Abstract
Even prior to the onset of the prodromal stages of Alzheimer’s disease (AD), a constellation of sleep disturbances are apparent. A series of epidemiological studies indicate that multiple forms of these sleep disturbances are associated with increased risk for developing mild cognitive impairment (MCI) and AD, even triggering disease onset at an earlier age. Through the combination of causal manipulation studies in humans and rodents, as well as targeted examination of sleep disturbance with respect to AD biomarkers, mechanisms linking sleep disturbance to AD are beginning to emerge. In this review, we explore recent evidence linking local deficits in brain oscillatory function during sleep with local AD pathological burden and circuit-level dysfunction and degeneration. In short, three deficits in the local expression of sleep oscillations have been identified in relation to AD pathophysiology: (1) frequency-specific frontal deficits in slow wave expression during non-rapid eye movement (NREM) sleep, (2) deficits in parietal sleep spindle expression, and (3) deficits in the quality of electroencephalographic (EEG) desynchrony characteristic of REM sleep. These deficits are noteworthy since they differ from that seen in normal aging, indicating the potential presence of an abnormal aging process. How each of these are associated with β-amyloid (Aβ) and tau pathology, as well as neurodegeneration of circuits sensitive to AD pathophysiology, are examined in the present review, with a focus on the role of dysfunction within fronto-hippocampal and subcortical sleep-wake circuits. It is hypothesized that each of these local sleep deficits arise from distinct network-specific dysfunctions driven by regionally-specific accumulation of AD pathologies, as well as their associated neurodegeneration. Overall, the evolution of these local sleep deficits offer unique windows into the circuit-specific progression of distinct AD pathophysiological processes prior to AD onset, as well as their impact on brain function. This includes the potential erosion of sleep-dependent memory mechanisms, which may contribute to memory decline in AD. This review closes with a discussion of the remaining critical knowledge gaps and implications of this work for future mechanistic studies and studies implementing sleep-based treatment interventions.
Highlights
Both macro and micro features of sleep architecture change across the adult lifespan, and the individual variability in the magnitude of change appears to be associated with the degree of cognitive decline and the severity of risk for dementias such as Alzheimer’s disease (AD) (Ohayon et al, 2004; Redline et al, 2004; Yaffe et al, 2011; Lim et al, 2013a,b; Spira et al, 2013; Lo et al, 2014; Mander et al, 2015, 2016, 2017a; Osorio et al, 2015; Song et al, 2015; Sprecher et al, 2015, 2017; Chen et al, 2016; Bubu et al, 2017, 2019; Kabeshita et al, 2017; Pase et al, 2017; Shi et al, 2017; Tsapanou et al, 2017; Lutsey et al, 2018)
Some evidence indicates that this effect of Aβ burden on local sleep may be specific to slow wave expression, as it does not appear to be associated with the REM sleep and spindle deficits observed in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (Brazete et al, 2013, 2016; Mander et al, 2015; Brayet et al, 2016; Gorgoni et al, 2016; Winer et al, 2019)
In addition to sleep deficits impacting tau pathology, more recent work shows that tau burden may be related to a number of distinct global and local sleep deficits observed in MCI and AD, each of which likely depends on the location of tau accumulation
Summary
Both macro and micro features of sleep architecture change across the adult lifespan, and the individual variability in the magnitude of change appears to be associated with the degree of cognitive decline and the severity of risk for dementias such as Alzheimer’s disease (AD) (Ohayon et al, 2004; Redline et al, 2004; Yaffe et al, 2011; Lim et al, 2013a,b; Spira et al, 2013; Lo et al, 2014; Mander et al, 2015, 2016, 2017a; Osorio et al, 2015; Song et al, 2015; Sprecher et al, 2015, 2017; Chen et al, 2016; Bubu et al, 2017, 2019; Kabeshita et al, 2017; Pase et al, 2017; Shi et al, 2017; Tsapanou et al, 2017; Lutsey et al, 2018). Some evidence indicates that this effect of Aβ burden on local sleep may be specific to slow wave expression, as it does not appear to be associated with the REM sleep and spindle deficits observed in MCI and AD (Brazete et al, 2013, 2016; Mander et al, 2015; Brayet et al, 2016; Gorgoni et al, 2016; Winer et al, 2019).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
