The best time to prevent age-related cognitive decline and how to do it

New research suggests that brain aging begins in midlife, but early lifestyle changes and targeted interventions can help prevent cognitive decline.

Translated from The Epoch Times - an article by ZENA LE ROUX, April 27, 2025.

The neurons in our brain are like a bustling city, where every building depends on a steady flow of electricity to function. In the event of a brief power outage, systems are in place to restore the situation, without any damage.

But what if a power outage lasted for months? Backup generators can keep essential services running, but they eventually fail. Water systems could freeze and burst, buildings deteriorate, and infrastructure begin to crumble. By the time the power finally returns, the damage will be done—the city will be in ruins.

Lilianne Mujica-Parodi, lead author of a March study on brain aging patterns and interventions, echoes the above analogy, saying, “It’s easier to fix a problem while it’s still small.”

The study showed that aging follows a specific progression, with the first stage occurring in middle age and coinciding with greater insulin resistance.

Just as a city suffers lasting damage when power is restored too late, the brain can reach a point where intervention is no longer effective. That's why it's essential to act quickly.

The Aging Brain

According to Lilianne Mujica-Parodi, director of the Laboratory for Computational Neurodiagnostics at Stony Brook University, the brain undergoes distinct stages of decline: it remains stable until the mid-40s, when degenerative changes begin, and accelerates sharply around the mid-60s.

One of the key factors in brain aging is reduced glucose metabolism: the brain has difficulty using carbohydrates as an energy source, impairing its function. These metabolic changes begin decades before symptoms appear but often go unnoticed until the later stages of aging, when interventions are much less effective. However, functional magnetic resonance imaging and electroencephalogram – tools used to study brain activity – can detect early age-related brain changes, offering the possibility of prevention rather than treatment at a later stage.

According to Lilianne Mujica-Parodi, understanding the mechanisms of the disease is the first step toward effective treatment. For example, Alzheimer's disease has long been attributed to the accumulation of beta-amyloid, a protein that forms sticky plaques between brain cells, and tau proteins, which form twisted tangles within brain cells. This has led to the development of drugs aimed at eliminating these proteins. However, these treatments have largely failed.

One reason for this failure is that, by the time Alzheimer's disease is diagnosed, irreversible neuronal damage has already occurred. The protein accumulation is a consequence of insulin resistance in the brain—in other words, by targeting beta-amyloid and tau proteins, the drug does not address the root cause.

Unlike many other cells, adult neurons have a very limited capacity for regeneration. If cognitive decline is indeed due to neurons being starved, as the study suggests, waiting until they are unable to function or are dead is unlikely to be effective, according to Mujica-Parodi.

Physiological systems are designed to maintain homeostasis—the balance between energy supply and demand. When this balance is disrupted, the resulting stress can lead to further disruption, exacerbating the problem over time.

When disruptions accumulate and secondary effects such as metabolic stress and glucose dysregulation set in, simply addressing the initial problem is no longer enough.

Insulin Resistance, a Key Factor

The first significant change in brain network instability occurs alongside increasing insulin resistance, often measured by HbA1c, a marker of long-term blood sugar levels.

Neurons rely on two main energy sources: glucose and ketones. While some neurons require insulin to access glucose, those that become insulin resistant have difficulty using this fuel, a condition known as "insulin resistance," explained Lilianne Mujica-Parodi.

When cells lose their ability to efficiently use glucose, their main energy source, metabolic stress increases, slowing the transmission of messages between nerve cells and contributing to cognitive decline.

In conditions such as Alzheimer's disease, glucose uptake and utilization are impaired. This is why Alzheimer's disease is sometimes considered type 3 diabetes, Angel Planells, a registered dietitian nutritionist, explained to The Epoch Times.

When neurons become insulin resistant, they lose their ability to access glucose but can still use ketones, which don't require insulin for metabolism and are an alternative energy source, said Lilianne Mujica-Parodi.

Even in older adults with mild cognitive impairment or Alzheimer's disease, it has been shown that brain cells can still absorb ketone bodies, although at this stage, irreversible damage can limit their effectiveness.

This is why it is essential to identify windows of intervention to proactively protect the brain.

Windows of Intervention

"Age-related cognitive decline is not an inevitable consequence of aging, but rather a process that can be prevented through early interventions targeting insulin resistance in the brain," said Lilianne Mujica-Parodi.

Brain aging follows a predictable trajectory. Unlike a gradual, linear decline, these changes occur in an "S"-shaped curve, suggesting specific windows during which interventions may be most effective.

The average brain becomes more unstable over time, but metabolic interventions can reverse this. (Epoch Times)

Beginning in the late 40s, brain networks undergo significant changes marked by instability and loss of coordination. These changes are similar to those observed in people with type 2 diabetes, reinforcing the idea that insulin iresistance is a major factor in early cognitive decline.

The period between ages 40 and 60 is the most critical for intervention. During this period, brain networks are more unstable but still adaptable, making it an optimal time for interventions.

Keto Diet

Metabolic interventions that quickly overcome insulin resistance have proven effective, such as ketone supplementation or adopting a ketogenic diet.

Lilianne Mujica-Parodi was surprised by the rapid effect of these interventions—in her studies, brain networks stabilized within 30 minutes of consuming a ketogenic drink.

In one study, participants were given a ketone or glucose drink after an overnight fast, and their brain activity was measured using functional magnetic resonance imaging to observe any changes. It was found that the functioning of brain networks changed depending on the fuel source: glucose reduced stability, while ketones increased it. This effect was observed with both dietary changes and ketone supplements, showing that the brain switches networks to conserve energy when resources are limited. A previous study also showed similar changes after just one week of a ketogenic diet.

Ketones can be produced in the body through low-carb, high-fat diets or fasting, or can be taken in supplement form, but brain health doesn't necessarily have to wait until midlife. Early lifestyle changes, such as adopting a low-carb, high-fiber diet and regular physical activity, can help prevent or delay insulin resistance in the brain, Mujica-Parodi said.

After midlife, screening for insulin resistance in the brain—beyond standard HbA1c measurements—could identify risks early enough to implement ketogenic diets or supplements to promote glucose access.

"Not everyone needs a strict ketogenic diet," Planells said. "But reducing processed carbohydrates and improving insulin sensitivity are generally beneficial for brain health."

It's worth noting that despite their potential benefits, ketone supplementation and the ketogenic diet have limitations. For some, the restrictive nature of the ketogenic diet can reduce adherence, while ketone supplementation can cause side effects such as gastrointestinal disturbances, headaches, or electrolyte imbalances.

In addition to ketogenic diets and supplements, cognitive resilience—the brain's ability to adapt to stress and maintain function—can also be strengthened through activities such as mentally stimulating tasks, learning new skills, and maintaining social connections, Planells advised. Chronic stress and elevated cortisol levels can accelerate brain aging, which is why mindfulness practices, such as meditation, are beneficial, he said.

"The window of opportunity may be narrow, but knowing it exists empowers us," he said.