Sleep-Based Interventions in Alzheimer’s Disease: Promising Approaches from Prevention to Treatment along the Disease Trajectory

Abstract

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.

Current Alzheimer disease research highlights: evidence for novel risk factors

“…[ 25 ] Since medications might further impair cognition, non-pharmacological interventions are of particular interest for older adults who are at high risk for dementia. Cordone et al [ 26 ] highlighted several promising techniques to enhance NREM sleep oscillations that have solid scientific basis for preventing or slowing down AD pathology but remain to be tested in clinical settings.…”

Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer’s Disease

“…Several authors have discussed the association between sleep and the pathogenesis of AD via Aβ and other factors like Tauprotein; and some have proposed sleep interventions to reduce AD symptoms (Cordone et al, 2019(Cordone et al, , 2021Wang and Holtzman, 2020;Özcan et al, 2020).…”

“…prone society. As well as obesity prevention, interventions associated with sleep quality should be proposed as a strategy to reduce AD symptoms (Cordone et al, 2019(Cordone et al, , 2021. Special interest has been placed in sleep hygiene to improve the quality of sleep.…”

“…Special interest has been placed in sleep hygiene to improve the quality of sleep. In this way, it is suggested to avoid the use of psychoactive substances at night (Cordone et al, 2021) such as caffeine (Roehrs and Roth, 2008), energy drinks (Sampasa-Kanyinga et al, 2018), andsmoking (McNamara et al, 2014). Conversely, there are various drugs that are used to treat sleep deficiency in AD patients.…”

Relationship between Cortical Thickness and EEG Alterations during Sleep in the Alzheimer’s Disease

“…In general, sleep seems to be a privileged physiological state for beta-amyloid clearance [ 1 , 2 ], while waking hours are characterized by progressive beta-amyloid deposition as a function of the time spent awake [ 3 , 4 , 5 ]. Sleep disturbances affect many patients with AD from the prodromal stage onwards [ 6 , 7 , 8 , 9 ]. Therefore, it has been hypothesized that the initial neurodegenerative processes of AD could alter sleep dynamics and that sleep disruptions could, in turn, increase beta-amyloid burden and establish a vicious circle that negatively impacts the neurodegenerative process [ 10 ].…”