The Nocturnal Brain: Nightmares, Neuroscience, and the Secret World of Sleep

by Guy Leschziner

To some extent, having a tendency to want to wake up early and go to bed early, or wake up late and go to bed late, is normal. There is a broad spectrum of chronotypes — a person’s preference to go to sleep and wake up at a particular time. At the extremes of ‘morningness’ or ‘eveningness’ are those individuals known as ‘morning larks’ or ‘evening owls’. People with delayed sleep phase syndrome can be considered extremes of the extreme, ‘evening owls’ whose circadian rhythm is so delayed that it has negative consequences on their life. As with many features of our sleep, it appears that what chronotype we are is to some extent determined by our genes. Studies in twins or in families suggest that up to 50 per cent of our chronotype is under genetic control, and variants in the genes that regulate our circadian rhythm have been associated with both extreme ‘eveningness’ and extreme ‘morningness’. In a familial form of what’s known as ‘advanced sleep phase syndrome’, in which sufferers want to go to bed early in the evening and wake up extremely early in the morning, much rarer than delayed sleep phase syndrome, a mutation in one particular circadian gene, called ‘PER’, has been identified. Furthermore, mutations in another one of these circadian genes, called ‘DEC2’, seem to increase the amount of time we spend awake and reduce the amount of sleep required. For most people, however, it is not these few mutations that influence their wake/sleep pattern, but likely the cumulat...

So why should shift-workers have increased rates of certain cancers? One hypothesis is centred around the exposure to light at night. As we’ve discussed, light exposure at night suppresses the production of melatonin by the pineal gland, and it is argued that melatonin may have some anti-cancer activity above and beyond its role as a hormone — specifically, to absorb toxic by-products of oxygen metabolism that are thought to damage our DNA and predispose us to cancer. So, by regular exposure to light at night, perhaps we are lessening our resistance to cancer. This hypothesis is supported by the fact that people who are totally blind are less likely to develop breast cancer than normally sighted individuals, and in one experiment mutant mice predisposed to breast cancer were more likely to develop tumours when their circadian rhythms were disrupted. But there are lots of potential confounders.

These types of non-REM parasomnias represent a classical view of this condition, that people with this type of problem generally have no recollection at all of these events. But it is clear that Alex is certainly aware of some of his events. It is also clear that Alex is having dreams of a sort, despite me telling you that these phenomena emanate from non-REM sleep as opposed to REM or dreaming sleep. In fact, in recent years, we have begun to understand that previous notions of REM sleep being the stage of sleep exclusively in which we dream is not correct. It seems that dreaming in non-REM sleep is not unusual at all, although the content of the dreams is different.

As if that was not enough, it seems that sleep apnoea has other effects that compound the risk. While we know that sleep apnoea is strongly associated with obesity, it may be that sleep apnoea actually contributes to weight gain and related problems. The intermittent hypoxia that is a feature of sleep apnoea has been shown to fundamentally influence the effects of insulin, the hormone that controls the breakdown and storage of glucose that is crucial to the prevention of diabetes. Sleep apnoea lessens the body’s response to insulin, causing what is termed insulin resistance, the first step in the development of diabetes, and results in higher blood glucose levels.

Apart from the risk of stroke attributable to high blood pressure and blood vessel disease, sleep apnoea is also a risk factor for an irregular heart rhythm that can predispose clots to form in the heart, before shooting off to obstruct blood vessels in the brain. Sleep apnoea is also of relevance to headaches such as migraines and morning headaches, can result in increases in pressure inside the skull and can worsen the effects of Parkinson’s disease.

From the perspective of the general population, one of the most worrying, but also potentially exciting associations, is that of Alzheimer’s disease. While sleep apnoea appears to cause significant deterioration in various aspects of cognition, like attention, vigilance, long-term verbal and visual memory, reasoning and problem-solving, it may also have a direct role in the development of dementia. Sleep apnoea appears to hasten the development of cognitive impairment and Alzheimer’s, and treatment of sleep apnoea in Alzheimer’s causes an improvement in cognitive function. In the elderly, build-up of the protein beta-amyloid has been associated with sleep apnoea. This protein is deposited in the brain, forming plaques that cause signalling problems between neurones, triggering inflammation within the brain, and are one of the microscopic signatures of Alzheimer’s disease. And recently, an explanation for this association between sleep apnoea and dementia may have been forthcoming.

So, why do I refer to this association as exciting? Well, given how common both Alzheimer’s disease and sleep apnoea are, and increasingly so, some researchers have proposed that sleep apnoea is a major modifiable risk factor for Alzheimer’s. We cannot modify our genes (yet!), but if sleep apnoea is identified and treated at an early stage, could this be a preventative treatment for Alzheimer’s disease?

Patients with migraine will often experience word-finding difficulties, or tingling in their face or limbs, as the dysfunction of the aura spreads over their verbal or sensory areas. Many of us neurologists will have had to run down to the emergency department for an urgent stroke patient to find that the pattern of weakness is in keeping with hemiplegic migraine, where the dysfunction has affected the movement part of the brain. A few neurologists might even admit to having given clot-busting medication to patients who in hindsight were simply having a migraine attack! And for some people with migraine, the aura consists of symptoms associated with the brainstem — dizziness, imbalance, incoordination. But, as we know, the brainstem is also fundamental to the regulation of sleep and the maintenance of consciousness. In extreme cases, people have been reported going into a coma during migraine attacks.

It is incredibly common, when we meet after the sleep study, and I ask how they slept, to hear: ‘I slept terribly that night.’ But when we look at the sleep study, it shows a very decent night’s sleep — seven or more hours, with lots of deep sleep — despite the person in front of me being adamant that they only slept for an hour or two. This type of insomnia is termed ‘sleep state misperception’ or ‘paradoxical insomnia’, and is likely to explain why there is a huge overlap between the sleep studies of patients with insomnia and normal sleepers. Something about the way the person experiences sleep is different. Perhaps it is the quality of sleep, something we cannot gauge with our standard technique of measuring sleep, the polysomnogram. Or maybe it is as simple as the brain filling in time between the brief awakenings that are a feature of normal sleep, perceived as wakefulness by someone predisposed to this form of insomnia, rather than the deep sleep seen on the sleep study.