As the average age of people in the U.S. continues to rise, concern about Alzheimer’s disease is increasing.

Another major growing health threat is diabetes. Medical experts at the U.S. Centers for Disease Control and Prevention have warned that diabetes is the fastest-growing chronic disease in the country.

Both Alzheimer’s and diabetes take a sizable toll on human lives and health care resources. And they are strongly related. Diabetes, which attacks the body’s ability to use insulin to control blood sugar, is a risk factor for Alzheimer’s disease. Some researchers have even declared that Alzheimer’s is a form of diabetes that targets the brain. They label it “Type 3 diabetes,” although no professional organization has adopted that term yet.

To better understand the connections between Alzheimer’s disease and diabetes, we spoke with two experts. Dr. Tara Carlisle is a behavioral neurologist and assistant professor of neurology with the University of Colorado Anschutz School of Medicine. She practices at the Advanced Therapy for Neurodegenerative Disorders Clinic, a space within the University of Colorado Neurobehavior and Memory Disorders Clinic at the UCHealth Neurology Clinic – Central Park.

Dr. Dana Dabelea is founder and director of the Lifecourse Epidemiology of Adiposity & Diabetes (LEAD) Center and associate dean of research at the Colorado School of Public Health.

What is insulin resistance, and why is it a threat to good health?

Insulin is a hormone produced by the pancreas that helps the body regulate blood sugar. Insulin resistance occurs in the cells of people with Type 2 diabetes, which increases the risk of their blood sugar rising. The increase in blood sugars to unsafe levels (hyperglycemia) can, in turn, cause problems in many areas of the body.

For example, Dabelea said, insulin resistance that leads to Type 2 diabetes can damage the eyes, kidneys, heart, blood vessels and nerves.

“These are the traditional complications of diabetes,” she said.

Is insulin resistance linked to Alzheimer’s disease?

Yes, insulin resistance is linked to Alzheimer’s disease. Carlisle noted that the brain contains glucose receptors that are an important part of the circuitry that helps us think, remember and learn. Insulin resistance can disrupt the brain’s functioning, just as it does other organs.

“Robust” studies of large populations show that people with Type 2 diabetes have an increased risk of Alzheimer’s disease, she said. Evidence is also mounting that people with Type 1 diabetes — an autoimmune disease that attacks the body’s ability to produce insulin — are also at greater risk for Alzheimer’s disease.

“There seems to be some signal that there is a role in glucose metabolism and Alzheimer’s disease risk,” Carlisle said.

She emphasized, however, that there are many “pathways” other than glucose that can disrupt brain cells from functioning normally. For example, the disruption can occur to the receptors that manage lipids (like cholesterol) and to the mitochondria, which are the “powerhouses” that provide energy to brain cells, she said.

In short, research suggests that in some cases, insulin resistance and these other disruptions of the metabolism may occur “upstream” –— before the brain develops amyloid plaques and tau tangles that are both associated with Alzheimer’s disease — and “increase the risk of these toxic proteins building up,” Carlisle said.

Some researchers suggest using the term ‘Type 3 diabetes’ in recognition of the link between diabetes and Alzheimer’s disease. Is that valid?

Both Dabelea and Carlisle say “no,” it’s not accurate to characterize diabetes in people who also have Alzheimer’s disease as Type-3 diabetes. They note that many other factors increase a person’s risk of getting Alzheimer’s disease. The biggest risk is aging, but the list of risk factors is long and varied and includes high blood pressure, obesity, sleep apnea, smoking, environmental factors like air pollution, alcohol use, hearing loss and depression. Women have about twice the risk of developing Alzheimer’s disease as men.

“We don’t have a clear understanding of the pathways, or whether there are multiple pathways or a sequence of pathways,” Dabelea said. “For sure, there is not a complete overlap between diabetes and Alzheimer’s disease. In other words, not everybody with diabetes will develop Alzheimer’s, which contradicts the term ‘Type 3 diabetes,’ because Alzheimer’s is not a necessary complication of diabetes.”

The same logic applies to other factors associated with Alzheimer’s disease, Carlisle noted. “People who have high blood pressure also have an increased risk of getting Alzheimer’s, but we’re not calling high blood pressure Alzheimer’s disease,” she said. “So, if we try to call Alzheimer’s disease diabetes, we’re oversimplifying the complexity of the risk.”

The bottom line is that we shouldn’t think of Alzheimer’s disease as a single entity, Carlisle added.

“We should be calling it ‘Alzheimer’s diseases,’” she said. “Just as with diabetes, there are multiple forms.”

So, is the term ‘Type 3 diabetes’ useful?

In general, the term “Type 3 diabetes” is not useful for the reasons Dabelea and Carlisle outlined above. Both called the term “sensationalized.” Dabelea acknowledged that the idea has been advanced for at least two decades. One paper published in 2008, for example, declared that “the term ‘type 3 diabetes’ accurately reflects the fact that [Alzheimer’s disease] represents a form of diabetes that selectively involves the brain… .”

Dabelea said that’s a decidedly minority view, noting that Type 3 diabetes is not recognized by the American Diabetes Association, or “the vast majority of clinicians.”

Carlisle added, however, that the term helps to provoke discussion and additional research into the relationship between insulin resistance and Alzheimer’s disease.

“I think that even though the term ‘Type 3 diabetes’ is sensationalized, it comes from a place of understanding what are the things that we can intervene upon as far as dementia risk,” she said.

GLP-1 drugs like Ozempic have been successful in managing Type 2 diabetes and obesity. Could they help to slow cognitive decline?

GLP-1 drugs are not helpful to slow cognitive decline, at least for now. Two recently completed phase 3 clinical trials tested whether semaglutide – the synthetic material in Ozempic and other diabetes and weight loss drugs called GLP-1s – could slow cognitive decline, compared to a placebo, in patients with early-stage Alzheimer’s disease. A total of 3,800 patients participated in the studies, dubbed EVOKE and EVOKE+.

Disappointingly, semaglutide did not do a better job than a placebo of slowing the progression of Alzheimer’s disease. Attendees at the Clinical Trials on Alzheimer’s Disease conference in early December learned the details of the trials.

Carlisle said there was a solid basis for the EVOKE trials. They emerged from studies that showed that, as a group, people with diabetes who took GLP-1 drugs had a lower risk of cognitive decline than those who did not.

Because of that “signal,” researchers took the next step to see if GLP-1 drugs could slow the progression of cognitive decline in patients with mild or moderate Alzheimer’s disease, she said.

Do these disappointing study results mean that GLP-1 drugs have no role in treating Alzheimer’s disease?

These study results don’t necessarily mean GLP-1 drugs have no role in Alzheimer’s disease treatment, said Carlisle, noting that the trial results raise the question of whether GLP-1s might benefit people if taken before cognitive decline has developed. That idea also underscores the importance of treating diabetes and other risk factors for Alzheimer’s disease as early as possible, she said.

“I suspect that there may be some studies in people who have positive Alzheimer’s disease markers, but don’t have cognitive impairment yet, to see whether we can reduce the risk of having that measurable impairment,” Carlisle said. “That’s really where Alzheimer’s research has been moving, and part of that is because we have had so many failed clinical trials in the last 30 years.”

An important aid in reaching that goal is a blood test, approved by the FDA in 2024, for the early detection of biomarkers that indicate an increased risk for Alzheimer’s disease. Previously, detecting these biomarkers required drawing cerebrospinal fluid or having amyloid positron emission tomography (PET) scans.

Carlisle emphasized it is highly unlikely that a single therapy will be the answer to treating or preventing Alzheimer’s disease. She pointed to the multi-prong approach to treating cancer.

“There is probably more than one mechanism that might be contributing to one individual’s risk for Alzheimer’s. Is it neuroinflammation? Is metabolic disruption playing a role? Is it hormonal based? We need to be sure to target these multiple different pathways all at the same time, the way they do with cancer therapeutics,” she said. “We’re behind cancer treatment because we’ve been targeting single pathways so far.”

Are there efforts on the University of Colorado Anschutz Campus to understand the links between diabetes and Alzheimer’s disease?

Yes, there are efforts to understand the links between diabetes and Alzheimer’s disease. One important example: Dabelea and Dr. Allison Shapiro, assistant professor and director of clinical research in the Pediatric Endocrinology Section at the University of Colorado Anschutz School of Medicine, colead a study of the possible links between diabetes and cognitive decline and dementia in young people with Type 2 diabetes.

The small study used blood samples and brain images from the long-running national SEARCH for Diabetes in Youth study. Dabelea serves as principal investigator for the study at the Colorado School of Public Health. The study concluded that the young people had biomarkers for cognitive decline and that the markers increased as the youngsters aged into adulthood.

“These young people might be the candidates for intensive treatment and prevention approaches to prevent full-blown disease,” Dabelea said.

In addition, Dabelea is a leader in the national Diabetes Prevention Program and Outcomes Study, which has followed adults with prediabetes over more than a quarter century. The goal: test whether interventions, including lifestyle changes and the diabetes medication metformin, could more effectively prevent Type 2 diabetes than a placebo. The study also included long-term follow-up to test whether gains from the prevention program were sustained.

Now Dabelea leads an additional study phase that follows older adults with prediabetes, Type 2 diabetes and obesity, with the goal of discovering how these conditions might link to insulin resistance and Alzheimer’s disease. She said she anticipates presenting an abstract of the study findings at the American Diabetes Association professional meeting next summer.

What can individuals do to protect their brain health?

There are many steps people can take to reduce their risk of cognitive decline. Carlisle notes that the Lancet Commission in 2020 identified 12 risk factors (many of them mentioned above) that could “delay or prevent” 40% of dementia cases worldwide. In 2024, the Commission added two more risk factors – vision loss and high cholesterol levels – and increased the percentage of preventable cases to 45%.

Carlisle noted that she and her colleagues offer patients the “Six Pillars of a Brain-Healthy Lifestyle,” which include exercising regularly, getting quality sleep, managing stress, maintaining social connections, seeking mental stimulation and eating a healthy diet, such as the MIND diet.

The 2024 US POINTER randomized trial also supported this approach, concluding that a regimen of regular exercise, the MIND diet, social engagement and mental challenge improved cognition in more than 2,000 older adults at risk of dementia, Carlisle added.

These are all elements that people can choose to control. What, if anything, prevents them from doing so?

Dabelea identified two factors in the Western world that can make it harder for people to manage the factors that contribute to diabetes, high blood pressure, cardiovascular disease and increase the risk of Alzheimer’s disease.

The first is inevitable. “In general, people are living longer, and these are all chronic diseases associated with age,” she said.

Second, she noted that while individuals can make lifestyle choices that promote healthy behavior, sometimes societies are “structurally designed” to make these changes difficult. For example, eating healthily can be expensive. Neighborhoods may not be set up to encourage walking and other exercise that also helps to relieve stress.

“It’s these seemingly simple things that can become complicated,” Dabelea said. “To me, these two things – aging of the population and the imbalance between individual choice and structural factors – are why we see more and more diabetes and other chronic diseases.”

What should patients and families know right now about the connection between diabetes and brain health?

First, diabetes is a risk factor for Alzheimer’s disease. “As with all other complications of diabetes, control of blood glucose, and physical and social activities, are ways to protect our brains from dementia,” Dabelea said. She added that the point also applies to people without diabetes because they, too, are at increased risk of dementia as they age.

Carlisle agreed but emphasized that diabetes is just one of many contributors to brain health – good and bad.

“I think there is an increasing recognition that not every case of Alzheimer’s disease is the same. We need to take a step back and get a better understanding of all the contributors to Alzheimer’s disease,” she said.