Intermittent Calorie Restriction Enhances Cognitive Function and Memory in Older Adults, Pilot Study Shows

In an 8-week randomized clinical trial involving 40 overweight, cognitively healthy older adults with insulin resistance, researchers explored the impact of two different interventions on brain health. Participants were assigned to either a 5:2 intermittent fasting regimen—consisting of 2 days with a restricted intake of 480 calories per day (provided through meal replacement shakes) and five days of a healthy living diet based on portion control and calorie reduction guidelines—or a "healthy living" diet alone.

Both interventions improved executive function and memory, with intermittent fasting demonstrating superior results on specific cognitive measures, according to Dimitrios Kapogiannis, MD, from the National Institute on Aging (NIA) and Johns Hopkins University School of Medicine. The findings were presented in a poster at the Alzheimer’s Association International Conference.

A diet may enhance brain health in older adults with metabolic impairments. Considering this, Dr. Kapogiannis and colleagues aimed to assess whether intermittent calorie restriction can reduce insulin resistance, enhance cognitive performance, improve brain metabolism and function, and normalize biomarkers associated with Alzheimer's in adults aged 55 to 70.

The following were the key findings of the study:

• While intermittent fasting led to more significant weight loss, both diets produced similar improvements in insulin signaling biomarkers in neuron-derived extracellular vesicles.
• The researchers also showed comparable effects in reducing the brain-age-gap estimate (which reflects the rate of biological brain aging) on magnetic resonance imaging, lowering brain glucose levels on magnetic resonance spectroscopy, and enhancing blood biomarkers related to carbohydrate and lipid metabolism. Changes in cerebrospinal fluid biomarkers for Alzheimer’s disease were minimal.
• Intermittent fasting and healthy living improved executive function and memory, and intermittent fasting benefited more certain cognitive measures.
• In exploratory analyses, sex, body mass index, and apolipoprotein E and SLC16A7 genotypes modulated diet effects.

The study offers a framework for evaluating the impact of dietary interventions on brain health and encourages additional research into intermittent fasting and continuous diets for optimizing cognitive function, the researchers wrote.

The researchers noted that the trial's short duration might have missed effects that developed beyond the 8 weeks. The study was sufficiently powered to detect only large or moderate effects over time and between the two interventions. They also acknowledged that some improvements in cognitive performance might be attributable to practice effects.

Reference:

Kapogiannis, D., Manolopoulos, A., Mullins, R., Avgerinos, K., Delgado-Peraza, F., Mustapic, M., Nogueras-Ortiz, C., Yao, P. J., Pucha, K. A., Brooks, J., Chen, Q., Haas, S. S., Ge, R., Hartnell, L. M., Cookson, M. R., Egan, J. M., Frangou, S., & Mattson, M. P. (2024). Brain responses to intermittent fasting and the healthy living diet in older adults. Cell Metabolism. https://doi.org/10.1016/j.cmet.2024.05.017