This study suggests that a longer time to enter REM sleep may be an early indicator of brain changes associated with Alzheimer’s disease. Because these brain changes can occur many years before the first clinical symptoms appear, measuring REM latency may be useful in identifying individuals at risk of developing the disease in the future.
This study investigated how sleep structure, in particular REM sleep (the phase of sleep associated with vivid dreaming and memory processing), may be linked to the development of Alzheimer’s disease (AD) and other related dementias.
Sleep disturbances are common in patients with dementia and have been linked to brain changes characteristic of the disease, such as the accumulation of amyloid beta (Aβ) and tau proteins. Even in people without symptoms of dementia, altered sleep patterns may be linked to an increased risk of developing the disease in the future.
Previous research has suggested that sleep problems may influence the progression of Alzheimer’s disease. Studies of sleep deprivation have shown that it can lead to an increase in tau protein in the brain, both in animal experiments and in humans.
Other studies have found that people who sleep poorly or have fragmented sleep may have higher levels of beta-amyloid, a substance that builds up in the brains of Alzheimer's patients. In addition, certain stages of sleep have been shown to play an important role in this process.
Slow-wave sleep (SWS), which occurs in the deepest stages of non-rapid eye movement (NREM) sleep, plays a critical role in clearing metabolic waste products from the brain, including beta-amyloid.
When this phase of sleep is disrupted, there may be an increase in the deposition of these proteins over time. In addition, one study found that decreasing slow-wave sleep with advancing age may increase the risk of developing dementia.
Although REM sleep is widely recognized as critical for memory consolidation, its impact on the pathophysiology of Alzheimer’s disease remains poorly understood.
However, there is emerging evidence that this phase of sleep may be linked to early neurodegenerative changes.
Sleep stages with polysomnographic recordings
People with a genetic predisposition to Alzheimer's, such as carriers of the APOE ε4 variant, tend to have less REM sleep, even before they show symptoms of dementia.
In addition, studies suggest that less time in REM sleep is associated with greater deposition of beta-amyloid and smaller brain volume in regions vulnerable to neurodegeneration.
Despite these findings, it is still unclear which characteristics of sleep are most relevant to the pathological processes of Alzheimer's disease and other dementias. Therefore, this study sought to better understand the relationship between REM sleep and biomarkers of the disease.
To do this, the researchers analyzed data from 128 middle-aged to older adults, including people diagnosed with Alzheimer's, individuals with mild cognitive impairment (an intermediate stage between normal aging and dementia), and people with normal cognition.
Participants underwent polysomnography (PSG) scans to record their sleep quality, including how long it took them to enter REM sleep (REM latency).
Polysomnography (PSG)
In addition, PET scans were performed to measure the amount of beta-amyloid in the brain, and blood tests were performed to detect biomarkers such as phosphorylated tau (p-tau181), neurofilament light (NfL), and brain-derived neurotrophic factor (BDNF), a protein essential for the survival of neurons.
The researchers observed that participants who took longer to enter REM sleep had greater accumulation of beta-amyloid in the brain, as well as higher levels of p-tau181 in the blood, a marker of neurodegeneration.
They also observed that these people had reduced levels of BDNF, which may indicate a weakening of neural connections and a greater vulnerability to Alzheimer's.
These associations remained significant even after the researchers adjusted for other factors that could influence the data, such as age, gender, genetic background (APOE ε4 status), and cognitive level of the participants.
In addition, the relationship between prolonged REM latency and biomarkers of the disease was observed in all groups of participants, regardless of whether they already had symptoms of Alzheimer's or not.
This study suggests that a longer time to enter REM sleep may be an early indicator of brain changes associated with Alzheimer's disease.
Medications that regulate the orexinergic system, responsible for controlling sleep and wakefulness, could be explored as potential interventions to improve the quality of REM sleep and reduce the risk of Alzheimer's.
In summary, this study reinforces the importance of sleep in brain health and suggests that altered REM sleep may be a risk factor for neurodegeneration.
READ MORE:
Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease
Jiangli Jin, Jiong Chen, Clémence Cavaillès, Kristine Yaffe, Joseph Winer, Laura Stankeviciute, Brendan P. Lucey, Xiao Zhou, Song Gao, Dantao Peng, Yue Leng
Alzheimer’s & Dementia. First published: 27 January 2025
Abstract:
Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear. We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), and plasma biomarker analysis: phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and brain-derived neurotrophic factor (BDNF). After adjusting for demographics, apolipoprotein E (APOE) ε4 status, cognition, and comorbidities, the highest tertile of REM latency was associated with higher Aβ burden (β = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.002), elevated p-tau181 (β = 0.19, 95% CI: 0.02 to 0.13, p = 0.002), and reduced BDNF levels (β = -0.47, 95% CI: –0.68 to –0.13, p = 0.013), compared to the lowest tertile. Prolonged REM latency may serve as a novel marker or risk factor for AD/ADRD pathogenesis.
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