We often see epilepsy and Alzheimer’s disease (AD) as unrelated conditions—one causes seizures, the other memory loss. But in reality, they share more similarities than we once thought. Both involve neuronal hyperactivity, energy deficits, and neuroinflammation. Could a single drug address both conditions at once? Enter metformin—a widely used diabetes medication with unexpected potential in brain health.
Epilepsy – The Firebird That Won’t Rest
Epilepsy is marked by uncontrolled neuronal firing leading to seizures, memory impairment, and long-term damage.
In a healthy brain excitable neuron signals are balanced out by inhibitory neuron signals. When there is a loss of inhibition, as in epilepsy, neurons become hyperexcitable. They fire in rapid, synchronized bursts, disrupting normal brain function (= seizures).
Over time, repeated seizures lead to neurodegeneration and cognitive decline, increasing the risk of dementia.
🔬 The SOZ Region: The Epicenter or Just Another Player?
Neuronal hyperexcitability spreads like an unchecked fire, but is the SOZ region the initial spark (Focal Theory) or just one part of a larger, flammable network (Network Theory)?
If SOZ consistently leads seizure activity, targeting it directly—through drugs or neuromodulation—could suppress seizures at their source. However, if epilepsy arises from a broader landscape of instability, focusing solely on SOZ may not be enough.
Many researchers, including Jean Gotman, supports a network-based approach, showing that seizures don’t always start in one fixed location but often involve multiple brain regions at once. His findings suggest that high-frequency oscillations (HFOs) act as markers for seizure onset zones, helping researchers identify where seizures begin. Additionally, using EEG and fMRI together gives a fuller picture of how seizures spread across the brain. This reinforces the idea that epilepsy is a disorder of widespread network instability rather than a single malfunctioning region.
Rather than a single epicenter, epilepsy may stem from dysfunctional connectivity across brain networks.
Instead, addressing systemic factors like neuroinflammation, energy metabolism, and overall network stability could offer a more effective, long-term approach.
This is where Metformin could be the stabilizing force, regulating both both neuronal excitability and metabolic health—cooling overheated circuits and restoring balance.
Alzheimer’s – The Fading Songbird
Alzheimer’s disease follows a different course but shares key pathological mechanisms with epilepsy. In early AD, inhibitory neurons are often the first to become dysfunctional. This loss of inhibition means neurons fire more frequently, leading to hyperexcitability. Many AD patients experience silent seizures in the brain´s attempt to compensate for weakening connections. Over time, higher neuronal activity leads to more Aß aggregation and toxic buildup of tau protein tangles. These tangles destabilize neurons and promote further degeneration.
The vicious cycle begins: A self-reinforcing loop of excessive firing, Aß buildup, and progressive neurodegeneration.
The Stone: Metformin – A Game Changer?
Originally developed for type 2 diabetes, metformin works by improving insulin sensitivity and activating AMP-activated protein kinase (AMPK)—a key regulator of cellular energy. However, recent research suggests metformin’s benefits extend beyond glucose metabolism to neuroprotection.
How Metformin May Strike Both Birds at Once
✅ Calming neuronal hyperexcitability – Reduces excessive firing, potentially lowering seizure risk and protecting against AD-related neurodegeneration.
✅ Enhancing energy metabolism – Supports mitochondrial function, preventing neuron burnout.
✅ Reducing inflammation – Modulates microglial activation, preventing seizure-induced damage and AD progression.
✅ Boosting cognitive function – Improves spatial memory and learning, suggesting potential therapeutic effects in both diseases.
Could Metformin Redefine How We Approach Neurodegeneration?
Now that metabolic drugs are being explored for brain health, this raises a deeper question: Where does the problem truly lie?
Both Alzheimer’s and epilepsy have increased in the last decade, particularly in the older population. With type 2 diabetes contributing to the risk of both, should we not be looking at our lifestyle, nutrition, and daily habits as the root cause?
💡Click here for more information on this recently published study (24.3.25)
How Type 2 Diabetes Leads to an Energy-Deprived Brain
At first glance, it might seem paradoxical that type 2 diabetes—a condition marked by high blood sugar — could lead to an energy-starved brain. However, the issue lies in insulin resistance.
- Glucose is abundant but unavailable: In type 2 diabetes, cells—including neurons—become resistant to insulin, the hormone responsible for transporting glucose into cells. This means that despite high blood sugar levels, neurons struggle to take in the fuel they need to function.
- Mitochondrial dysfunction: Without adequate glucose uptake, neuronal mitochondria cannot efficiently generate ATP, the cell’s primary energy source.
- Chronic inflammation: High blood sugar levels drive systemic inflammation, worsening neuroinflammation in both epilepsy and AD.
- Increased oxidative stress: Impaired glucose metabolism leads to excessive production of free radicals, damaging neurons and accelerating neurodegeneration.
💡 For more insight on Sugar and the Brain, click here.
Can Lifestyle Be the Ultimate Brain Protector?
Cutting-edge research suggests that our daily habits may hold the key to brain resilience:
🧠 Sleep: The Brain’s Reset Button – Poor sleep isn’t just tiring; it may accelerate cognitive decline. A study by Bennis et al. (2025) found that fluctuations in brain network activity throughout the day predict Alzheimer’s progression.
🏃 Exercise: A Natural Anti-Inflammatory? – Movement isn’t just good for the heart—it may shield the brain. Research by Wang et al. (2025) reveals that treadmill exercise actively modulates neuroinflammatory markers, potentially slowing neurodegeneration.
Could better sleep and regular movement be the simplest tools for preserving brain health?
Final Thoughts: A Pill, a Paradigm Shift, or Both?
Instead of treating epilepsy and Alzheimer’s as separate conditions, metformin targets a shared vulnerability—an overactive, energy-deprived brain. If ongoing research supports its benefits, could it become part of a broader strategy to slow neurodegeneration?
Or does the real solution lie in addressing the lifestyle factors that set the stage for these diseases in the first place?
