Six million Americans are currently living with Alzheimer’s disease, with numbers expected to jump to around 13 million by 2050. This doesn’t take into account the many more millions of loved ones whose lives are also upended by the progressive neurodegenerative disease.
Around 80% of Alzheimer’s sufferers also experience severe disruptions to their circadian rhythms, the internal biological clock that regulates many crucial physiological processes. This often presents as increased confusion at night, also known as sundowning, sleeping difficulties, and a change in the sleep/wake cycle. And there are currently no treatments targeting this aspect of the disease.
“Circadian disruptions in Alzheimer’s are the leading cause of nursing home placement,” said senior author Paula Desplats, professor in the Department of Neurosciences at the University of California (UC) San Diego School of Medicine. “Anything we can do to help patients restore their circadian rhythm will make a huge difference in how we manage Alzheimer’s in the clinic and how caregivers help patients manage the disease at home.”
In a study on mice with Alzheimer's, the UC San Diego researchers discovered that feeding them intermittently, with a focus on circadian rhythms, corrected the disruption to their internal biological clocks and alleviated those debilitating symptoms.
The mice, fed on a precise time-restricted schedule while still eating the same amount of food in the day, showed big improvements in cognitive function (especially memory) and had a reduction in brain amyloid protein buildup.
“For many years, we assumed that the circadian disruptions seen in people with Alzheimer’s are a result of neurodegeneration, but we’re now learning it may be the other way around – circadian disruption may be one of the main drivers of Alzheimer’s pathology,” said Desplats. “This makes circadian disruptions a promising target for new Alzheimer’s treatments, and our findings provide the proof-of-concept for an easy and accessible way to correct these disruptions.”
The mice were given their food in a six-hour window each day; for humans, the researchers say this would translate to around 14 hours of daily fasting time.
When tested against a control group that was provided food around the clock, the fasted cohort performed better in memory tests, were less hyperactive at night, followed a more regular sleep schedule, and had fewer disruptions. As well as memory, the fasted mice performed better on other cognitive tests, suggesting that the time-restricted eating regimen countered many Alzheimer’s disease symptoms.
It’s not the first study that’s looked at the connection between intermittent fasting and brain health. Again in mice, scientists noted a boost in long-term memory when animals were put on a fasting schedule, and how on a molecular level it may assist the body's natural protein-disposal mechanisms in clearing out the debris that’s been linked to Alzheimer’s.
This latest study also reveals that intermittent fasting guided by the biological clock has a distinct impact on neurological mechanisms. Multiple genes linked to Alzheimer’s and neuroinflammation expressed differently in the fasted mice, which calls for further investigation, and there was a reduction in the accumulated amyloid proteins in the brain.
While, again, the research was conducted on a mouse model, it’s a promising route of inquiry that, if proven to be just as beneficial in humans, could be easily integrated into clinical treatment. It also only requires lifestyle changes, rather than drugs.
The authors believe the findings will pave the way for a human clinical trial.
“Time-restricted feeding is a strategy that people can easily and immediately integrate into their lives,” said Desplats. “If we can reproduce our results in humans, this approach could be a simple way to dramatically improve the lives of people living with Alzheimer’s and those who care for them.”
The study was published in the journal Cell Metabolism.
