The neurons in our brain can be likened to a complex and vibrant city, where each structure relies on a continuous supply of electricity to maintain proper function. In the case of a brief power outage, contingency systems are typically sufficient to restore operations without lasting consequences.
However, should the power failure persist for several months, even the most robust emergency systems would eventually falter. Water systems could freeze and rupture, buildings would deteriorate, and the underlying infrastructure would begin to decay. By the time power is restored, the city would have already suffered irreversible damage.
Lilianne Mujica-Parodi, lead author of a March study examining brain aging patterns and potential interventions, employed this analogy to underscore a critical insight: “It’s easier to cure a problem while it’s still small.”
The study revealed that brain aging follows a predictable trajectory, with the initial phase beginning in midlife and coinciding with an increase in insulin resistance.
Much like a city that suffers lasting damage when power is restored too late, the brain may reach a point where therapeutic intervention is no longer effective. This underscores the importance of early action.
The Aging Brain
According to Lilianne Mujica-Parodi, Baszucki Endowed Chair of Metabolic Neuroscience and Director of the Laboratory for Computational Neurodiagnostics at Stony Brook University, the brain experiences distinct phases of decline. It remains relatively stable until the mid-40s, when degenerative changes begin to manifest, and then declines more rapidly by the mid-60s.
A central factor in this process is reduced glucose metabolism—where the brain becomes less efficient at utilizing carbohydrates for energy, impairing overall function. These metabolic shifts often commence decades before the onset of noticeable symptoms, making them difficult to detect in their early stages. Nevertheless, advanced imaging technologies such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) can identify early neurophysiological changes, offering an opportunity for proactive intervention rather than delayed treatment.
Understanding the underlying mechanisms of disease is essential for developing effective therapies, Mujica-Parodi explained. Alzheimer’s disease, for instance, has traditionally been attributed to the accumulation of beta-amyloid plaques and tau protein tangles within the brain. As a result, drug development efforts have largely focused on clearing these proteins. However, these approaches have had limited success.
One possible reason for these failures is that by the time Alzheimer’s disease is clinically diagnosed, substantial and irreversible neuronal damage has already occurred. The buildup of amyloid and tau proteins is not the root cause, but rather a downstream effect of insulin resistance within the brain. Thus, treatments aimed solely at removing these proteins do not address the underlying metabolic dysfunction.
Unlike many other cell types, mature neurons possess minimal regenerative capacity. If cognitive decline is the result of neurons effectively starving—due to impaired energy metabolism—then waiting until these cells are compromised or lost renders treatment largely ineffective, Mujica-Parodi emphasized.
Physiological systems are inherently designed to maintain homeostasis, a delicate equilibrium between energy supply and demand. When this balance is disrupted, the resulting stress can initiate a cycle of dysregulation, exacerbating the condition over time.
As disruptions accumulate and secondary effects—such as metabolic stress and glucose dysregulation—take hold, addressing the original cause alone becomes insufficient for recovery.
Insulin Resistance as a Key Driver of Cognitive Decline
The initial major disruption in brain network stability coincides with increasing insulin resistance, commonly assessed through HbA1c—a biomarker indicating long-term blood glucose levels.
Neurons primarily depend on two sources of energy: glucose and ketones. While some neurons require insulin to effectively absorb glucose, those that develop insulin resistance lose the ability to utilize this fuel efficiently, a condition known as “insulin resistance,” explained Lilianne Mujica-Parodi.
As these neurons become less capable of metabolizing glucose—the brain’s primary energy source—metabolic stress intensifies. This impairs neural communication, slows signal transmission between neurons, and contributes to progressive cognitive decline.
In neurodegenerative disorders such as Alzheimer’s disease, glucose metabolism is markedly impaired, which is why Alzheimer’s is sometimes referred to as “Type 3 diabetes,” noted Angel Planells, a registered dietitian nutritionist based in Seattle, in an interview with The Epoch Times.
However, even when neurons lose the ability to metabolize glucose due to insulin resistance, they retain the capacity to utilize ketones—an alternative energy source that does not rely on insulin. Mujica-Parodi emphasized that this metabolic pathway remains viable, even in individuals with mild cognitive impairment or early-stage Alzheimer’s disease. Nevertheless, once significant neuronal damage has occurred, the benefits of ketones may be limited.
This highlights the critical importance of identifying optimal windows for intervention—when the brain is most responsive to preventative measures.
Windows of Intervention
“Cognitive decline associated with aging is not an unavoidable outcome of growing older, but rather a process that may be mitigated through early interventions targeting insulin resistance in the brain,” said Mujica-Parodi.
Brain aging follows a defined trajectory. Rather than progressing in a steady, linear fashion, it tends to follow an “S-shaped” curve—indicating that there are distinct periods during which interventions may yield the greatest benefit.
Beginning in the late 40s, brain networks begin to exhibit instability and diminished coordination. These patterns closely mirror the changes observed in individuals with Type 2 diabetes, further reinforcing the role of insulin resistance in early cognitive decline.
The period between ages 40 and 60 represents the most critical window for intervention. During this time, although brain networks become increasingly unstable, they remain highly adaptable—making this stage particularly responsive to preventative strategies.
The Role of Ketogenic Interventions
Metabolic approaches that bypass insulin resistance—such as ketone supplementation or adherence to a ketogenic diet—have demonstrated promising results.
Mujica-Parodi expressed surprise at the rapid efficacy of these interventions. In her research, the administration of a ketone supplement led to measurable stabilization in brain network activity within just 30 minutes of consumption.
Fueling the Brain: Glucose vs. Ketones
In one study, participants were administered either a ketone-based or glucose-based beverage following an overnight fast. Researchers then monitored brain activity using functional magnetic resonance imaging (fMRI) to assess changes in neural network function. The findings revealed that the brain’s network stability varied depending on the type of fuel it received: glucose intake decreased stability, while ketone intake enhanced it. These effects were observed not only through dietary changes but also with ketone supplementation, indicating the brain’s adaptive response to limited energy resources—shifting network activity in an effort to conserve energy. A prior study corroborated these results, showing similar improvements in brain network stability after only one week on a ketogenic diet.
Ketones can be generated endogenously through low-carbohydrate, high-fat diets or fasting, or introduced exogenously through supplements. However, the importance of brain health extends beyond middle age. According to Mujica-Parodi, early lifestyle interventions—such as adopting a lower-carbohydrate, higher-fiber diet and engaging in regular physical activity—can play a preventive role by reducing the risk of developing insulin resistance in the brain.
By the time individuals reach their 40s, more advanced screening for brain-specific insulin resistance—beyond standard HbA1c testing—may help detect early risk. This can allow for timely implementation of targeted interventions, including ketogenic diets or supplementation, to support cognitive function by maintaining access to alternative energy sources.
“Not everyone requires a strict ketogenic diet,” noted Angel Planells. “However, minimizing processed carbohydrate intake and improving insulin sensitivity generally provides broad benefits for brain health.”
It is important to acknowledge that, despite their potential advantages, both ketogenic diets and ketone supplements have limitations. The highly restrictive nature of the ketogenic diet may hinder long-term adherence, and ketone supplements may cause side effects in some individuals, such as gastrointestinal discomfort, headaches, or electrolyte imbalances.
In addition to nutritional strategies, cognitive resilience—the brain’s capacity to adapt and maintain function under stress—can be strengthened through intellectually stimulating activities, learning new skills, and fostering social engagement. Chronic stress and elevated cortisol levels can accelerate cognitive decline, which is why mindfulness-based practices, such as meditation, are also recommended, Planells added.
“The window of opportunity may be narrow,” he said, “but knowing it exists empowers us to act.”