Sleep, mice & Alzheimer’s

“Sleep helps the brain wash out toxins”.

This theory has been dominant in neuroscience while we are still trying to find an explanation for the sleep phenomenon. The glymphatic system was claimed to be a ‘macroscopic waste clearance system’ that functions to eliminate of soluble proteins and metabolites from the central nervous system. It’s also been described in a famous book by Matthew Walker ‘Why We Sleep’ (a very much recommended reading).

A fresh study (Nature Neuroscience) led by the?UK Dementia Research Institute (UK DRI) at Imperial College London however, suggests that this theory might not be true. The?researchers used a fluorescent dye to study the brains of mice (male mice). This allowed them to see how quickly the dye moved from fluid-filled cavities, called the ventricles, to other brain regions and enabled them to measure the rate of clearance of the dye from the brain directly.

The study found that the clearance and movement of fluid in the brains of mice was, in fact, markedly reduced during sleep (by 30%) and anaesthesia (by 50%).

This news may provide some relief to insomnia sufferers worried that their brain doesn’t get enough time for ‘waste cleaning’.

The findings have relevance for dementia research due to the increasing evidence of a link between poor sleep and Alzheimer’s (AD) risk. It has not been clear whether lack of sleep might cause AD, or whether it is simply an early symptom.?

Some evidence shows that sleep disturbance contributes to cognitive decline and may increase the risk of AD since disrupted sleep is associated with faster accumulation of beta-amyloid protein in the brain.

What else do we know about the connection between sleep and Alzheimer’s?

Other related studies

• 2024 study from Harvard University in Cambridge (Journal of the Neurological Sciences) used PET scans to link abnormal nighttime behaviors were linked with greater baseline of tau protein.?
• 2024 study at the Johns Hopkins Bloomberg School of Public Health (SLEEP) demonstrated that monitoring daily activity patterns using a wrist-worn device (actigraphs) may detect early warning signs of Alzheimer’s disease. Significant differences were found between this “amyloid-positive” group and “amyloid-negative” participants in mean activity in certain afternoon periods and differences in variability of activity across days in a broader range of time windows.
• 2024 study (Sleep Advances) that involved 243 older adults concluded that midpoint of sleep should be factored in when using sleep as a noninvasive biomarker for AD risk. Although midpoint of sleep is a measure of sleep behavior rather the function of circadian rhythm, individuals with both early and late sleep midpoint are at of AD. Later midpoint of sleep was associated with longer REM onset latency, decreased REM sleep time, and increased non-REM slow-wave activity.
• 2023 research from University of California, Berkeley (BMC Medicine) suggests that deep sleep might help alleviate AD symptoms. Superior amounts of deep, slow-wave sleep can significantly moderate the effect of beta-amyloid status on memory function.
• 2023 trial from Washington University School of Medicine in St. Louis (Annals of Neurology) showed that a sleeping pill, suvorexant, was able to acutely decrease both amyloid and tau levels - however, the trial was small (38 people) and short (2 nights). By a day after administration, both protein levels increased back to the original values. A bigger clinical trial on the sibject is currently in progress.
• 2023 meta-analysis (PLOS ONE) suggests that light therapy might help improve sleep and psycho-behavioral symptoms in people with AD. Light therapy improves sleep efficiency and reduces depressive symptoms and has no side effects. The meta-analysis included 15 high-quality studies from 2005-2022, total of 598 participants from 7 countries.
• 2023 study from the University of Pittsburgh and the University of Illinois suggests that menopausal women who experience frequent hot flashes during sleep may be at elevated risk of developing AD. Another study found that the first signs of the brain disorder can appear at about the same time women start menopause, suggesting the hormonal event might have implications for disease risk.

Two thirds of AD patients are women and more research is needed on the topic. 70% of women experience neurological symptoms during the menopausal transition and more research is needed in the area.

Read here about menopause and neuroscience.