According to Nature Reviews Neurology,2013(9):657, sleep disorders have previously been shown to be associated with Alzheimer’s disease (AD) and age-related cognitive decline. Nowadays, three studies have elucidated the relationship between sleep and the pathological processes that constitute neurodegeneration and cognitive dysfunction. Adam Spira and colleagues found that poor sleep quality in older adults was associated with increased levels of the well-known biomarker of AD, β-amyloid peptide (Aβ), in the brain, and Andrew Lim and colleagues showed that good sleep reduced the incidence of AD and attenuated AD pathology in carriers of the apolipoprotein E4 allele (ApoEε4), which is responsible for the development of sporadic AD. allele is an important risk genetic factor for the development of sporadic AD. In conjunction with findings in humans, MaikenNedergaard and her team found in mice that sleep enhances the ability to clear Aβ peptides from the interstitial fluid of the brain. It has been shown that sleep deprivation in mouse models of AD increases the deposition of age spots. In humans, on the other hand, β-amyloid peptide (Aβ) levels in the cerebrospinal fluid are altered in response to sleep cycles. In their study, Spira et al. selected 70 community-dwelling older adults (mean age 76 years) from the Baltimore Longitudinal Study of Aging and combined data on the amount of beta-amyloid peptide (Aβ) deposition obtained by positron emission tomography (PET) with the subjects’ self-reported reports of sleep duration and quality. From these, they found that subjects with short and poor sleep duration had higher Aβ deposition than those with good sleep quality. The researchers noted that their study did not address the causal relationship between sleep quality and beta-amyloid peptide (Aβ) accumulation, and Spira said, “We need further studies to verify whether there is such a sequential relationship between poor sleep quality and increased beta-amyloid peptide (Aβ) deposition.” Again, subjects’ self-reported sleep quality needs to be validated by objective sleep quality assessment metrics. In examining whether the ApoEε4 allele is a risk factor for increased onset of AD, which may be influenced by sleep, Lim and his colleagues collected ApoE genotype data, cognitive performance test results, and follow-up data from 689 community-dwelling older adults (mean age 82 years) over a 6-year period. In addition, there were credible brain autopsy data from 201 AD patients with adequate amounts of beta-amyloid peptide (Aβ) and another characteristic AD marker, neurofibrillary tangles. Lim et al. found that good sleep reduced the risk of AD and attenuated the progression of age-related cognitive decline and neurofibrillary tangles in carriers of the ApoE4 allele (ApoEε4). The risk of developing AD may be particularly high in some people who have poor sleep quality,” Lim noted. Nedergaard and colleagues’ study in mice took an important step toward uncovering the neuropathological mechanisms linking sleep disorders to cognitive impairment . In wild-type mice and mouse models of AD, the level of beta-amyloid peptide (Aβ) in the interstitial fluid is associated with the length of time awake and the amount of reduction during sleep. nedergaard’s team has previously described the role of the brain drainage system, which removes proteins from the interstitial fluid through recirculation of the cerebrospinal fluid and can also be used to exchange the interstitial fluid. His team also made the hypothesis that the energy consumption of fluid and soluble molecules for transport may also be affected by the sleep cycle. Nedergaard’s team used fluorescent labeling and two-photon imaging techniques to closely observe interstitial fluid and β-amyloid peptide (Aβ) transport in awake, sleeping and anesthetized mice, respectively. To their surprise, they found that the interstitial gaps in sleeping and anesthetized mice accounted for 60% of the brain, larger than in awake mice, thus increasing the exchange of cerebrospinal and interstitial fluid and thus effectively clearing the brain of neurotoxins produced during sleep. In summary, these studies explain the mechanisms involved in sleep disorders and pathophysiological processes in AD and suggest the importance of sleep, which may be associated with an enhanced ability to clear metabolic waste from the brain. According to Nedergaard, their findings suggest the idea that neurologists should take patients with sleep disorders seriously and treat them aggressively. both Lim and Spira suggest that future research directions should include interventional trials. according to Spira, “if we find evidence in humans that poor sleep quality occurs before Aβ deposition, or that it increases Aβ deposition, then we should be able to find evidence that poor sleep quality occurs before Aβ deposition. or it increases the rate of Aβ deposition, we will need intervention trials to further investigate whether the onset of AD can be prevented or slowed by improving sleep quality and reducing insomnia.”