International Business Department           Liu Bojia           August 23, 2023

When it comes to Alzheimer's disease (AD), the symptom that you may be familiar with is impaired memory function. As the disease progresses, people with AD do experience severe memory loss and have impaired cognitive function. But in addition to this, circadian rhythms are disrupted in about 80% of patients.

According to reports in the literature, AD patients are prone to abnormal sleep/wake cycles, especially difficulty falling asleep, insomnia, and cognitive disorganization at night. These sleep problems will undoubtedly further accelerate the progression of AD, i.e., creating a vicious cycle that is difficult to break.

  Professor Paula Desplats' team at the University of California, San Diego, has found that rhythm disorders do not only show up when the various symptoms of AD unfold, as believed in the past, but are present early on in the disease, and thus it is not a result of AD, but one of the drivers of AD.

  In the latest study in Cell Metabolism, the research team suggests a way to stop the harm of circadian rhythm disruption that is not only easy to use, but already has well-established strategies for its use. I'm sure many people trying to control their weight have heard of intermittent fasting, and you heard right, this method of severely restricting the time of eating can also help many people with AD to reduce the symptoms associated with abnormal rhythms and slow the progression of the disease.

  The idea behind this strategy is not difficult to understand: circadian rhythms regulate individual physiological processes through "clock" transcription molecules; in turn, rhythm-following behaviors can stimulate metabolic synchronization. Intermittent fasting is one such type of behavior that has a fixed clock. Some studies have found that intermittent fasting can even provide metabolic benefits in the presence of rhythmic disruption.

  Prof. Desplats has tested the effects of the 6:18 fasting method (6 hours of food and 18 hours of fasting) on mice modeling Huntington's disease, and found that intermittent fasting improved sleep cycles, enhanced exercise performance, and lowered inflammation levels in mice. Could this approach be equally effective in AD?

  With this question in mind, Prof. Desplats re-conducted the experiment using the same strategy as the 6 : 18 fasting method, but with a different test subject, the AD model mice.

  With no interference at all with feeding, the mice developed some fragmented sleep behavior during the day at around 6 months of age, and the sleep problems got worse as they got older. By 11 months of age, the mice had significantly reduced their total sleep time and experienced insomnia.

  In contrast, the AD mice, which were on an intermittent fast, showed a significant reduction in symptoms, especially in their sleep cycles, which became more stable. They were not hyperactive at night and rarely awoke suddenly when asleep.

  As mentioned at the beginning, the strict implementation of intermittent fasting can also in turn cause changes at the molecular level. The authors observed that many disease genes associated with AD, as well as genes associated with neuroinflammation, were downregulated by fasting. In addition, long-term adherence to intermittent fasting reduced the accumulation of beta-amyloid in the brains of mice, both in terms of quantity and occupied volume. In terms of time, amyloid plaque reduction was observed after performing intermittent fasting for seven weeks.

  The researchers noted that these results could quickly move to the clinic for validation, as its not dependent on drugs to achieve, and would be simpler and safer. "Intermittent fasting is a strategy that can be immediately integrated into life and if the results can be replicated in humans, it could quickly help people with AD." Prof. Desplats said.