By Jennifer Wolff-Gillispie HWP, LC
EDITOR’S SUMMARY: Some experts now refer to insulin resistance in the brain as “type 3 diabetes”—a potential driver of Alzheimer’s disease and other forms of dementia. This metabolic lens reveals how disrupted signaling and chronic inflammation can impair cognition over time. Rooted in modifiable factors like blood sugar regulation, diet, movement, and sleep, this perspective invites a shift from symptom management to prevention and repair—anchored in the body, where mental clarity and resilience take shape.
In recent years, a compelling theory has gained traction in the medical and scientific community—one that challenges conventional thinking about Alzheimer’s disease and even dementia more broadly. This emerging view suggests that these cognitive disorders may not be solely rooted in aging or genetics, but in something much more controllable: metabolic dysfunction. Specifically, researchers are exploring the idea that insulin resistance in the brain—the same mechanism that underlies type 2 diabetes and other metabolic disorders rooted in insulin resistance—may also trigger neurodegenerative processes that lead to forgetfulness, mental decline, and eventually dementia. Insulin resistance occurs when cells no longer respond effectively to insulin’s signals, preventing glucose from entering the cells and building up in the bloodstream. This shift in focus has opened the door to new thinking about the underlying mechanisms of Alzheimer’s—and the possibility of changing its course through early intervention. As Dr. Mark Hyman, functional medicine physician and educator, explains:
“What’s the link between Alzheimer’s and diabetes? Well, new research shows insulin resistance, or what I call diabesity (from eating too many carbs and sugar and not enough fat) is one of the major factors that starts the brain-damage cascade, which robs the memory of over half the people in their 80s, leading to a diagnosis of Alzheimer’s disease. But don’t think too much insulin affects only older folks’ memories. It doesn’t just suddenly occur once you’re older. Dementia actually begins when you’re younger and takes decades to develop and worsen.”
This emerging link between insulin resistance and cognitive decline is gaining traction at a critical moment. Alzheimer’s disease—the most common form of dementia—is no longer a distant threat. It now touches lives on a scale that demands urgent attention. According to a 2021 review titled “Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms”:
“Alzheimer disease (AD) is a chronic degenerative brain disease characterized by memory loss, neurological impairment, and loss of activities of daily living. It is the most common form of dementia and the sixth leading cause of death in the United States. An estimated 5.8 million Americans suffered from AD in 2020 and this number will triple to nearly 14 million people by 2060.”
In the early 2000s, Dr. Suzanne de la Monte, professor of pathology, laboratory medicine, and neurology at Brown University, made a serendipitous discovery that transformed how Alzheimer’s is understood. By experimentally disrupting insulin receptor function in the brain, she observed changes strikingly similar to those seen in Alzheimer’s. “I was like, ‘Oh my gosh, this made Alzheimer’s,’” she recalled.
Her research fueled the idea that metabolic changes—resembling both type 1 and type 2 diabetes—play a central role in Alzheimer’s. In 2005, she coined the term “type 3 diabetes” to describe what she saw as a diabetes-like condition localized to the brain, where insulin resistance impairs cognition and blood sugar regulation. The concept challenged the long-standing theory that Alzheimer’s was driven solely by plaques and tangles in the brain, suggesting instead that insulin resistance and impaired glucose metabolism may be what actually trigger neurodegeneration. Though initially met with skepticism, de la Monte’s work has gained growing support as research increasingly links metabolic dysfunction to cognitive decline.
Despite nearly two decades of ongoing studies, Alzheimer’s remains a formidable challenge, with millions affected worldwide and no cure yet in sight. De la Monte acknowledges the slow pace of clinical progress but remains optimistic about the increasing focus on brain metabolism. She draws a parallel to the discovery of Helicobacter pylori as the cause of stomach ulcers—a once-dismissed theory that ultimately revolutionized treatment—highlighting the importance of continued exploration into Alzheimer’s metabolic roots. To understand how metabolic dysfunction contributes to cognitive decline, start with insulin—the hormone responsible not only for regulating blood sugar, but also for supporting memory, synaptic signaling, and other critical brain processes. When these are disrupted, the risk for Alzheimer’s and other dementias rises. That’s why it’s important to begin with a clear understanding of what these conditions are.
Making Sense of Dementia—and Where Alzheimer’s Comes In
Dementia is an umbrella term for a set of symptoms marked by a decline in cognitive function severe enough to interfere with daily life. These symptoms can include memory loss, impaired reasoning, language difficulties, and changes in behavior. Dementia is not a single disease but a syndrome resulting from various underlying conditions. Alzheimer’s disease, the most common cause of dementia, accounts for 60 to 80 percent of all cases. In 1906, Dr. Alois Alzheimer, a German psychiatrist and neurologist, documented the case of Auguste Deter—a 51-year-old woman with profound memory loss, confusion, and erratic behavior. After her death, he examined her brain and found abnormal clumps (now called amyloid plaques) and tangled fibers (tau tangles). These microscopic changes would become the hallmarks of the condition that later bore his name. His observations laid the groundwork for a century of research into memory, cognition, and neurodegenerative disease.
Alzheimer’s disease has long been characterized by the buildup of amyloid-beta plaques—protein fragments that accumulate between nerve cells—and tau tangles, which are twisted fibers composed primarily of the protein tau found inside brain cells. These changes are believed to contribute to neuron loss and disrupted synaptic connections, both defining characteristics observed in Alzheimer’s cases. The idea that amyloid plaques directly cause the disease gained traction after a 2006 study led by Sylvain Lesné identified a memory-impairing amyloid-beta oligomer known as Aβ*56.
That work, however, is now under serious scrutiny due to evidence of image manipulation and potential data fabrication—casting doubt on one of the most widely cited studies in the field. More recent research suggests that smaller, soluble oligomers (small clusters) of amyloid-beta—rather than the plaques themselves—may be the more toxic agents driving early disease processes, particularly when fueled by insulin resistance and consistently elevated blood sugar. Interest in these oligomers continues, as they are believed to contribute to the gradual deterioration of memory, thinking skills, and the ability to carry out everyday tasks—key indicators that distinguish Alzheimer’s from other forms of dementia. According to “Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms”:
“Insulin resistance increases neuroinflammation, which promotes both amyloid-β–protein deposition and aberrant tau phosphorylation. By increasing production of reactive oxygen species, insulin resistance triggers amyloid-β–protein accumulation.”
While all individuals with Alzheimer’s disease experience dementia, not all dementia stems from Alzheimer’s. Other forms include vascular dementia, caused by impaired blood flow to the brain; Lewy body dementia—marked by abnormal protein deposits (Lewy bodies) that interfere with normal brain function—and frontotemporal dementia, which tends to occur at a younger age than Alzheimer’s and is linked to damage in the brain’s frontal or temporal lobes. Each type has its own pattern of symptoms, progression, and underlying causes.
Currently, the medical community considers Alzheimer’s and other dementias incurable—progressive conditions that worsen over time and cannot be reversed. While non-drug approaches like cognitive stimulation therapy and rehabilitation can help you stay mentally engaged and adapt by using areas of the brain that still function well, the most common treatment path still relies on pharmaceuticals.
While medication may seem like a reasonable approach to an incurable disease, it often comes with side effects—some of which mimic the very symptoms you’re trying to manage, such as confusion, dizziness, and increased risk of falls. But what if treatment could go beyond masking symptoms or merely slowing decline? What if addressing underlying drivers, like insulin resistance, could actually improve cognition—and in some cases, even reverse symptoms? Dr. Dale Bredesen, a physician-scientist specializing in neuroscience at UCLA’s Department of Pharmacology, offers a hopeful perspective:
“So as we looked at Alzheimer’s disease in particular, we could see that in fact, what’s at the heart of Alzheimer’s disease is a molecular switch. And if you ask what’s controlling it, we identified 36 different mechanisms, 36 different things. So for example, if you’re going to get Alzheimer’s, it matters whether you have insulin resistance… It’s different for each person and therefore if you want to be successful in preventing and treating Alzheimer’s disease, it is like having 36 holes in your roof. You need to patch as many as possible to have an effect. And in fact, we’ve published, we were the first to publish improvement in patients with Alzheimer’s disease and pre Alzheimer’s.”
A deeper look at how the brain processes energy
Insulin is produced in the pancreas—a gland near the stomach—and is vital to nearly every major system in the body. It regulates blood sugar in the liver, fuels muscles, stores energy in fat cells, and promotes vascular health. While it’s best known for managing blood sugar, insulin also plays a crucial—yet often overlooked—role in brain health, sustaining key cognitive processes. Receptors for insulin are densely concentrated in brain regions involved in memory and learning, including the hippocampus and cerebral cortex. These are also the first areas shown to deteriorate in Alzheimer’s disease.
Beyond glucose regulation, insulin supports neurotransmitter signaling, synaptic plasticity, and neuronal protection. Ironically, when brain cells become resistant to insulin and can’t efficiently use glucose for energy, it leads to even more oxidative stress and inflammation. This dysfunction in insulin sensitivity can impair learning, memory, and cellular communication—prompting Alzheimer’s researchers to take a closer look. The implications of this shift are reshaping how prevention and treatment are approached.
While the brain doesn’t rely on insulin to absorb glucose in the same way muscles and fat cells do, it still depends on insulin signaling for a range of critical functions. But when these systems are chronically overloaded—through overeating, diets high in sugar and processed foods, physical inactivity, or ongoing stress—cells begin to ignore insulin’s messages. This resistance gradually disrupts glucose regulation throughout the body and eventually affects the brain as well: starving it of fuel, disrupting communication between neurons, and triggering inflammation and protein buildup—features commonly seen in neurodegeneration and diseases like Alzheimer’s.
Though not yet officially recognized as a clinical diagnosis, the concept of type 3 diabetes opens powerful new pathways for prevention, treatment, and understanding. It suggests that lifestyle strategies aimed at improving insulin sensitivity—like regular exercise, low-glycemic eating, and minimizing medications known to impair glucose metabolism, including statins (which may worsen insulin resistance), antipsychotics, and certain antidepressants—might not only support metabolic health and help manage diabetes, but also protect cognitive function and delay or even halt the onset of dementia. Critics rightly note that Alzheimer’s and other dementias are multifactorial, and reducing them to a single cause like insulin resistance risks oversimplifying a complex, individualized condition. Still, the growing evidence linking metabolic health and brain function points to one clear shift: your approach to cognitive decline may need to evolve—and it may start with how you manage metabolic health as a whole, recognizing its far-reaching effects on the brain.
Understanding tau pathology and disrupted insulin signaling
Multiple interconnected mechanisms contribute to brain insulin resistance, including chronic high blood sugar (hyperglycemia), amyloid-β (Aβ) oligomer accumulation, tau pathology, and chronic neuroinflammation. Aβ peptides—neurotoxic protein clusters—are believed to play a central role in the development of Alzheimer’s disease. In a healthy brain, insulin helps regulate how amyloid precursor protein is processed, which in turn controls the production and clearance of Aβ peptides. But when insulin signaling falters, this balance is disrupted. Insulin resistance triggers increased activity of the enzymes β-secretase and γ-secretase, leading to an overproduction of Aβ peptides.These excess peptides clump together into toxic oligomers that damage neurons.
Worsening the problem, Aβ oligomers can further impair insulin signaling by reducing the number of insulin receptors in the brain and making them less responsive. This creates a self-perpetuating cycle: insulin resistance fuels Aβ accumulation, and Aβ accumulation deepens insulin resistance—contributing to the progressive neurodegeneration seen in Alzheimer’s.
Tau proteins help stabilize the internal structure of nerve cells by supporting microtubules—tiny tracks that transport nutrients and chemical signals within the cell. In Alzheimer’s disease, tau undergoes abnormal changes through a process called hyperphosphorylation, causing the proteins to detach from microtubules and form twisted fibers known as neurofibrillary tangles. These tangles disrupt the neuron’s transport system and interfere with communication between brain cells. Insulin signaling in the brain plays a key role in regulating tau phosphorylation. When the brain becomes insulin resistant, it can increase the activity of an enzyme called glycogen synthase kinase-3 beta, which drives harmful modifications to tau. The result is accelerated tau aggregation and further progression of Alzheimer’s-related damage.
Under healthy conditions, brain cells rely on a cleanup process known as the ubiquitin-proteasome system to identify and break down damaged or misfolded proteins—including faulty tau and amyloid beta. But when this system becomes impaired, these toxic proteins begin to accumulate. Factors that can disrupt this process include chronic high blood sugar, insulin resistance, diabetes, and even certain medications such as nonsteroidal anti-inflammatory drugs, statins (which may interfere with protein degradation pathways), and chemotherapy. As the brain’s ability to clear waste declines, harmful proteins build up, fueling the progression of neurodegenerative diseases.
Persistent neuroinflammation and insulin resistance
Chronic inflammation in the brain—known as neuroinflammation—is a well-established element of Alzheimer’s pathology. It occurs when the brain’s immune cells, including microglia and astrocytes, are repeatedly activated in response to persistent threats like infections, traumatic brain injuries, environmental toxins, or chronic health conditions. While short-term inflammation can be protective, ongoing activation creates a toxic environment that contributes to neuronal damage and cognitive decline. Sustained neuroinflammation is fueled by multiple factors: the buildup of misfolded proteins such as amyloid-beta and tau, systemic inflammation linked to metabolic disorders like type 2 diabetes, and continued exposure to harmful substances in your environment.
These inflammatory processes can weaken the blood-brain barrier, allowing immune cells from the body to enter the central nervous system and intensify inflammation. Understanding how this unfolds is essential, as neuroinflammation plays a central role in the progression of neurodegenerative diseases. In Alzheimer’s and related conditions, harmful signaling molecules known as pro-inflammatory cytokines—such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6—are found at elevated levels. These cytokines don’t just damage neurons; they also interfere with insulin signaling by fueling cellular inflammation. The result is a compounding effect: more oxidative stress, reduced insulin sensitivity in the brain, and accelerated cognitive decline. As neuroinflammation persists, microglia become less effective at clearing harmful amyloid-beta proteins. The resulting accumulation triggers additional damage—deepening a vicious cycle in which inflammation and insulin resistance feed each other, accelerating the progression of Alzheimer’s disease.
Changing Course: Addressing Type 3 Diabetes at the Root
Recognizing the complex interplay between amyloid-beta accumulation, tau pathology, and insulin resistance in the brain highlights the potential of addressing insulin sensitivity as a meaningful therapeutic strategy. By restoring metabolic balance, it may be possible to interrupt the cycle that fuels memory loss and neurological deterioration. This perspective broadens the conversation beyond traditional drug targets like plaques and tangles, inviting interventions that focus on the root-level dysfunction contributing to Alzheimer’s.
One powerful lifestyle strategy to support brain function and improve insulin sensitivity is energizing your brain with ketones—molecules produced by the liver during fat metabolism that serve as an alternative energy source. As Alzheimer’s progresses, the brain’s ability to use glucose for energy declines—but its capacity to use ketones remains largely intact. Ketosis is a metabolic state in which your body shifts from relying on glucose (sugar) to burning fat for energy. In this state, your liver produces ketones, which the brain can readily use for energy. Ketosis reduces your body’s need for insulin, helping improve insulin sensitivity and metabolic flexibility. Ketones like beta-hydroxybutyrate also have anti-inflammatory properties and may support brain function by bypassing the damaged glucose-processing pathways seen in Alzheimer’s. Neuroscientist and author Dr. Sarah McKay writes in “Ketogenic Diets and Brain Health (Part 4)”:
“Research suggests that ketones such as beta-hydroxybutyrate may be a more efficient fuel for neurons than glucose. In particular, ketones increase numbers of mitochondria (cellular “power houses”) in neurons helping them to function more efficiently. Studies have suggested that the ketogenic diet may reduce neuroinflammation. Ketogenic diets increase levels of glutathione – a potent antioxidant. This may protect the brain against oxidative stress that can lead to neuroinflammation and DNA damage.”
One way to supply your brain with ketones—without strict carb restriction—is by using medium-chain triglyceride (MCT) oil, a type of fat derived from coconut or palm kernel oil. Start with one teaspoon per day and gradually increase to one to three tablespoons, as tolerated. MCT oil is rapidly absorbed and converted by the liver into ketones, offering a quick energy source for both brain and body. You can further support low-level ketone production (mild nutritional ketosis) by following a low-glycemic, whole-food diet that includes pastured meats and eggs, wild-caught fish, full-fat dairy (preferably raw), and organic fruits and vegetables. These foods promote metabolic flexibility while supplying the building blocks your brain and body need. A recent study from the University of California, Davis—”Keto Diet Prevents Early Memory Decline in Mice: Molecule From Diet May Play Key Role in Slowing Alzheimer’s Disease”—offered encouraging findings:
“The data support the idea that the ketogenic diet in general, and BHB specifically, delays mild cognitive impairment and it may delay full blown Alzheimer’s disease,” said co-corresponding author Gino Cortopassi, a biochemist and pharmacologist with the UC Davis School of Veterinary Medicine. “The data clearly don’t support the idea that this is eliminating Alzheimer’s disease entirely.”
One key approach to combating type 3 diabetes is daily physical activity, which enhances insulin sensitivity system-wide, supporting both brain and body. Aerobic exercise—such as brisk walking, swimming, or cycling for at least 150 minutes per week—combined with resistance training two to three times weekly, has been shown to stimulate brain-derived neurotrophic factor, enhance insulin signaling, and help clear amyloid plaques associated with Alzheimer’s. Movement that challenges coordination, like dancing or tai chi, can also boost neuroplasticity and support cognitive function. In many ways, exercise acts as a form of medicine, strengthening the brain’s resilience while improving your overall metabolic health.
Equally important is prioritizing restorative sleep and aligning with your body’s natural circadian rhythms. During deep sleep, your brain carries out essential “housekeeping” tasks—clearing amyloid-beta through the glymphatic system and regulating both insulin and glucose metabolism. Maintaining a consistent sleep schedule, even on weekends, and creating a sleep-friendly environment—cool, dark, and quiet—can make a meaningful difference. Reducing screen time and evening blue light exposure, while increasing morning sunlight, helps support melatonin production and restore circadian balance. Together, these sleep habits safeguard brain function and metabolic health, making them a foundational part of any Alzheimer’s prevention strategy.
One of the most transformative—and accessible—approaches is incorporating routine periods of fasting, also known as time-restricted eating or intermittent fasting. Unlike conventional dieting, fasting (along with a ketogenic eating plan) taps into your body’s natural ability to switch from glucose to fat as a primary fuel source. This metabolic shift supports brain health by bypassing impaired glucose pathways and offering a more efficient source of energy. Fasting improves insulin sensitivity, reduces inflammation, and activates cellular repair processes like autophagy, which helps clear damaged proteins and cellular waste. Exactly the kind of help you want when you’re looking to protect your brain.
Growing evidence shows that a daily fasting window of 12 to 16 hours can lead to measurable improvements in both metabolic flexibility and cognitive performance. By simply eating within a consistent time frame each day, you retrain your body’s metabolic rhythm—restoring insulin sensitivity and stabilizing systems that regulate everything from blood sugar to brain clarity. And that rhythmic shift may do more than protect against type 3 diabetes. It may help stall the very cascade of neurodegeneration that leads to Alzheimer’s. Whether you’re facing insulin resistance, cognitive decline, or aiming to prevent them, small daily choices can deliver powerful results.
As Benjamin Franklin famously put it, “An ounce of prevention is worth a pound of cure.” In the case of Alzheimer’s, that prevention may not begin with a pill or procedure—but in your kitchen, your actions, and the routines that shape your days. And while no single habit holds all the answers, the cumulative impact of how you move, rest, eat, and live adds up. In a condition long seen as a matter of fate, possibility returns—not through magic, but through metabolism.
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Published on October 23, 2025.
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