Impaired Prefrontal Sleep Spindle Regulation of Hippocampal-Dependent Learning in Older Adults

Mander, Bryce A.; Rao, Vikram; Lu, Bo; Saletin, Jared M.; Ancoli‐Israel, Sonia; Jagust, William J.; Walker, Matthew P.

doi:10.1093/cercor/bht188

Cited by 127 publications

(145 citation statements)

References 54 publications

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“…The disruption of sleep physiology by OSA is an underappreciated factor, which, together with hypoxemia and other already recognized factors, may further aggravate age-related memory deficits 15,16,19,76 . Clinically, this dynamic interplay also underscores numerous subjective and objective cognitive and emotional complaints in some patients 77,78 .…”

Section: Discussionmentioning

confidence: 99%

“…Studies reviewed here strongly suggest that tapping into the therapeutic potential of ischemic preconditioning, whilst working on ameliorating the acute and chronic effects of neuroinflammation, may offer legitimate new therapeutical targets in OSA 14,15,17,28,31 . Similarly, although they are in their infancy, studies of clinical approaches that target the sleep disturbance arm of this intricate equation advocate a significant future treatment intervention potential 14,16,76 .…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that, at a clinical level, improving SWA in older adults may represent a novel treatment for minimising cognitive decline in later life 19 . Similarly, it has been recently shown that older adults who express fewer prefrontal fast sleep spindles than younger adults, also exhibit a proportional impairment in hippocampal functioning during the subsequent wake periods, and with that impairment, a deficit in the ability to form new episodic memories 76 . Fast sleep spindles represent part of a coordinated nREM sleep-dependent memory mechanism, and it is thought that hippocampal sharp-wave ripples provide feedback excitation, which initiates neuroplasticity in spindle-activated cortical neurons 57 .…”

Section: -69mentioning

confidence: 94%

“…Fast sleep spindles represent part of a coordinated nREM sleep-dependent memory mechanism, and it is thought that hippocampal sharp-wave ripples provide feedback excitation, which initiates neuroplasticity in spindle-activated cortical neurons 57 . Relative to slow sleep spindles, fast sleep spindle events are associated with greater hippocampal activation and greater hippocampal-cortical functional connectivity 15,76 . Intriguingly, in a study of spindle frequency changes in OSA, it has been shown that OSA patients, unlike healthy controls, persisted in displaying a significant proportion of slow spindles in frontal, central and parietal regions during the night, perhaps suggesting that deregulated spindle formation might be another contributory facet to cognitive complaints in OSA patients 67 .…”

Section: -69mentioning

confidence: 99%

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Sleep apnoea and the brain: a complex relationship

Rosenzweig¹,

Glasser²,

Polšek³

et al. 2015

The Lancet Respiratory Medicine

216

211

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Summary (151/150 words)The complex relationship between obstructive sleep apnoea (OSA) and the brain is explored in this review. During the untreated apnoea/hypopnoea, intermittent hypoxia, reoxygenation and hyper/hypocapnia occur, in both adults and children, along with changes in cerebral blood flow and sleep fragmentation. They may in time result in cognitive deficits with functional consequences for work and school efficiency.The ability to assess how OSA affects cognition depends on the specificity and sensitivity of the tests, which are rarely developed specifically for OSA. In this review we discuss both the neural adaptive and maladaptive processes to hypoxemia. Their net result on cognitive and emotional performance depends on the stage of this dynamic process, effects on other body systems, cognitive reserve and the idiosyncratic susceptibility. The contribution of fragmented sleep and the disruption of sleep structure is also explored, with a focus on its effects at different times in the genesis of the disease. Lancet Respiratory Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: -69mentioning

confidence: 94%

Section: -69mentioning

confidence: 99%

See 2 more Smart Citations

Sleep apnoea and the brain: a complex relationship

Rosenzweig¹,

Glasser²,

Polšek³

et al. 2015

The Lancet Respiratory Medicine

216

211

View full text Add to dashboard Cite

show abstract

“…Spindle density, duration and amplitude decrease with age but the rate of decline is not the same in all subjects (Nicolas et al 2001;Crowley et al 2002;Guazzelli et al 1986;Wei et al 1999;Principe and Smith 1982). There is a correlation between age-related decline in spindle activity and decline in cognitive functioning (Peters et al 2008;Mander et al 2014). Sleep disruption by sleep-related disorders (e.g.…”

Section: Assessment Of Sleep Spindles and K Complexesmentioning

confidence: 99%

The case for using digital EEG analysis in clinical sleep medicine

Younes

2017

Sleep Science Practice

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Evaluation of sleep in clinical polysomnograms continues to rely almost exclusively on visual scoring that implements rules proposed by Rechtschaffen and Kales nearly 50 years ago. Apart from its cost and timeconsuming nature, visual scoring has limitations including: A) Sleep depth, which is a continuous variable, is treated as if it changes in a stepwise fashion from light (stage 1), to intermediate (stage 2) to deep (stage 3). B) Even with this limited scale, there is considerable inter-scorer variability, particularly in scoring stages 1 and 3 of non-REM sleep, thereby adding uncertainty to %time spent in these stages as a reliable metric for evaluating sleep depth. C) Limitation in scoring some of EEG features, including 1) arousal intensity, 2) extent of Alpha intrusion and 3) frequency, and characteristics of sleep spindles and K complexes. Digital analysis can solve these problems but producing a reliable system has been a challenge. In this review I begin with recent advances in digital scoring of sleep according to the Rechtschaffen and Kales rules and conclude that this technology has progressed enough to make it possible to obtain reliable, reproducible scoring, comparable in accuracy to scoring by highly experienced technologists, with minimal editing. This is followed by description of several new metrics that can be obtained if digital scoring systems were to be used routinely in clinical studies. The scientific evidence supporting the potential of these metrics to positively impact sleep medicine practice and the wide range of such metrics in patients studied in the sleep laboratory are highlighted.

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Evidence of neurodegeneration in obstructive sleep apnea: Relationship between obstructive sleep apnea and cognitive dysfunction in the elderly

Daulatzai

2015

J of Neuroscience Research

171

133

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The incidence of dementia and obstructive sleep apnea (OSA) increases with age. Late-onset Alzheimer's disease (AD) is an irreversible neurodegenerative disease of the elderly characterized by amyloid β (Aβ) plaques and neurofibrillary tangles. The disease involves widespread synaptic loss in the neocortex and the hippocampus. Rodent and clinical studies suggest that OSA impairs the structural integrity of several brain regions, including the medial temporal lobe. Indeed, hypoxia, hypertension, hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress noted in OSA patients also occur in AD patients. This Review highlights pathological commonality, showing that OSA upregulates Aβ, tau hyperphosphorylation, and synaptic dysfunction. Indeed, OSA and hypertension trigger hypoperfusion and hypometabolism of brain regions, including cortex and hippocampus. Several studies show that hypertension-driven brain damage and pathogenic mechanisms lead to an Aβ increase. The pathophysiological mechanism by which OSA enhances hypertension may be linked to sympathoexcitation, oxidative stress, and endothelial dysfunction. Strong pathophysiological similarities that exist between OSA and AD are underscored here. For example, the hippocampus is negatively impacted in both OSA and AD. OSA promotes hippocampal atrophy, which is associated with memory impairment. Cognitive impairment, even in the absence of manifest dementia, is an important independent predictor of mortality. However, several pathophysiological mechanisms in OSA are reversible with appropriate therapy. OSA, therefore, is a modifiable risk factor of cognitive dysfunction, and treating OSA prior to mild cognitive impairment may be an effective prevention strategy to reduce risk for cognitive decline and AD in middle-aged persons and the elderly.

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Impaired Prefrontal Sleep Spindle Regulation of Hippocampal-Dependent Learning in Older Adults

Cited by 127 publications

References 54 publications

Sleep apnoea and the brain: a complex relationship

Sleep apnoea and the brain: a complex relationship

The case for using digital EEG analysis in clinical sleep medicine

Evidence of neurodegeneration in obstructive sleep apnea: Relationship between obstructive sleep apnea and cognitive dysfunction in the elderly

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