Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity

Mander, Bryce A.; Dave, Abhishek; Lui, Kitty; Sprecher, Katherine E; Berisha, Destiny; Chappel‐Farley, Miranda G.; Chen, Ivy Y.; Riedner, Brady A.; Heston, Margo B.; Suridjan, Ivonne; Kollmorgen, Gwendlyn; Zetterberg, Henrik; Blennow, Kaj; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Asthana, Sanjay; Johnson, Sterling C.; Bendlin, Barbara B.; Benca, Ruth M.

doi:10.1093/sleep/zsac135

Cited by 28 publications

(23 citation statements)

References 109 publications

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“…Furthermore, the microglia have attracted increasing attention from the medical scholars due to their complex phenotypes. Moreover, microglia are also closely related to the loss of synapses, tau phosphorylation, and poor memory, making these biological processes increasingly the centers of the study of neuroinflammation in AD (24).…”

Section: Neuroinflammation and Its Main Risk Factorsmentioning

confidence: 99%

“…The release of proinflammatory factors could be detected in the olfactory bulb (OB) of 2-month-old 5×FAD mice, showing significant microglial activation and morphological variations (132), suggesting that microglia-mediated OB neuroinflammation could serve as an early biomarker of AD. Even before the positive b-amyloid pathology is shown, the increased microglial activation is associated with defective NREM rapid-sleep spindle expression in the frontal cortex (24), providing evidence for the earlier diagnosis of AD. The restraint of microglia activation and the associated proinflammatory mediators are diagnostic and therapeutic targets of AD.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

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The effects of microglia-associated neuroinflammation on Alzheimer’s disease

et al. 2023

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Alzheimer’s disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the “amyloid cascade hypothesis” with the main focus of the pathological accretion of β-amyloid (Aβ) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aβ, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

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Section: Neuroinflammation and Its Main Risk Factorsmentioning

confidence: 99%

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

The effects of microglia-associated neuroinflammation on Alzheimer’s disease

et al. 2023

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“…EEG preprocessing was performed using semi-automated artifact rejection [41][42][43][44] with custom MATLAB (MathWorks, Inc, R2019b) scripts focusing on NREM sleep stages (N2 and N3 [N2N3]) with the EEGLAB toolbox (https://sccn.ucsd.edu/eeglab/index.php). 45 First, data were imported into EEGLAB and down sampled to 256Hz.…”

Section: Eeg Preprocessing and Slow Wave Spectral Analysismentioning

confidence: 99%

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Chappel-Farley,

Adams,

Betzel

et al. 2023

Preprint

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SUMMARYMemory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality—graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes—map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

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“…Sleep and the circadian system are important contributors to well-being and both physical and mental health [1][2][3][4]. Disruptions to sleep or the circadian clock in ill health may be a dellaMonica C_et_al_Manuscript.docx predictor of and/or contributor to disease progression as well having a negative impact on quality of life.…”

Section: The Need For Technology To Monitor Sleep and Circadian Rhyth...mentioning

confidence: 99%

“…In addition, the classification of sleep can be made at the simple sleep vs wake distinction to the more detailed macrostructure of the different stages of non-rapid eye movement sleep (NREM) stages N1 to N3 and REM sleep, and finally to the microstructure of the electroencephalogram (EEG) signal, as reflected in power spectral density or other EEG measures. From these different levels of measurements we can derive a range of parameters to describe sleep from self-reported sleep quality to the timing of sleep within the 24-h day, total sleep time (TST), sleep onset latency (SOL), wake after sleep dellaMonica C_et_al_Manuscript.docx onset (WASO), sleep efficiency (SE), spectral power of different EEG frequency bands, and individual EEG events such as slow waves and sleep spindles as well as their phase relationships (e.g., [2]).…”

Section: Gold Standard Assessments Of Sleep and Circadian Rhythms: Ad...mentioning

confidence: 99%

A protocol for evaluating digital technology for monitoring sleep and circadian rhythms in older people and people living with dementia in the community

della Monica,

Ravindran,

Atzori

et al. 2023

Preprint

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Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term monitoring of sleep and circadian rhythms in people living in the community may have great potential for early diagnosis, monitoring of disease progression and assessing the effectiveness of interventions in dementia and other health conditions. Many novel digital technology-based approaches for monitoring sleep and circadian rhythms, aimed at both the consumer and research markets, have recently become available. However, before such technology can be implemented at scale, its performance and acceptability need to be evaluated and compared to established gold standard methodology in relevant populations.Here we describe a protocol for the evaluation of novel sleep and circadian technology in cognitively intact older adults, some of whom have stable comorbidities, and in people living with dementia (PLWD). In this protocol a range of technologies is tested simultaneously first at-home during a one- to two-week period and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented.We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of sleep and circadian technology is best achieved in protocols in which sleep is mildly disturbed and in populations and settings that are relevant to the targeted use-case. We provide details on the design, implementation, and challenges of this sleep and circadian technology evaluation protocol along with examples of the datasets that have been generated in both cognitively intact older adults and PLWD. We place our protocol in the context of existing literature and highlight the benefits that our methodology has over previous approaches.Author SummarySleep and circadian (24-hour) rhythms are frequently disrupted in various physical and mental health conditions including dementia. These disturbances may merely be an outcome of the disease process or be drivers of disease progression. Either way, the ability to monitor sleep and circadian rhythms long-term and at-home could be highly beneficial for monitoring health status, early identification of decline, and implementation of interventions as well as monitoring the effectiveness of interventions. A number of new digital health technologies are now available that could allow non-invasive, non-intrusive, long-term monitoring of sleep and circadian rhythms at home. However, few of these have been evaluated against gold-standard measures in a relevant population. Here we describe our approach to simultaneously evaluating multiple types of sleep and circadian technologies against standard methodology, both at-home and in the laboratory, in a group of older adults with and without dementia. We discuss the feasibility of this protocol, provide examples of the data that were obtained, the data analyses and visualisations that can be applied, and explain the benefits of our approach.

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Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity

Cited by 28 publications

References 109 publications

The effects of microglia-associated neuroinflammation on Alzheimer’s disease

The effects of microglia-associated neuroinflammation on Alzheimer’s disease

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

A protocol for evaluating digital technology for monitoring sleep and circadian rhythms in older people and people living with dementia in the community

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