A new study suggests that age-related changes in the brain start earlier in life than previously thought, and switching diet may slow down the deterioration.
The findings appear in the journal PNAS.
Hypometabolism occurs when brain cells cannot use glucose as an energy source.
The brain is vulnerable to changes in metabolism.
People with Alzheimer’s disease often experience a severe drop in the brain’s glucose metabolic rate, and the extent of this reduction is associated with the severity of their illness.
Alzheimer’s disease is the most common form of dementia. According to the World Health Organization (WHO), approximately 50 million people globally have dementia, and about 60 to 70% of these have Alzheimer’s disease.
While scientists have been unable to pinpoint why the brain cells stop metabolizing glucose at this point, previous research has shown that a drop in glucose metabolism appears early before Alzheimer’s symptoms develop.
In this study, researchers from the United States and the United Kingdom used the stability of this communication network between brain regions as a way to measure age-related changes in the brain.
They set out to investigate when these changes start and whether a change in a person’s diet from one rich in glucose to ketones could affect the communication between these brain regions.
To determine when these changes to neural stability emerge, the researchers used two large-scale functional magnetic resonance imaging (fMRI) datasets. One dataset came from the Max Planck Institut Leipzig in Germany, and the other from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) in Cambridge, UK. The datasets contained brain scans of nearly 1,000 adults across their life-span (ages 18 to 88).
This type of brain scan measures the stability of brain networks, defined as the brain’s ability to sustain functional communication between its regions.
To investigate how diet affects brain network stability, the researchers used an fMRI machine scanner to measure the neural activity of 42 volunteers under 50 years old.
These volunteers had spent a week following one of three diets: a regular diet, where the primary fuel metabolized was glucose, a low-carbohydrate diet where the primary fuel metabolized was ketones, or a regular diet with an overnight 12-hour fasting.
The researchers measured the volunteer’s ketone and glucose levels before and after the scan.
To ensure that the effect they observed was directly due to glucose or ketones, the researchers carried out a second experiment with 30 volunteers. They asked the participants to consume a calorie-matched glucose or ketone drink after an overnight fast.
The researchers found that the volunteer’s neural networks were destabilized by glucose and stabilized by ketones.
This happened in both the experiments, whether ketosis was generated naturally through a low carbohydrate diet or artificially using ketone supplements.
The researchers found that across a person’s life span, the destabilization of the neural network had links with decreased brain activity and someone’s ability to distinguish between the correct responses to situations known as cognitive acuity.
The study results suggested that changes to the stability of a person’s neural network emerged at 47 years old, and the brain rapidly degenerated from 60 years old onward.
“The bad news is that we see the first signs of brain aging much earlier than was previously thought,” says Mujica-Parodi, a professor in the Department of Biomedical Engineering.
The researcher also has joint appointments in the College of Engineering & Applied Sciences and Renaissance School of Medicine at Stony Brook University in New York and is a faculty member in the Laufer Center for Physical and Quantitative Biology.
“However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons.”
– Prof. Mujica-Parodi
Prof. Mujica-Parodi explained that as people age, their brains lose the ability to metabolize glucose efficiently, causing neurons to starve and brain networks to destabilize.
“This effect matters because brain aging, and especially dementia, are associated with ‘hypometabolism,’ in which neurons gradually lose the ability to effectively use glucose as fuel.”
“Therefore, if we can increase the amount of energy available to the brain by using a different fuel, the hope is that we can restore the brain to more youthful functioning.”
“In collaboration with Dr. Eva Ratai at Massachusetts General Hospital, we’re currently addressing this question, by now extending our studies to older populations,” Prof. Mujica-Parodi adds.
In their paper, the researchers suggest that a ketone supplement would be more appropriate for people with insulin-resistant conditions, such as diabetes, as they are less able to achieve ketosis through a change in diet, fasting, or exercise.
Their findings also support the hypothesis that at least some of the beneficial neural effects reported with a sudden and extreme drop in calories, such as intermittent fasting, may be linked with the brain using ketone bodies as fuel rather than glucose.
The researchers are now working on discovering the precise mechanisms by which fuel impacts signaling between neurons.