep and β-Amyloid deposition in alzheimer disease: insights on mechanisms and possible innovative treatments

The preclinical stage of AD is characterized by β-amyloid (Aβ) aggregation into amyloid plaques and tau phosphorylation and aggregation into neurofibrillary tangles. There is a consensus on the importance of sleep within this context: the bidirectional relationship between sleep and AD pathology is supported by growing evidence that proved that the occurrence of sleep changes starting from the preclinical stage of AD, many years before the onset of cognitive decline. Hence, we review the most recent studies on sleep disturbances related to Aβ and the effects of sleep deprivation on Aβ accumulation in animal and human models. We also discuss evidence on the role of sleep in clearing the brain of toxic metabolic by-products, with original findings of the clearance activity of the glymphatic system stimulated by sleep. Furthermore, starting from new recent advances about the relationship between slow-wave sleep (SWS) and Aβ burden, we review the results of recent electroencephalographic (EEG) studies in order to clarify the possible role of SWS component disruption as a novel mechanistic pathway through which Aβ pathology may contribute to cognitive decline and, conversely, the eventual useful role of SWS in facilitating Aβ clearance. Finally, we discuss some promising innovative, effective, low-risk, non-invasive interventions, although empirical evidence on the efficacy of sleep interventions in improving the course of AD is at the very beginning

Sleep-based interventions in Alzheimer’s disease: promising approaches from prevention to treatment along the disease trajectory

The multifactorial nature of Alzheimer’s disease (AD) has led scientific researchers to focus on the modifiable and treatable risk factors of AD. Sleep fits into this context, given the bidirectional relationship with AD confirmed by several studies over the last years. Sleep disorders appear at an early stage of AD and continue throughout the entire course of the pathology. Specifically, sleep abnormalities, such as more fragmented sleep, increase in time of awakenings, worsening of sleep quality and primary sleep disorders raise with the severity and progression of AD. Intervening on sleep, therefore, means acting both with prevention strategies in the pre-clinical phase and with treatments during the course of the disease. This review explores sleep disturbances in the different stages of AD, starting from the pre-clinical stage. Particular attention is given to the empirical evidence investigating obstructive sleep apnea (OSA) disorder and the mechanisms overlapping and sharing with AD. Next, we discuss sleep-based intervention strategies in the healthy elderly population, mild cognitive impairment (MCI), and AD patients. We mention interventions related to behavioral strategies, combination therapies, and bright light therapy, leaving extensive space for new and raising evidence on continuous positive air pressure (CPAP) treatment effectiveness. Finally, we clarify the role of NREM sleep across the AD trajectory and consider the most recent studies based on the promising results of NREM sleep enhancement, which use innovative experimental designs and techniques

EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease

Patients with Alzheimer’s disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eyemovement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer’s disease progression

In search of sleep biomarkers of Alzheimer's disease: K-Complexes do not discriminate between patients with mild cognitive impairment and healthy controls

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer's disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/ MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioratio

Pandemic dreams: quantitative and qualitative features of the oneiric activity during the lockdown due to COVID-19 in Italy

Objective: The lockdown due to COVID-19 pandemic had a strong impact on daily habits, emotional experience, mental health and sleep. A large body of evidence suggests that dreams are affected by both waking experiences and sleep pattern. In this view, the lockdown should have induced intense modifications in dreaming activity. The aim of the study was to assess dream features during the lockdown in Italy. Methods: We used an online survey to collect self-reported demographic, clinical, sleep and dream data. Our sample included 1091 participants. Results: Results point to an increased dream frequency, emotional load, vividness, bizarreness and length during the lockdown, compared to a pre-lockdown period. Higher dream frequency and specific qualitative features were found in females and subjects with poor sleep quality, nocturnal disruptive behaviours and depressive symptoms. Most of the dream features assessed during the lockdown were predicted by age, gender, depressive symptoms, presence/absence of other people at home, and territorial area. A specific focus on sleep features revealed that sleep duration and several sleep quality indexes were the best predictors of dream variables. During the lockdown, dreams were also characterized by increased negative emotions, which were particularly frequent in females, younger adults, and participants with poor sleep quality, nocturnal disruptive behaviours, anxiety and depressive symptoms. Conclusions: Our results confirm the hypothesis of a strong influence of the pandemic on dreaming, supporting both the hypothesis of continuity between wake and sleep mental processes and the view of a crucial influence of sleep quality and duration on dreaming activity

Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials

This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between "seen" trials and "not seen" trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expression, and written words). Results showed the typical visual ERP components in both "seen" and "not seen" trials. There was no statistical difference in the ERP peak latencies between the "seen" and "not seen" trials, suggesting a similar timing of the cortical neural synchronization regardless the primary visual consciousness. In contrast, ERP sources showed differences between "seen" and "not seen" trials. For the visuospatial stimuli, the primary consciousness was related to higher activity in dorsal occipital and parietal sources at about 400 ms post-stimulus. For the emotional face expressions, there was greater activity in parietal and frontal sources at about 180 ms post-stimulus. For the written letters, there was higher activity in occipital, parietal and temporal sources at about 230 ms post-stimulus. These results hint that primary visual consciousness is associated with an enhanced cortical neural synchronization having entirely different spatiotemporal characteristics as a function of the features of the visual stimuli and possibly, the relative qualia (i.e., visuospatial, face expression, and words). In this framework, the dorsal visual stream may be synchronized in association with the primary consciousness of visuospatial and emotional face contents. Analogously, both dorsal and ventral visual streams may be synchronized in association with the primary consciousness of linguistic contents. In this line of reasoning, the ensemble of the cortical neural networks underpinning the single visual features would constitute a sort of multi-dimensional palette of colors, shapes, regions of the visual field, movements, emotional face expressions, and words. The synchronization of one or more of these cortical neural networks, each with its peculiar timing, would produce the primary consciousness of one or more of the visual features of the scene

Relationship between cortical thickness and EEG alterations during sleep in the Alzheimer’s Disease

Recent evidence showed that EEG activity alterations that occur during sleep are associated with structural, age-related, changes in healthy aging brains, and predict age-related decline in memory performance. Alzheimer’s disease (AD) patients show specific EEG alterations during sleep associated with cognitive decline, including reduced sleep spindles during NREM sleep and EEG slowing during REM sleep. We investigated the relationship between these EEG sleep alterations and brain structure changes in a study of 23 AD patients who underwent polysomnographic recording of their undisturbed sleep and 1.5T MRI scans. Cortical thickness measures were correlated with EEG power in the sigma band during NREM sleep and with delta- and beta-power during REM sleep. Thinning in the right precuneus correlated with all the EEG indexes considered in this study. Frontal–central NREM sigma power showed an inverse correlation with thinning of the left entorhinal cortex. Increased delta activity at the frontopolar and temporal regions was significantly associated with atrophy in some temporal, parietal, and frontal cortices, and with mean thickness of the right hemisphere. Our findings revealed an association between sleep EEG alterations and the changes to AD patients’ brain structures. Findings also highlight possible compensatory processes involving the sources of frontal–central sleep spindles