- The brain goes through a variety of changes as we age.
- Some of these changes can lead to age-related cognitive decline.
- There are potential interventions for slowing age-related cognitive decline, including medications and lifestyle changes.
- A new study has found that because of the way the brain gets older, there are certain ages where cognitive decline interventions might be most effective.
As we grow older, every organ in our body — including the brain — ages along with us.
The brain undergoes some changes as it ages, including
Researchers are constantly looking for new interventions to help slow down the progression of age-related cognitive decline, including medications, cognitive stimulation, and lifestyle changes like
Now, a new study recently published in the journal PNAS has found that because of the way the brain gets older, there are certain ages where cognitive decline interventions might be most effective.
For this study, researchers analyzed neuroimaging data of more than 19,000 people from four datasets, including the U.K. Biobank and Mayo Clinic Study of Aging.
Using that data, scientists investigated how the different
“Brain networks are groups of brain regions that communicate with each other to perform specific functions,” Lilianne R. Mujica-Parodi, PhD, Baszucki Endowed Chair of Metabolic Neuroscience, professor of biomedical engineering, and director of the Laboratory for Computational Neurodiagnostics (LCNeuro) at the State University of New York at Stony Brook, and lead author of this study told Medical News Today.
“These networks can be observed using fMRI (functional MRI), which measures blood flow in the brain, and EEG (electroencephalogram), which measures neurons’ activity,” she said.
How aging affects the brain“When these [brain] networks ‘destabilize,’ they become less consistent in their communication patterns over time. Instead of maintaining steady connections, they switch between different configurations, defaulting from ones that are more energy-consuming to those that require less energy to maintain. This switching behavior may reflect a compensatory strategy by the brain to conserve energy when resources are limited, but also has functional consequences for cognition.”
— Lilianne R. Mujica-Parodi, PhD
At the study’s conclusion, researchers found that brain networks degrade in a non-linear way with clear transition points.
For example, they found the effects of the degrading of brain networks is first seen around age 44, with the degeneration hitting peak acceleration around age 67, and then plateauing by age 90.
“In general, physiological systems are tasked with maintaining homeostasis: in this case, a balance between the cell’s energy demands and their energy supply,” Mujica-Parodi explained. “When physiological systems lose the ability to maintain that balance (i.e., they become ‘dysregulated’), it puts stress on the system. That stress itself further disrupts the balance, which is why chronic diseases often are degenerative — they become worse and worse over time.”
“After a point, the system is so disrupted, with so many secondary and tertiary effects, that fixing the original problem no longer helps,” she continued.
A critical age window“Our study suggests that, while diminished access to energy is the driving mechanism, seen in the 40’s, eventually, the degenerative effects compound, thereby accelerating a process in the 60’s that sets the trajectory for a path that is harder to reverse. By analogy, we can think of the brain’s neurons like a bustling city. Each building needs a steady supply of electricity to function properly. When the power grid experiences a brief outage, the town goes dark, but once power is restored, everything returns to normal with no lasting damage.”
— Lilianne R. Mujica-Parodi, PhD
“However, imagine that same city experiencing a prolonged, severe power outage lasting months. Initially, emergency generators keep essential services running, but eventually, those backups fail,” Mujica-Parodi added.
“Water systems stop working, causing pipes to freeze and burst. Buildings deteriorate without climate control, and infrastructure begins to crumble. By the time power is finally restored, significant structural damage has occurred that simply turning the electricity back on cannot fix. Thus, the significance of our finding is that it’s easier to cure a problem while it’s still small,” she explained.
During this study, Mujica-Parodi and her team also discovered that the primary driver of aging brain networks is neuronal insulin resistance, led by an Alzheimer’s risk factor protein called APOE and the insulin-dependent glucose transporter
However, researchers did find that a neuronal
“Neurons can use two types of fuel for energy: glucose (sugar) and ketones (derived from fatty acids). Most neurons in the brain primarily use GLUT3 (not GLUT4) transporters to take up glucose. GLUT4, which is the insulin-responsive glucose transporter found abundantly in muscle and fat tissue, is present in only specific regions of the brain,” Mujica-Parodi detailed.
“This limited distribution of GLUT4 in the brain is significant because it means most brain energy metabolism was traditionally thought to be insulin-independent. However, the neuroscience field is gradually discovering that insulin signaling in the brain is more important than previously believed,” she continued.
Linking ketones and brain aging“When neurons become insulin-resistant, they lose the ability to access glucose as fuel, but not ketones. This means that ketones can function as a ‘back door’ to feeding neurons whose access to glucose would otherwise be blocked by insulin resistance. MCT2 is the primary transporter that enables ketones to enter neurons in the brain. This distribution allows neurons to efficiently uptake ketones when glucose availability is limited, such as during fasting or on a ketogenic diet. Therefore, the presence of MCT2 is essential for the brain’s ability to utilize ketones as an alternative fuel source, which explains why it might be protective as the brain ages.”
— Lilianne R. Mujica-Parodi, PhD
Based on this study’s findings, we asked two experts whether or not following a keto diet might help protect the brain as it ages.
Verna Porter, MD, a board certified neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, told MNT she found the identification of neuronal insulin resistance and the role of metabolic interventions to be very interesting, particularly the potential of ketones, since this may offer a promising direction in the prevention of cognitive decline.
“Based on the findings of the study, the concept of using ketones as an alternative brain fuel is intriguing,” Porter continued. “Ketosis may indeed help protect against cognitive decline by providing neurons with energy when glucose metabolism is impaired.
“[M]ore research is needed to confirm whether a ketogenic diet can consistently be maintained and offer long-term protection, particularly in individuals at risk for Alzheimer’s, and whether it can be effectively incorporated into a broader treatment regimen.”
— Verna Porter, MD
MNT also asked Gary Small, MD, chair of psychiatry at Hackensack University Medical Center in New Jersey for his thoughts on this topic.
“This research not only confirms the importance of early intervention in preventing cognitive decline, but it also elucidates a mechanism for what’s triggering the decline and the therapeutic timing for effective intervention,” Small explained.
“The findings do support the hypothesis that a keto diet during mid-life may be an effective strategy for preventing cognitive decline in late life,” he said.
“A clinical trial of a keto diet that increases insulin resistance in the brain in middle-aged volunteers could lead to a whole new intervention strategy for preventing late-life cognitive decline,” he added.
