— Pilot Study Paves the Way for Larger Trials on Brain Health Assessment

PHILADELPHIA -- In a preliminary investigation, intermittent calorie restriction improved executive function and memory in older adults without cognitive impairments.

This 8-week randomized study involved 40 overweight, cognitively healthy seniors with insulin resistance. Researchers compared two dietary strategies: a 5:2 intermittent fasting approach versus a “healthy living” diet, which followed USDA guidelines on portion control and calorie moderation. Participants following the 5:2 plan consumed 480 calories per day (via two meal replacement shakes) for two days, while adhering to the healthy living regimen on the other five days.

Both strategies led to enhancements in executive function and memory, though the intermittent fasting group demonstrated slightly superior improvement in certain cognitive tests, according to lead researcher Dimitrios Kapogiannis, MD, of the National Institute on Aging (NIA) and Johns Hopkins University School of Medicine. The findings were showcased in a poster presented at the Alzheimer’s Association International Conference.

The results were also published in the journal Cell Metabolism.

The goal of this exploratory study was to investigate whether intermittent calorie restriction could reduce insulin resistance, enhance brain performance, improve brain function and metabolism, and normalize Alzheimer's-related biomarkers in individuals aged 55 to 70.

"There's a common belief that adopting a nutritious diet or practicing intermittent fasting can help delay cognitive decline as we age. Our study adds evidence to that belief," Kapogiannis told MedPage Today.

“This pilot study lays the foundation for larger clinical trials exploring various dietary strategies to promote brain health and support healthier, longer lives,” he added.

Previous research has suggested a link between insulin metabolism and the risk of Alzheimer’s. Experiments in animals have shown that insulin plays a role in memory function and that intermittent fasting might offer benefits for neurodegenerative conditions.

Kapogiannis noted that excess weight contributes to peripheral insulin resistance and may accelerate brain aging. In this study, both dietary interventions reduced BMI and waist circumference, although intermittent fasting was more effective. The fasting group showed indications of elevated ketogenesis alongside strong diet adherence, unlike the healthy living diet group.

After eight weeks, both groups had similar effects on improving biomarkers connected to insulin signaling in neuron-derived extracellular vesicles. Brain glucose levels, measured using magnetic resonance spectroscopy, declined under both diets, with intermittent fasting having a slightly stronger impact. Additionally, BrainAGE, an MRI indicator of brain aging rate, decreased in both groups.

In terms of cognitive outcomes, composite scores for executive function significantly improved in the intermittent fasting group but not in the healthy living group. Additionally, learning and memory, particularly as assessed via the California Verbal Learning Test's long-delay cued recall task, saw notable improvement with intermittent fasting, while the healthy living diet did not produce such improvements. Logical memory enhanced in both groups.

Physical activity patterns, tracked with actigraphy, showed that sedentary periods decreased among those on the intermittent fasting diet but increased in the healthy living group.

Despite a reduction in brain aging measures, levels of amyloid-beta 42 and phosphorylated-tau (p-tau) 181—biomarkers associated with Alzheimer’s—remained unchanged in the cerebrospinal fluid during the 8-week study. Additionally, neurofilament light chain (NfL) levels increased in both dietary groups.

Kapogiannis and his team recruited 40 older adults with a body mass index (BMI) of 27.5 or higher between 2015 and 2022 from the NIA Clinical Research Unit. Twenty people participated in the intermittent fasting group, and 20 followed the healthy living diet, with a mean age of 63.2. Of the participants, 60% were female, 62.5% were Caucasian, and the average BMI was 34.4.

The short study duration limited the detection of effects beyond the 8-week timeframe, the researchers noted. The study was adequately powered to observe only large or moderate effects across time and between dietary interventions. Improvements in cognitive performance might also partially stem from participants gaining familiarity with the tests over time, the team acknowledged.

Disclosures

This study was funded by the NIA.

Kapogiannis declared no competing interests.

Primary Source

Alzheimer's Association International Conference

Source Reference: Kapogiannis D, et al. "Brain effects of 5:2 intermittent fasting and the healthy living diet in a randomized clinical trial" AAIC 2024; Poster Sunday-776.