Sleep disorders in Alzheimer’s disease: chicken or egg?

The sleeping brain

Picture of EEG recording
Attribution: By Petter Kallioinen (Own work), via Wikimedia Commons

Sleep has a vital restorative function, important for optimal day-time functioning. The brain’s activity during sleep can be detected with a device called electroencephalogram (EEG), which measures and records the electrical activity in the brain. EEG studies have found certain patterns in brain activity during sleep. These patterns have been grouped into two main types, rapid-eye-movement (REM, the dream-phase) and non-rapid-eye-movement (NREM) sleep. The NREM sleep is further divided into three sleep stages, characterized by progressively slower brain waves and deeper sleep. Typically the normal adult enters sleep through NREM sleep and progresses through stages one, two and three, before moving on to REM sleep after about 80 minutes. This pattern is repeated several times during the night and each cycle, composed of REM and NREM sleep, lasts for about 90 minutes in adults. As the night progresses there is a proportionate reduction in slow wave sleep and increase in REM sleep within each cycle.

Age-related changes in sleep patterns
Old Man RestingThe notion that older people need fewer hours of sleep is a myth. Our need for sleep remains constant throughout adulthood, i.e. between seven and nine hours of sleep each night. However, the difficulties obtaining a decent night’s sleep in one block get more pronounced with increasing age. As people get older, changes in sleep patterns are common, as senior citizens tend to have more trouble falling asleep and staying asleep. EEG studies have moreover shown that as we age, the proportion of the deeper, slow wave sleep diminishes and more time is spent in the lighter stages of sleep.

A brand new study by Bryce Mander and colleagues showed that loss of brain volume, declining memory and poor sleep, all associated with normal aging, appear to be intertwined. Their findings suggest that age-related brain volume loss (in the medial prefrontal cortex) undermines sleep quality by reducing slow-wave sleep in older adults, negatively affecting long-term memory. In other words, structural brain changes mediate sleep disruption in the elderly, resulting in dwindling ability to remember.

Sleep disorders and Alzheimer’s disease
One of the hallmarks of Alzheimer’s disease is the damaging accumulation of amyloid-beta protein in the brain. The sleep-wake cycle may play a role in the development of Alzheimer’s disease, as some studies have shown that sleep deprivation in mice can increase amyloid-beta deposits in the brain. One study showed however, that the sleep-wake cycle of mice was disrupted following the formation of amyloid-beta. When the amyloid was eliminated from the brain, the sleep-wake cycle returned to normal, suggesting that the sleep disturbances were caused by the amyloid-beta formation.

Research using human subjects has also found ties between sleep disorders and Alzheimer’s disease. In sleep apnea (or sleep-disordered breathing) the airways leading from the nose and mouth to the lungs collapse, interfering with breathing so the brain and other organs are deprived of oxygen. Kristine Yaffe and her colleagues studied the association between sleep apnea and dementia. Their results showed that elderly women suffering from sleep apnea had almost twice the risk of developing dementia in the next five years, compared to their peers without the disorder.

Another study showed that sleep disturbances seem to contribute to, or reflect, the early stages of Alzheimer’s disease, independently of cognitive decline. Increased sleep and/or sleepiness during the daytime seemed to be a particularly strong predictor of subsequent Alzheimer’s diagnosis. The authors concluded that changes in sleep-wake patterns could be indicative of the first, or preclinical, stage of Alzheimer’s disease.

Sleep disruptions: chicken or egg?
Our brain progressively looses some of its volume as we age and some have suggested that the changes in sleep architecture are byproduct of this volume-loss. But could it be the other way around? Is it possible that the loss of brain volume is a direct or indirect result of sleep disturbances? In the case of Alzheimer’s disease, are sleep disturbances an early sign of a developing disease or do these disturbances contribute to the disease’s progression?

Well, this is not clear yet and the results from the studies cited above show that the connection is certainly not a one-way causal relationship. Moreover, some research have shown that cognitive impairment and cortical thinning associated with sleep apnea seem to be reversible with treatment.

More on the science of sleep from Harvard:

Here is a video posted by futurityvideo on YouTube, on the effect of sleep disturbances on amyloid build-up.

Built on:

-Canessa, N., Castronovo, V., Cappa, S. F., Aloia, M. S., Marelli, S., Falini, A. o.fl. (2010). Obstructive Sleep Apnea: Brain Structural Changes and Neurocognitive Function before and after Treatment. American Journal of Respiratory and Critical Care Medicine, 183(10), 1419-1426.

-Edwards, B. A., O’Driscoll, D. M., Ali, A., Jordan, A. S., Trinder, J. og Malhotra, A. (2010). Aging and Sleep: Physiology and Pathophysiology. Respiratory and critical care medicine, 31(5), 618-633.

-Hannesdottir, K., Snaedal, J., Josefsson, A., Arvidsson, A. og Gislason, T. (2011). Evidence of Sleep Apnea in MCI/Mild Dementia. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 7(4), S172.

-Mander, B. A., Rao, V., Lu, B., Saletin, J. M., Lindquist, J. R., Ancoli-Israel, S. o.fl. (2012). Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci, advance online publication.

-Roh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J. o.fl. (2012). Disruption of the sleep-wake cycle and diurnal fluctuation of beta-amyloid in mice with Alzheimer’s disease pathology. Science Translational Medicine, 4(150), 150ra122.

-Yaffe, K., Laffan, A. M., Harrison, S. L., Redline, S., Spira, A. P., Ensrud, K. E. o.fl. (2011). Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA, 306(6), 613-619.

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