Could your chronic tiredness be a sign of a silent killer?




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Nothing is more guaranteed to sink the heart of the doctor opening a patient’s notes than seeing the acronym TATT, which stands for ‘tired all the time’. 

For the list of possible causes of TATT is almost endless: underactive thyroid gland, diabetes, depression, cancer, shift work, anaemia, carbon monoxide poisoning… the list goes on.

It is also incredibly common. Working out if there’s a serious underlying issue can be like looking for a needle in a haystack. 

One possible — if under-considered — explanation is sleep apnoea. This is a sleep disorder in which someone briefly, but repeatedly, stops breathing during the night. 

Did you know? Over time, sleep apnoea has serious consequences for health, including an increased risk of stroke and heart disease - for both men and women

Did you know? Over time, sleep apnoea has serious consequences for health, including an increased risk of stroke and heart disease - for both men and women

Did you know? Over time, sleep apnoea has serious consequences for health, including an increased risk of stroke and heart disease – for both men and women

Unsurprisingly, this disturbs sleep, although the person may not realise it — and over time, sleep apnoea has serious consequences for health, including an increased risk of stroke and heart disease.

In fact, we are living through a sleep apnoea epidemic. A recent Swiss study suggests that up to one in two men and one in four women has problems with their breathing at night.

Maria was one of them.

When I met Maria, a woman in her 40s who’d been referred to our sleep clinic, I imagined that TATT has been scrawled in her medical notes by her GP.

Juggling motherhood and a challenging job in healthcare, she told me: ‘I was exhausted all the time. I never felt well and thought maybe it was my thyroid or anaemia. I went to the doctor repeatedly for blood tests.’

Sheer exhaustion was impacting on all aspects of her life. She had developed eczema — after a lifetime of clear skin — and was struggling to shift a little extra weight. Exercising felt impossible.

Simple steps to end the curse of restless leg  

The history of medicine is littered with diagnoses that have not been formally accepted or are believed to have been made up by pharma companies. Restless legs syndrome (RLS) is one such condition.

To any doubters, though, I would invite them to visit my clinic.

RLS causes a terrible urge to move, often accompanied by such sensations as tingling, buzzing, pain or cramping.

One patient said it is ‘like having bees buzzing inside the skin of your legs’. Symptoms get worse at night, making it impossible to get to sleep.

There are two types of leg movements: some are semi-voluntary, an effort to obtain relief from the torture of their sensations; but there are also involuntary kicks and twitches of the legs that occur deep in sleep — perhaps one of the first pieces of evidence that this is a real condition.

Monitoring brainwave activity during the night confirms that patients are asleep during these kicks. But these periodic limb movements, as they’re known, add insult to injury.

Not only do sufferers experience symptoms that stop them dozing off, but once they finally do, they can wake them up again.

There is also evidence that RLS, like sleep apnoea, is associated with an increased risk of cardiovascular disease, high blood pressure and stroke.

Studies have suggested it affects roughly one in 20 adults, many of whom go years without a proper diagnosis. In some people, pain may be the predominant symptom, which means RLS can be misdiagnosed as cramps, varicose veins or nerve problems.

But there are some key clues. The first is that people rarely experience symptoms in the morning. The second is that movement provides relief.

Despite the name, I have also seen cases of restless arms, restless abdomens, and even a few cases of restless genitals.

We don’t know what causes RLS, but think it is linked to low iron levels. It seems to be more common in people with iron deficiency. Medications that increase levels of dopamine (a neurotransmitter) in the brain can provide relief.

However, they can also worsen the symptoms. Instead, minor lifestyle changes such as a reduction in caffeine, tobacco and alcohol can often suffice.

Sleep deprivation also worsens RLS, and so a regular sleep pattern can help.

It was also having a significant effect on her relationship with her husband. ‘Any little bump in the road was like the worst thing that had happened to anybody ever, and I’d fly off the handle,’ she explained. ‘I’m quite a cheery person by nature but my sense of humour went.’

Fuelled by coffee, Maria would pinch herself under the table in meetings to make sure she didn’t doze off. If she wasn’t working, she would take her children to school, then go back to bed, setting her alarm for 20 minutes before she had to pick them up again.

‘I didn’t even have the energy to read a book because I’d be asleep before I got to the end of the page,’ she told me. ‘I really did feel like I was falling apart.’

As I listened, I was struck by the lengths that Maria went to in an attempt to improve matters. ‘I was doing everything I could,’ she said. ‘I was trying meditation, yoga, mindfulness, I was trying to change my diet. I even changed my job.’

It was 18 months before sleep apnoea was considered. That’s when she was sent to our clinic at Guy’s Hospital.

Normally, as you drift off, the countless small muscles of the walls of your airway slacken a little. However, if your airway is narrow enough or becomes sufficiently floppy, it can become partly or completely obstructed.

PATIENTS STOP BREATHING 

This collapse results in oxygen levels falling and the heart rate increasing, disrupting your sleep in order for muscle tone to return briefly to the airway, allowing you to breathe again.

This can happen ten, 20 or even, in rare cases, 100 times an hour.

The rates of sleep apnoea have increased in parallel with our girths and neck circumferences. Fat around the neck makes the airway narrower and more likely to collapse, while fat on the chest increases the effort of breathing.

But obesity is not the only cause of sleep apnoea. It may run in families and is often related to the shape of the airway. A large tongue, recessed lower jaw and large tonsils can cause a narrowing, too.

It also appears to be more common in people of South-East Asian ancestry. It is more common, too, in older people, possibly because changes to muscle as we age mean the airway is more likely to collapse in on itself.

Snoring can be a warning sign, but it is not just a snoring problem. Having your sleep disrupted several times an hour, results — unsurprisingly — in excessive sleepiness during the day.

This sleepiness can be extreme. At our centre, we’ve had countless patients whose sleep apnoea has come to light after they have fallen asleep at the wheel of their car and had an accident. Indeed, having sleep apnoea increases the risk of a accident by two or three times.

DANGER MISSED BY DOCTORS 

Sleep apnoea has costs beyond tiredness. With each obstruction and brief suffocation, there is a surge of noradrenaline (a stimulating hormone), a rise in heart rate and blood pressure, a stiffening of the arteries and a drop in oxygen levels.

With each pause in breathing, changes to blood flow back to the heart result in altered levels of a hormone called ANP, which means the kidneys continue to produce more urine than they otherwise would at night. 

This results in more frequent nocturnal urination.

Fact: Sleep apnoea also influences the levels of two hormones called leptin and ghrelin, important for the regulation of appetite and metabolism.

Fact: Sleep apnoea also influences the levels of two hormones called leptin and ghrelin, important for the regulation of appetite and metabolism.

Fact: Sleep apnoea also influences the levels of two hormones called leptin and ghrelin, important for the regulation of appetite and metabolism.

Are sleep problems making you fat? 

While we know that sleep apnoea is strongly associated with obesity, it may also be that sleep apnoea actually contributes to weight gain.

The brief drops in oxygen levels have been shown to lessen the body’s response to insulin, the hormone that controls the breakdown and storage of glucose (the sugar in our blood).

This causes insulin resistance, the first step in the development of diabetes.

Sleep apnoea also influences the levels of two hormones called leptin and ghrelin, important for the regulation of appetite and metabolism.

So it may be that sleep apnoea in itself increases calorie intake and how those calories are processed, predisposing to further weight gain.

Over time, these physiological changes can lead to permanently high blood pressure and, in turn, the serious problems it causes such as heart disease and stroke.

There is also a link with short-term cognition problems, such as concentration, and possibly long-term with Alzheimer’s disease (see panel, far right).

While high blood pressure is one of the largest risk factors for cardio- vascular disease and stroke, there seem to be additional effects of having sleep apnoea that may play a part. Experimental research into recurrent drops in oxygen suggests that these fluctuations can cause the thin lining of the blood vessels to stop working as it should.

Known as the endothelium, this lining has an important function: it detects changes in blood flow and releases substances that regulate the size and thickness of blood vessels in response. Dysfunction of the lining is considered an early stage of cardiovascular disease.

Maria was only diagnosed with sleep apnoea by chance. She recalled it vividly: ‘I was at the doctor’s for something else, and an information video came on the screen in the waiting room describing some symptoms. I went in to see my GP and said: “I think I’ve got sleep apnoea.” ’

It was at this point she was referred to our centre. A piece of kit she was given to wear at home at night to monitor her breathing, heart rate and oxygen levels then revealed that her oxygen levels were dipping an alarming 86 times every hour over the course of the whole night.

The tell-tale signs had been there. Maria was a snorer — loud enough for her husband regularly to seek sanctuary in their toddler’s bedroom. She had also been getting up three or four times a night to go to the loo.

She said: ‘Although doctors asked if I was sleeping OK — which technically I did, for as soon as my head hit the pillow I was out — they didn’t delve into me getting up frequently in the night, or anything like that.’

The problem may have been that Maria didn’t fit the traditional mould for sleep apnoea. She wasn’t elderly, she hadn’t got a particularly large neck and she wasn’t obese. Also, the problem is more common in men. Sleep physicians do, however, see people of normal weight who stop breathing an astounding number of times a night.

CAN A TONGUE ZAPPER HELP?

There are various treatments for sleep apnoea. Weight loss helps, and for some patients options include not sleeping on their back and oral devices to hold the lower jaw forward and open up the airway.

Symptoms to watch for 

As many as 3.9 million people in the UK have sleep apnoea, according to the Sleep Apnoea Trust, with many of them going undiagnosed. How can you tell if you might be one of them? These symptoms are characteristic of the condition:

Loud snoring

Waking up frequently in the night to go to the toilet

Night sweats

Periods during the night where breathing stops — followed by gasping or snorting

Daytime sleepiness — specifically nodding off or struggling to stay awake in front of the TV, when reading or when traffic stops for a few minutes

More recently, for very serious cases, an electronic device can be implanted in the neck to stimulate the nerve that retracts the tongue in sleep. At the time, however, there was really only one choice for Maria — CPAP, or continuous positive airway pressure. This device consists of a face mask attached to a small machine that pumps out pressurised air that keeps the airway open during sleep.

Benefits of CPAP on cognitive functioning, mood and sleepiness have clearly been demonstrated. We also know that CPAP results in an improvement in blood pressure and the function of the endothelium.

The research is less clear on whether it can reduce the risk of longer-term problems such as the risk of stroke or heart disease.

While many patients find it hard to stick with using the mask, Maria persisted.

No longer short-tempered and exhausted, Maria was smiley and energetic and she told me her sleepiness had totally resolved. ‘I don’t love the mask,’ she said. ‘But the effect it has had on my life has been so positive.

‘I used to come home, switch on the TV and be asleep within half an hour, but now I can focus.’ 

Dr Guy Leschziner is a consultant neurologist and sleep physician at Guy’s Hospital in London. Adapted from The Nocturnal Brain: Tales Of Nightmares And Neuroscience by Dr Guy Leschziner, Simon & Schuster, £16.99. To order a copy for £13.59, visit mailshop.co.uk/books or call 0844 571 0640. p&p is free on orders over £15. Spend £30 on books and get FREE premium delivery. Offer valid until March 19, 2019.

WHY SLEEPING WELL CAN KEEP DEMENTIA AT BAY… 

Deep sleep, in particular, seems important for the brain’s housekeeping work

Deep sleep, in particular, seems important for the brain’s housekeeping work

Deep sleep, in particular, seems important for the brain’s housekeeping work

When I was at medical school, we were taught about the lymphatic system — a series of channels within the body that drain fluid from the tissues back into the circulation. Roughly three litres of fluid pass through this system each day, helping to remove waste substances and toxins.

At the time, we were told that the one organ that did not have a lymphatic system was the brain.

But, in the past few years — and it is remarkable that it is so recent — it’s been discovered that in fact there is a network of tiny channels in the brain, that have been termed the glymphatic system.

These act like a waste disposal chute for the brain, and there is clear evidence that one of the substances cleared by this network is the protein beta-amyloid.

A build-up of this compound is one of the characteristics of Alzheimer’s disease. The protein forms plaques that cause signalling problems between nerve cells in the brain, triggering inflammation.

But what has this to do with sleep? Well, evidence from sleeping or anaesthetised mice shows that the channels of the glymphatic system expand during sleep, and the flow of fluid through this network increases.

In humans, levels of beta-amyloid in the cerebrospinal fluid found in the brain and spinal cord, where the fluid inside the glymphatic vessels ends up, are highest in the morning, suggesting a similar flushing-out.

In fact, a recent study in humans has shown that after even a single night of sleep deprivation, levels of beta-amyloid in certain parts of the brain, including the hippocampus (which is involved in both short and long-term memory, and which is often damaged in Alzheimer’s) go up.

So sleep deprivation could well carry an increased risk for Alzheimer’s disease. Deep sleep, in particular, seems to be important for the brain’s housekeeping work.

In deep sleep, the glymphatic channels open up by up to 60 per cent, thereby allowing the carriage of potentially toxic substances such as beta-amyloid away from the brain.

This may go some way to explain why sleep apnoea not only appears to cause significant deterioration in various aspects of cognition, such as attention, reasoning and problem-solving, but may also have a direct role in the development of dementia.

In the elderly, a build-up of beta-amyloid has been associated with sleep apnoea, and treating sleep apnoea in those with Alzheimer’s seems to improve cognition.

If you consider that in sleep apnoea, sleep is disrupted, sometimes hundreds of times per night, it is easy to understand why this might impair the functioning of the glymphatic system, why beta-amyloid levels in the brain might go up, and why this might predispose to Alzheimer’s.

The reality of this association between poor sleep and Alzheimer’s is yet to be fully unravelled. In fact, there is an alternative explanation: many degenerative disorders of the brain result in subtle changes years or even decades before symptoms become more obvious.

It may be that in Alzheimer’s, early changes to the biochemical pathways in the brain years before memory deteriorates result in worsening sleep. In other words, it may be that the poor sleep is not the cause of Alzheimer’s but the result of the very early stages of the disease.

Indeed, this may be a possible explanation for why many older hypnotic drugs that used to be the mainstay for insomnia — particularly benzodiazepines — have been found to increase the risk of subsequent dementia.

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. If sleep apnoea is identified and treated at an early stage, could this be a preventative treatment for Alzheimer’s?

 



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