Poor Sleep Quality in Older People Linked to Early Signs of Alzheimer’s

Poor Sleep Quality in Older People Linked to Early Signs of Alzheimer’s

People 60 or older with a disrupted pattern of deep sleep — the one that helps memory formation — have a higher accumulation of the Alzheimer’s hallmark tau protein in their brains, a study reports.

These findings highlight how poor-quality sleep later in life is a potential sign of brain health decline and supports the usefulness of noninvasive sleep analysis in the early detection of people at risk of developing Alzheimer’s disease.

“What’s interesting is that we saw this inverse relationship between decreased slow-wave sleep and more tau protein in people who were either cognitively normal or very mildly impaired, meaning that reduced slow-wave activity may be a marker for the transition between normal and impaired,” Brendan Lucey, MD, an assistant professor of neurology and director of the Washington University Sleep Medicine Center and the study’s first author, said in a press release.

“Measuring how people sleep may be a noninvasive way to screen for Alzheimer’s disease before or just as people begin to develop problems with memory and thinking,” Lucey said.

The study, “Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease,” was published in the journal Science Translational Medicine.

Accumulation of amyloid-beta plaques and tau protein aggregates in the brains of Alzheimer’s patients gets started long before (15 to 20 years) patients show any clinical signs of the disease. These protein aggregates precede the loss of nerve cells, shrinkage of the brain, and cognitive impairment.

This early period in which the brain is undergoing changes that will lead to the onset of Alzheimer’s symptoms represents a key window for early therapeutic intervention to slow neurodegeneration and disease progression.

Being able to detect this early phase of the disease, which researchers call “preclinical” Alzheimer’s because the disease mechanisms are in place but patients lack cognitive symptoms, is vital. But reliable markers are necessary.

Poor sleep quality and short sleep duration have been associated with an increased risk of cognitive impairment and Alzheimer’s by promoting amyloid-beta deposition in the brain.

Non-rapid eye movement (NREM) sleep is divided into three stages that reflect the transition from “light” to “deep” sleep. Stage 3, the deep stage, is also called slow-wave sleep (SWS) as it is characterized by low-frequency slow-wave activity (SWA).

Studies with animal models and humans have suggested a link between decreased NREM sleep slow wave activity and amyloid-beta deposition.

Researchers at Washington University School of Medicine monitored the sleep patterns of 119 people older than 60 over six nights at their homes. The majority (80%) were cognitively normal, and the rest very mildly impaired. All were enrolled in longitudinal studies of aging at the Knight Alzheimer’s Disease Research Center at Washington University.

Brain waves were captured during sleep by a portable electroencephalogram (EEG) monitor worn on the forehead, and body movements tracked with a wristwatch-like sensor. Participants also kept sleep logs, where they reported their sleeping time and daytime napping.

Participants’ cognitive performance was evaluated using the Clinical Dementia Rating (CDR) scale, a five-point scale used to characterize six domains of cognitive and functional performance.

Several markers associated with Alzheimer’s disease were also evaluated, namely amyloid-beta and tau protein aggregates measured by PET imaging (38 participants) or through lumbar puncture in the cerebrospinal fluid (CSF, 104 patients). CSF is the liquid surrounding the brain and spinal cord. Twenty-seven patients underwent both PET imaging and CSF analysis.

After adjusting the results for patients’ age and sex, researchers saw that decreased non-rapid eye movement slow wave activity, particularly at the frequency of 1-2 hertz, correlated with increased amyloid-beta deposition and higher levels of tau.

The ratio between tau protein and a specific form of amyloid-beta, called amyloid-beta 42, has been previously reported as a marker of early stages of Alzheimer’s, able to predict cognitive decline years in advance. A higher ratio of tau/amyloid-beta 42 also has been associated with poor sleep.

In agreement with these findings, researchers saw that decreased non-rapid eye movement slow wave activity was associated with increased tau/amyloid-beta 42 ratios in the CSF.

“The key is that it wasn’t the total amount of sleep that was linked to tau, it was the slow-wave sleep, which reflects quality of sleep,” Lucey said. “The people with increased tau pathology were actually sleeping more at night and napping more in the day, but they weren’t getting as good quality sleep.”

These results “suggest that the quality of sleep decreases with increasing tau despite increased sleep time,” researchers said, adding that “self-reported napping time per day may be an important question to screen individuals for tauopathy.”

Overall, these results suggest that changes in NREM sleep are a potential early sign of brain changes linked to Alzheimer’s, supporting the use of noninvasive sleep analysis to identify patients at risk of developing the disease.

“Because the study participants were predominantly cognitively normal with the remaining showing only very mild impairment, this suggests that decreased NREM SWA, especially at the lowest 1- to 2-hertz frequencies, might be associated with tau pathology either before or at the earliest stages of cognitive decline,” researchers stated.

“I don’t expect sleep monitoring to replace brain scans or cerebrospinal fluid analysis for identifying early signs of Alzheimer’s disease, but it could supplement them,” Lucey said. “It’s something that could be easily followed over time, and if someone’s sleep habits start changing, that could be a sign for doctors to take a closer look at what might be going on in their brains.”

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