Two Diets Linked to Improved Cognitive Function and Slowed Brain Aging

An intermittent fasting (IF) diet and a standard healthy living (HL) diet focused on healthy foods lead to weight loss, reduced insulin resistance (IR), and slowed brain aging in overweight older adults with IR, a new study finds. However, neither diet has an effect on biomarkers of Alzheimer’s disease (AD).

Although researchers found that both diets had benefits, some results were more robust for the IF diet.

“The study provides guidance for assessing the effects of dietary interventions on the brain and motivates further research into intermittent fasting and continuous diets to optimize brain health,” wrote the researchers, led by Dr. Dimitrios Kapogiannis, chief of the section of human neurobiology at the National Institute on Aging and assistant professor of neurology at the Johns Hopkins University School of Medicine.

The results were published online on June 19 in Cell metabolism.

Cognitive results

The incidence of IR — the decreased sensitivity of cells to insulin that is a hallmark of type 2 diabetes — increases with age and obesity, increasing the risk of accelerated brain aging as well as Alzheimer’s disease and related dementias (ADRD) in older, overweight people.

Research has shown that a healthy diet benefits overall health, but it is unclear whether and to what extent it improves brain health beyond improving overall health.

The researchers used multiple brain and cognitive measures to assess the effects of the diet on brain health, including peripherally collected neuron-derived extracellular vesicles (NDEV) to examine neuronal insulin signaling; MRI to examine the rate of brain aging; magnetic resonance spectroscopy (MRS) to measure brain glucose, metabolites, and neurotransmitters; and NDEV and cerebrospinal fluid to determine biomarkers of Alzheimer’s disease/ADRD.

The study included 40 cognitively fit, overweight, and IR participants, mean age 63.2 years, 60% female, and 62.5% white. Their mean body weight was 97.1 kg, and mean body mass index (BMI) was 34.4 kg/m².

Participants were randomly assigned to an 8-week IF or HL diet that emphasized fruits, vegetables, whole grains, lean proteins, and low-fat dairy products and limited added sugars, saturated fats, and sodium.

The IF diet involved following the HL diet for 5 days a week and restricting calories to one quarter of the recommended daily intake for 2 consecutive days.

Both diets reduced neuronal IR and had comparable effects on improving biomarkers of insulin signaling in NDEV, reducing brain glucose concentrations in MRS, and improving biomarkers of carbohydrate and lipid metabolism in blood.

Using MRI, the researchers also assessed brain age, which indicates whether the brain appears older or younger than a person’s chronological age. The IF diet resulted in a 2.63-year reduction (P = .05) and 2.42 years with the HL diet (P < .001) in the anterior cingulate cortex and ventromedial prefrontal cortex.

Both diets improved executive function and memory, with IF dieters experiencing greater benefits in strategic planning, switching between two cognitively demanding tasks, recalling stimuli, and other areas.

Hypothesis-generating research

AD biomarkers, including amyloid beta 42 (Aβ42), Aβ40, and plasma phosphorylated tau181, did not change with either diet, which the researchers speculate may be due to the short duration of the study. Light chain neurofilaments increased in the groups with no differences between diets.

In other test results, BMI decreased by 1.41 kg/m² with IF diet and by 0.80 kg/m² with the HL diet and a similar pattern was observed for weight. Waist circumference decreased in both groups with no significant differences between diets.

Exploratory analysis showed that women had improved executive function with the IF diet but not with the HL diet, whereas men had improved with both diets. BMI and apolipoprotein E and SLC16A7 Genotypes also modulated the effect of diet.

Both diets were well tolerated. The most common adverse events were gastrointestinal and occurred only with the IF diet.

The authors noted that the results were preliminary and hypothesis-generating. Limitations of the study included the short duration of the study and its ability to detect anything other than large to moderate changes in effect size and differences between diets. The researchers also did not obtain data on dietary intake, so gaps in adherence cannot be ruled out. However, large decreases in BMI, body weight, and waist circumference for both diets indicated high adherence.

The study was supported by the National Institute on Aging, National Institutes of Health. The authors reported no conflicts of interest.