To sleep, perchance to dream

A number of studies have previously noted that people with dementia tend to sleep less than those without dementia.  The question has been what is cause and what is effect?  Does getting less sleep promote the onset of dementia or does dementia disrupt sleep? The answer appears to be that both are true.

Sleep disorders are an almost universal problem with moderate and advanced dementia, especially for those with Alzheimer’s disease.  Alzheimer’s patients have trouble falling asleep and staying asleep.  The sleep wake cycle is often reversed with Alzheimer’s patients being awake an average of 40% of the time while lying in bed at night and then spending a significant part of the day asleep.  When awake at night, they may wander or yell out, disrupting the sleep of caregivers as well.  Sleep problems can be exacerbated by depression, restless leg syndrome and sleep apnea.

Some medications can also disrupt sleep. Cholinesterase inhibitors like Aricept (donepezil) are taken by many people with Alzheimer’s disease, but if taken at bed time they often cause vivid nightmares.  I experienced this myself within a few weeks of starting the medication and discovered that it is a well-recognized side effect.  Oddly the prescribing recommendations still call for dosing before bed, probably to minimize GI symptoms, but when I switched to taking it in the morning, I stopped having nightmares. A few days ago I got my medications mixed up and took the Aricept before bed instead of in the morning, and sure enough, I was chased throughout the night by gunmen trying to kill me.

So Alzheimer’s clearly disrupts sleep, but does lack of sleep affect the risk of getting Alzheimer’s? This has been surprisingly difficult to determine.  A report this week in Nature Communications provides the most compelling answer yet. The Whitehall II study was started in the 1980’s in the UK as a long-term investigation of various risk factors for a variety of diseases.  Nearly 8,000 subjects in this study were recruited when they were about fifty years of age and followed for up to thirty years. They were asked about nightly sleep duration when they were age fifty, and again when they were sixty and seventy. At age seventy, 6875 of these subjects were still alive and free of dementia.  Over the next seven years, 426 of these subjects developed dementia. Those who slept six or fewer hours each night at age fifty and sixty were about 30% more likely to develop dementia by the time they were seventy-seven than those who reported sleeping seven or more hours per night. The authors conclude “that short sleep duration in midlife is associated with the higher risk of dementia later in life, independently of sociodemographic, behavioral, cardiometabolic, and mental health factors.”

Why might getting adequate sleep be important in reducing risk of dementia, especially Alzheimer’s?  As I describe in Tattoo, a number of studies in animals and humans have suggested that amyloid and other toxins are removed from the brain during sleep by a fluid similar to cerebrospinal fluid (CSF). The flow of this cleansing fluid through the so-called glymphatic circulation of the brain is most active during non-REM slow wave sleep and is driven by a combination of brain electrical activity and arterial pulsations. 

Bottom line, getting adequate sleep during midlife is really important for reducing risk of dementia including Alzheimer’s disease.  Remember, the pathological changes of Alzheimer’s, especially the amyloid plaques, can start forming twenty years before there is any cognitive impairment. This is the time, when we are in our fifties and maybe even our forties, when it is especially important to get at least seven hours of sleep every night.