Scientists suggest intermittent fasting could “dramatically improve the lives of people with Alzheimer’s”

23 Aug 2023 --- US-based researchers suggest that time-restricted feeding may correct circadian disruptions associated with Alzheimer’s disease in a mouse model, improving memory, sleep and cognitive function. The study’s results indicate intermittent fasting could alter the trajectory of Alzheimer’s disease.

Feeding mice during a window of six hours per day for three months, without calorie restrictions, reduced the accumulation of amyloid proteins in the brain. Alzheimer’s is characterized by the buildup of these proteins, which form sticky plaques on the brain and can cause cells to die.

The researchers note that almost all Alzheimer’s disease patients experience disruptions to their circadian rhythm – the internal biological clock that regulates many physiological processes – leading to difficulty sleeping and worsening cognitive function at night.

“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,” says senior study author Paula Desplats, Ph.D., professor in the department of neurosciences at the UC San Diego School of Medicine.

“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 study on mice suggests circadian disruption may drive Alzheimer’s pathology.Boosting the circadian clock
For humans, the time-restricted schedule used in the study, published in Cell Metabolism, would translate to approximately 14 hours of fasting daily.

The researchers used transgenic mice that express mutations associated with early-onset Alzheimer’s disease. The control group had access to food 24 hours a day, while time-restricted-fed mice could only eat within six hours each day.

Mice on the time-restricted schedule had better memory, were less hyperactive at night, followed a more regular sleep schedule and experienced fewer sleep disruptions than control mice. They also performed better on cognitive assessments, which the researchers note demonstrates that time-restricted feeding helped mitigate the behavioral symptoms of Alzheimer’s disease.

“Circadian disruptions in Alzheimer’s are the leading cause of nursing home placement,” says Desplats. “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.”

The researchers explain that the study shows that time-restricted feeding changed crucial pathways that trigger neurodegeneration. They found that the treatment normalized the expression of specific genes associated with Alzheimer’s disease and neuroinflammation.

To determine clinical relevance, the authors note follow-up research should determine if the interventions are also effective if initiated after the onset of amyloid plaque, which is when Alzheimer’s clinical diagnoses are made.

The scientists note that future studies are needed to investigate the mechanisms behind the study’s outcomes and explore the therapeutic potential of time-restricted eating.

Human clinical trials
The effect of fasting on different aspects of health and disease continues to be an area of research interest, says Dr. Susan Kohlhaas, executive director of research and partnerships at Alzheimer’s Research UK. She welcomes the study’s outcomes but points to limitations new research should overcome.

“As the research was carried out in mice, we do not know if the beneficial effects of a restricted diet will be the same in humans, how long any benefits would last or how long the time window for restricted eating would need to be to show benefit. This is further complicated by the difficulty in conducting clinical trials in people as restricted eating can be difficult to study in the context of large-scale and conclusive clinical trials.”

Clinical trials are needed to determine if the results can be repeated in humans.Kohlhaas adds that studies in animal models are the first step in understanding how different biological processes work in the brain. Still, these must be investigated in clinical trials to determine whether the approach would be helpful in people living with Alzheimer’s disease.

“We’re at an exciting time in Alzheimer’s research, with the first generation of treatments coming through late-stage trials,” she highlights.

“Our next step must be to invest in new areas of research that help us develop and test treatment strategies that can slow, stop or reverse Alzheimer’s disease. It’s studies like this that add to our fundamental understanding of dementia, which give us important clues to how we might tackle the disease.”

Food for thought
The researchers are optimistic that their findings could be translated to clinics as they rely on lifestyle changes.

“Time-restricted feeding is a strategy that people can easily and immediately integrate into their lives,” says 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 health impacts of intermittent fasting have been the focus of several studies. For example, researchers found that restricting the eating window impacts 22 regions of the body and brain, which could have potential benefits for cancer, heart disease and hypertension.

A Chinese study suggested that intermittent fasting could help reverse Type 2 diabetes, although experts argued this effect could have been supported by weight loss associated with fasting.

By Jolanda van Hal

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