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Deep Sleep May Mitigate the Impact of Alzheimer’s Pathology

Deep sleep may function as a buffer against cognitive decline in older adults with Alzheimer’s disease (AD) pathology by protecting cognitive reserve, new research suggests.

Investigators found that deep sleep, also known as non-REM slow-wave sleep, can protect memory function in cognitively normal adults with a high beta-amyloid burden.

“Think of deep sleep almost like a life raft that keeps memory afloat, rather than memory getting dragged down by the weight of Alzheimer’s disease pathology,” senior investigator Matthew Walker, PhD, professor of neuroscience and psychology, University of California Berkeley, said in a news release.

The study was published online May 3 in BMC Medicine.

Resilience Factor

Studying resilience to existing brain pathology is “an exciting new research direction,” lead author Zsófia Zavecz, PhD, with the Center for Human Sleep Science at Cal Berkeley, told Medscape Medical News.

“That is, what factors explain the individual differences in cognitive function despite the same level of brain pathology, and how do some people with significant pathology have largely preserved memory?” she added.

The study included 62 cognitively normal older adults from the Berkeley Aging Cohort Study.

Sleep EEG recordings were obtained over two nights in a sleep lab and PET scans were used to quantify beta-amyloid. Half of the participants had high beta-amyloid burden and half were beta-amyloid-negative.

After the sleep studies, all participants completed a memory task involving matching names to faces.

The results suggest that deep NREM slow-wave sleep significantly moderates the effect of beta-amyloid status on memory function.

Specifically, NREM slow-wave activity selectively supported superior memory function in adults with high beta-amyloid burden, who are most in need of cognitive reserve (B = 2.694, P = .019), the researchers report.

In contrast, adults without significant beta-amyloid pathological burden — and thus without the same need for cognitive reserve — did not similarly benefit from NREM slow-wave activity (B = –0.115, P = .876).

The findings remained significant after adjusting for age, sex, BMI, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity.

Zavecz said there are several potential reasons why deep sleep may support cognitive reserve.

One is that during deep sleep specifically, memories are replayed in the brain, and this results in a “neural reorganization” that helps stabilize the memory and make it more permanent.

“Other explanations include deep sleep’s role in maintaining homeostasis in the brain’s capacity to form new neural connections and providing an optimal brain state for the clearance of toxins interfering with healthy brain functioning,” she noted.

“The extent to which sleep could offer a protective buffer against severe cognitive impairment remains to be tested. However, this study is the first step in hopefully a series of new research that will investigate sleep as a cognitive reserve factor,” said Zavecz.

Encouraging Data

Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said although study sample is small, the results are “encouraging because sleep is a modifiable factor and can therefore be targeted.”

“More work is needed in a larger population before we can fully leverage this stage of sleep to reduce the risk of developing cognitive decline,” Griffin told Medscape Medical News.

Also weighing in on this research for Medscape Medical News, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said, the study is “exciting on two fronts — we may have an additional marker for the development of Alzheimer’s disease to predict risk and track disease, but also targets for early intervention with sleep architecture–enhancing therapies, be they drug, device, or digital.”

“For the sake of our brain health, we all must get very familiar with the concept of cognitive or brain reserve,” said Lakhan, who was not involved in the study.

“Brain reserve refers to our ability to buttress against the threat of dementia and classically it’s been associated with ongoing brain stimulation (ie, higher education, cognitive demanding job),” he noted.

“This line of research now opens the door that optimal sleep health — especially deep NREM slow wave sleep — correlates with greater brain reserve against Alzheimer’s disease,” Lakhan said.

The study was supported by the National Institutes of Health and the University of California, Berkeley. Walker serves as an advisor to and has equity interest in Bryte, Shuni, Oura, and StimScience. Zavecz and Lakhan report no relevant financial relationships.

BMC Med. Published online May 3, 2023. Full text

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