Sleep essentialism

Sleep is the most idiotic of all behaviours. When you are asleep, you cannot forage for food or eat. You cannot find a mate. You cannot reproduce. You cannot care for your offspring. Worse still, you are vulnerable to predation. On any one of these grounds, but especially all of them as a collective, there ought to have been a powerful evolutionary pressure to block the emergence of sleep or anything remotely like it. But sleep did emerge. And it persisted. Indeed, it has been said that if sleep does not serve an absolutely vital function, then it is the biggest mistake the evolutionary process has ever made. Prior to the discovery of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages some 70 years ago, we still wondered whether evolution had made such an error. Science and medicine remained perplexed by the simplest of questions, ‘Why do we sleep?’ One crass response at the time was that we sleep to cure sleepiness. That is the fatuous equivalent of saying that we eat to cure hunger. It tells us little about the biological benefits of nutrition. Now, 70 years later, we recognize that Mother Nature did not commit a spectacular blunder in creating this thing called sleep. So much so that we have had to upend the question: are there any major physiological systems within the body, or core operations of the brain, that are not enhanced by sleep when we get it, or impaired when we do not get enough? The answer seems to be no. For example, several nights of just 4 h of sleep in otherwise healthy individuals impairs blood sugar regulation to such an extent that you would be classified as pre-diabetic.1 The immune system follows a similar profile of impairment. Individuals reporting less than 7 h of sleep a night are almost three times more likely to become infected by a rhinovirus.2 In a prospective study, women sleeping 5 h or less had a 70% greater likelihood of developing pneumonia across a 4-year period.3 Individuals sleeping less than 5 h a night in the week before receiving a flu shot produced less than 50% of the normal antibody response, relative to having had a full 8-h sleep opportunity.1 Hormonal systems suffer, too.1 Healthy young males sleeping just 4 h a night for four nights will have a level of testosterone equivalent to that of someone 10 years their senior. That is, insufficient sleep ‘ages’ a man by over a decade in terms of sex-hormone virility. Women sleeping less than 8 h have a 17% reduction in follicular-stimulating hormone,4 are 30% more likely to have abnormal menstrual cycles, and may have reduced fertility, relative to those obtaining sufficient sleep. Flaming June by Frederic Leighton, 1st Baron Leighton. Public domain, via Wikimedia Commons. Flaming June by Frederic Leighton, 1st Baron Leighton. Public domain, via Wikimedia Commons. A loss of sleep, even of just 1 h, can be heartbreaking. Case in point is the global experiment performed on more than 1.5 billion people across 70 countries twice a year, called Daylight Saving Time. In the spring, when adjusting the clocks means we lose 1 h of sleep, a small observational study noted a 24% increase in heart attacks the following day.5 In the autumn, when we gain an hour of sleep opportunity, there was a 21% decrease in heart attacks. A similar pattern is observed for suicide rates, road traffic accidents, even hospital admission rates, especially in the direction of lost sleep in the spring. Sleep essentialism. Sleep essentialism. Benevolent as sleep is for the body, the brain receives arguably the most extraordinary enrichment from slumber.6 Sleep before learning prepares the brain, and specifically the hippocampus, for the initial encoding of new memories. Sleep after learning supports the subsequent offline consolidation of those memories, decreasing the likelihood of forgetting. Neurophysiology and neuroimaging studies have revealed an elegant underlying mechanism. Here, coordinated neural oscillations in the hippocampus (sharp-wave ripples) and the cortex (slow waves and sleep spindles) transact a near file-transfer process, shifting memory representations from the short-term repository of the hippocampus to the neocortex. Sleep further dispenses a form of mental first aid.6 Deep NREM sleep provides an overnight, anxiolytic benefit, downscaling levels of anxiety. Conversely, there is a dose-response relationship between insufficient sleep and escalating anxiety, in part due to a functional disconnection between the medial prefrontal cortex and amygdala.7 In compliment, REM sleep services a form of overnight therapy, helping dissipate the painful sting from difficult or even traumatic emotional experiences. As E. Joseph Cossman once said, ‘the best bridge between despair and hope is a good night of sleep’. It is perhaps no surprise that we have yet to discover a single major psychiatric condition in which sleep is normal. Yet it is in the realm of Alzheimer’s disease that some of the most recent and scintillating sleep discoveries have been made.8 Epidemiological associations offered the first clues, demonstrating that those individuals who report sleeping less than 6 h a night have significantly greater amyloid-β burden in later life, relative to those sleeping more than 7 h. Individuals with sleep disorders such as insomnia and sleep apnoea show a similarly increased rate of amyloid-β accumulation, as well as higher rates of Alzheimer’s disease and faster cognitive decline. Correlation then went in search of causation. Humans deprived of sleep for a single night, or even just selectively deprived of deep NREM sleep across one night, show a significant increase in amyloid-β levels the following day, indexed in CSF markers, PET scans, and also circulating blood markers. Similar findings are starting to emerge for tau protein. If sleep loss causally triggers a next-day increase in Alzheimer’s disease-related proteins, then what is it about sleep when we do get it that averts such accumulation? The answer came from a seminal discovery in mice, which revealed the brain’s equivalent of the body’s lymphatic system, called the glymphatic system.8 Although active to some degree during wakefulness, this ‘brain cleansing’ mechanism switches to high-flow mode during NREM sleep. Among the metabolic detritus that the glymphatic system removes from the brain each night are amyloid-β and tau. That is, the glymphatic system provides a sleep-dependent mechanism that may aid in the elimination of Alzheimer’s disease pathology. ‘Goodnight, sleep clean’, has been the tagline. Without sufficient sleep each night, the pathology escalates, like compounding interest on a loan, helping to explain the aforementioned epidemiological data linking insufficient sleep to Alzheimer’s disease. Disheartening as this news may be, there is a silver lining. Unlike many of the other factors contributing to ageing and Alzheimer’s disease, sleep is a modifiable treatment target. We may be able to do something about it, and early on, too. With newly emerging technology that can enhance deep sleep quality in people in ‘midlife’ (when sleep begins to decline perniciously), such as electrical brain stimulation or efficacious cognitive behavioural therapy for insomnia, could we help bend the arrow of Alzheimer’s risk down on itself? In doing so, could we move from a model of late-stage treatment to that of midlife prevention? Most recently, we and others have reported that sleep provides a non-invasive, potentially scalable, and repeatable biomarker of amyloid-β and tau burden within the living human brain. That is, nested within the physiological static of sleep at night, there are unique ‘dents’ in the electrical brainwave activity of NREM sleep that can forecast Alzheimer’s disease pathology risk years in advance. Disordered electrical sleep quality in midlife may therefore be a predictive ‘canary in a coal mine’ when it comes to Alzheimer’s disease risk later in life. Taking a step back, and considering this broad constellation of night-time benefits for brain and body, I have come to change my fundamental conception of sleep’s birth. We assume that sleep evolved. I am enamoured with an opposite, heterodox view. What if we started asleep, and it was from sleep that wakefulness emerged, not the other way around? Sleep as the de facto state. Shy of a time capsule, I will likely never know. However, sleep is evidently universal. Invertebrates, such as molluscs and echinoderms, and even very primitive worms, enjoy periods of slumber (delightfully called ‘lethargus’). How ancient does this make sleep? Worms emerged during the Cambrian period 500 million years ago, meaning that sleep predates vertebrate life. Sleep, it seems, evolved with life itself on this planet. And thereafter perhaps, came the gift of wakefulness? Speculative theories aside, of one thing I do feel more certain than ever: sleep appears to be obligate, non-negotiable. Sleep essentialism. Matthew Walker is Professor of Neuroscience and Psychology at the University of California, Berkeley, USA, and author of Why We Sleep (Penguin Random House).