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PHILADELPHIA -- Intermittent calorie restriction improved executive function and memory measures in cognitively intact older adults, an exploratory pilot study suggested.

The 8-week randomized of 40 overweight, cognitively normal older adults with insulin resistance examined the effect of two interventions -- a 5:2 intermittent fasting plan versus a "healthy living" diet based on portion control and calorie reduction from the U.S. Department of Agriculture -- on brain health. The 5:2 intermittent fasting group had 2 days of food intake of 480 calories/day (two meal replacement shakes), and 5 days of a healthy living diet.

Both interventions improved executive function and memory, with intermittent fasting showing better results on certain cognitive measures, said Dimitrios Kapogiannis, MD, of the National Institute on Aging (NIA) and the Johns Hopkins University School of Medicine in Baltimore, in a poster presented at the Alzheimer's Association International Conference.

The findings also were published in .

The study aimed to determine whether intermittent calorie restriction could lower insulin resistance, improve cognitive performance, brain metabolism and function, and normalize Alzheimer's-associated biomarkers in adults ages 55 to 70.

"Many people think that eating a healthy diet or following an intermittent fasting regimen are good ways to stave off cognitive decline during aging, but our study actually provided supporting evidence," Kapogiannis told MedPage Today.

"Our study lays the groundwork for larger clinical trials that will examine a variety of dietary interventions that will help people have good brain health and live healthier, longer lives," he said.

Previous studies have tied insulin metabolism with . Animal studies have suggested that insulin contributes to normal and intermittent fasting in neurodegenerative diseases.

Excessive weight is implicated in peripheral insulin resistance and faster brain aging, Kapogiannis noted. In this study, both diets decreased BMI and waist conference, but results were better with intermittent fasting. The intermittent fasting group had markers suggesting increased ketogenesis and high compliance; the healthy living diet group did not.

At 8 weeks, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles. Brain glucose on magnetic resonance spectroscopy was reduced with both diets, more so with intermittent fasting, the researchers noted. BrainAGE, an MRI measure of the , decreased with both diets.

Within the groups, executive function composite scores improved significantly with the intermittent fasting diet, but not with the healthy living diet. Learning and memory assessed with the long-delay cued recall task on the also improved significantly with the intermittent fasting diet, while the healthy living diet showed no effect. Logical memory improved across both groups.

Actigraphy data showed that sedentary bouts decreased with intermittent fasting and increased with the healthy living diet.

Despite the decrease in brain aging measures, levels of amyloid-beta 42 and phosphorylated-tau (p-tau) 181 did not change in cerebrospinal fluid with either diet during the 8-week timeframe. Neurofilament light chain (NfL) increased in both groups.

Kapogiannis and co-authors enrolled 40 older adults with a BMI of 27.5 or higher from 2015 to 2022 at the NIA Clinical Research Unit. Twenty people in the intermittent fasting group and 20 in the healthy living diet group completed the study. Mean age of all participants was 63.2; 60% were women, 62.5% were Caucasian, and mean BMI was 34.4.

The trial duration was short and effects that may have occurred beyond week 8 may have been missed, the researchers said. The study had sufficient power to detect only large or moderate effects over time and between the two interventions. Cognitive performance improvements may partly reflect practice effects, they acknowledged.

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