As we all know, sleep plays a critical role in brain functioning. One such function is memory, with sleep enhancing memory encoding and consolidation. Unsurprisingly, study participants deprived of sleep for 36 hours had significantly worse memory retention and poorer insight into their performance than participants who slept regularly, and administration of caffeine to overcome the decreased alertness was incapable of improving memory function in a sleep deprived sub-group. Another study, utilizing fMRI imaging, showed that sleep deprived participants had decreased activation of the medial temporal lobe in a verbal learning task, but increased prefrontal and parietal lobe activity (presumably to compensate for decreased temporal function) and a corresponding 40% decrease in memory formation of the target words. These results showcase the important role that sleep plays in memory formation, but studies within the last decade have suggested there may be an even more powerful impact on cognition.
Insomnia is a common complaint amongst patients with neurodegenerative diseases, and was long thought to be a symptom of these disorders. More recently, however, there has been interest in how insomnia might actually be a risk factor for neurodegeneration in a bidirectional relationship. In a study following participants with and without insomnia for 6 years, those in the 90th percentile of sleep fragmentation were 1.5 times more likely to develop Alzheimer’s disease (AD) compared to those in the 10th percentile of sleep fragmentation (representing longer and deeper sleep). Another study, performed over 40 years, showed that patients with complaints of insomnia had a 33% increase in risk for dementia and a 51% increase in risk for AD. Furthermore, a PET imaging study showed that a single night of sleep deprivation significantly increased amyloid-beta deposition (Aβ), even in healthy controls. Results like these promoted further research into the link between insomnia and neurodegeneration providing insight into the neurophysiological effects of sleep.
This raises the question; How exactly does sleep prevent Aβ buildup and reduce risk for AD and dementia?
As you may already know, the brain is contained within a closed cavity, and because of this, any change in volume (such as an influx of blood) will create either a change in pressure or a change in volume of something else (such as cerebrospinal fluid or CSF). Recent studies have been testing these fluid dynamics and how they might play a role in the clearance of toxic by-products such as Aβ. One such study, utilizing blood oxygen level-dependent (BOLD) fMRI imaging and EEG measurement of neural activity found a distinct pattern of fluid flow during slow-wave sleep (SWS) also known as non-rapid eye movement (NREM) sleep. Specifically, it seems that during SWS, a decrease in neural activity also creates a decrease in cranial blood flow. Slow pulses of blood during this phase of sleep are inversely correlated to CSF flow, meaning that as blood flows into the cranial cavity, CSF flows out, and vice versa, in a pulsatile fashion. Because of these pulses of blood flow, waves of CSF are first moved around the brain, mixing with interstitial fluid and taking up toxic by-products, and are then pushed out, effectively clearing toxins from the cranial cavity. In this way, SWS is crucial for neuronal health as this is the only time that hemodynamic flow is coupled with the “bathing” action of CSF. Another related function is proteostasis, the maintenance of healthy proteins and clearance of misfolded proteins. In mice, sleep deprivation impairs proteostasis and causes brain cell death.
These studies show that lack of sleep contributes to neurodegeneration, but neurodegenerative disorders also contribute to impaired sleep. This bidirectional pathway of toxic protein accumulation causes neurodegeneration that in turn furthers sleep impairment in a repetitive cycle. Thus treatment of sleep disorders is just as important as treatment of cognitive decline in AD patients; sweet dreams!