By Mitchell G. Miglis, M.D.
A 43-year-old businessman arrives at the sleep clinic for his first appointment. He tells the physician that he falls asleep easily — in fact, he’s out before his wife can turn off the light — however, he feels that his sleep is restless, and he often wakes up unrefreshed. He pushes through the day and struggles to stay awake during meetings. Most concerning of all is the decline he’s noticed in his memory and ability to concentrate. Simple tasks require a renewed focus to complete, and his friends have commented on his inability to remember certain details from their conversations. He describes a sensation of sleepwalking through his waking state, as if he’s living in a constant fog.
The association between sleep deprivation and cognitive impairment is nothing new. In fact, it is something we have all experienced. It only takes one poor night’s sleep for us to notice that our reaction time slows, concentration requires more effort, and our ability to form new memories is impaired. For those of us in the medical profession, we can all relate to long nights of hospital call and the feeling at 3 a.m. or 4 a.m. as if we were wading through a form of intellectual molasses. Fortunately, new work-hour requirements have limited this practice in medical training, as they have in the aviation and transportation industry.
It has been well established by now that sleep is integral to memory formation. Researchers have demonstrated that sleep-deprived students perform poorly on memory-specific tasks (1). More interestingly, they have also shown that students allowed to nap after learning new material have greater recall than students who followed healthy, non-sleep restricted patterns but did not nap. Functional MRI during sleep in all subjects demonstrated increased blood flow in the same areas of the brain that were active while awake, when the subjects were learning the new material. This indicates that our brains continue to process new information while we sleep, and that sleep likely helps facilitate the memory encoding process.
We also know that sleep architecture, or the progression we make through various stages of sleep every night, changes significantly as we age. Our sleep becomes more fragmented, we are more easily awakened, and our slow wave sleep, sometimes referred to as “deep sleep,” progressively diminishes. Older adults generally sleep less than younger adults do and, interestingly, are better equipped to handle the effects of sleep deprivation. Perhaps because we are so used to it.
So what does this have to do with memory? If it’s been well established that short-term sleep deprivation can produce transient cognitive impairment, what about chronic sleep deprivation? Can this eventually lead to permanent memory loss? Does fragmented sleep lead to dementia, such as that of Alzheimer’s disease? There have been several recent studies that have attempted to better answer this important question.
In a multisite cohort of community-dwelling women aged 65 years or older (mean age of 82), researchers analyzed the effect of both sleep fragmentation from any cause and sleep fragmentation from sleep apnea on the risk of cognitive impairment, as measured approximately five years later with neuropsychological cognitive testing (2). They found that the presence of sleep apnea was associated with a 1.8-fold increased risk of developing cognitive impairment and dementia. This was after adjusting for several variables including age, race, weight, education, smoking, diabetes, and medication use.
Interestingly, this risk was not associated with sleep fragmentation from any cause. They found no significant association between cognitive impairment and sleep fragmentation measures such as the arousal index, wake after sleep onset (total time spent awake after initially falling asleep), or total sleep time. Furthermore, the risk of cognitive impairment seen in sleep apnea patients was very much correlated with the degree of oxygen desaturations throughout the night, indicating that it was not the increased arousal threshold but rather the low oxygen levels from the apneas themselves that contributed to the patients’ cognitive decline.
This same group of researchers presented new data recently at the 66th annual meeting of the American Academy of Neurology, in which they demonstrated, in a cohort of younger patients (age 37-52) that those who slept less than seven hours a night and reported more sleep fragmentation had a greater amount white matter changes on brain MRI (3). White matter changes, while nonspecific, can serve as an imaging marker of small vessel disease, a hardening of the small arteries in the brain, similar to what happens inside the small arteries of the heart in patients with coronary artery disease. In severe cases this can cause stroke, as well as dementia, and has been termed “vascular dementia” or “muli-infarct dementia” in the neurology literature.
In data also presented at the AAN meeting, another group of researchers demonstrated that sleep might serve to clear certain “toxic” protein products that have been linked to the development of Alzheimer disease.
Amyloid A-Beta peptide (AB) is protein cleavage product that can accumulate to form so-called “senile plaques.” These conglomerations of protein can then deposit in areas of the brain that are crucial to memory, language, and spatial awareness and can contribute to the some of the impairments we often see in patients with Alzheimer’s disease.
When mice were sleep deprived, they developed significantly more AB deposition. In addition, when the animals were allowed to eventually sleep, they cleared much of the AB from their brains. This lead the researchers to hypothesize that sleep deprivation or fragmentation could potentially lead to excessive AB release, thus leading to excessive amyloid deposition. In addition, stress and other environmental factors may also regulate AB levels.
So does sleep deprivation lead to permanent cognitive impairment or dementia, as that seen in Alzheimer’s disease? The results so far are mixed, and far from conclusive. One thing is for sure though — as we age, and our natural sleep architecture becomes increasingly fragmented, we should all be doing what we can to try and get a good night’s sleep. Most importantly, if any signs of sleep apnea are present — such as snoring, breath holding, gasping or choking, excessive sweating, restless sleep, or early morning headaches, to name but a few — your brain may be at risk, and you should ask your doctor about being evaluated by a sleep specialist.
Sources:
1. Walker MP, Stickgold R . Sleep, memory, and plasticity. Annu Rev Psychol. 2006; 57:139-66.0.
2. Yaffe, K et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011 Aug 10;306(6):613-9.
3. Yaffe, K et al. Poor Sleep and White Matter Quality among Middle Aged Adults. In: Proceedings of the 66th Annual Meeting of the American Academy of Neurology; 2014 Apr 25-May 3, Philadelphia (PA).
Mitchell Miglis, M.D., is a sleep neurologist in the Stanford Neurology Department and the Stanford Center for Sleep Sciences and Medicine. He specializes in the relationship between sleep medicine and autonomic disorders. The center is the birthplace of sleep medicine and includes research, clinical and educational programs that have advanced the field and improved patient care for decades. To learn more, visit our website.
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