The possible complications posed by diabetes—heart disease and damage to eyes, feet, nerves and so forth—are fairly familiar to the general public. But in recent years, scientists have been scrutinizing a risk that is both less well known and less understood—the heightened likelihood of dementia.
Researchers have known for several years about diabetes and the higher risk of vascular dementia, the second most common kind. In ways, it seems only logical: Vascular dementia is caused by damaged blood vessels in the brain, just as diabetes hardens blood vessels elsewhere.
The latest research is focused on Alzheimer’s disease, the most common neurodegenerative disorder and one for which it’s harder to figure out the precise relationship with diabetes. On this much, many scientists agree: The rate of Alzheimer’s disease could be cut by close to half if diabetes could be abolished. The connection between the two is so strong that Suzanne M. de la Monte, one of the top researchers in the field, has said that many cases of Alzheimer’s could be dubbed Type 3 diabetes.
People who haven’t necessarily developed diabetes might still develop insulin resistance in the brain, said de la Monte, a professor of neurosurgery, pathology and laboratory medicine at Brown University. That’s why she uses the term Type 3 diabetes—one doesn’t necessarily cause the other. But in both cases, she said, people show certain markers at the cellular level.
“Growing evidence supports the concept that Alzheimer’s disease is fundamentally a metabolic disease with molecular and biochemical features that correspond with diabetes mellitus and other peripheral insulin resistance disorders,” de la Monte wrote in 2014 in the journal Biochemical Pharmacology. But the picture is more complicated than that, she wrote, because Alzheimer’s “can occur as a separate disease process, or arise in association with systemic insulin resistance diseases, including diabetes, obesity, and non-alcoholic fatty liver disease.”
A 2015 pilot study published in the Journal of Alzheimer’s Disease found that doses of nasal insulin—bypassing the blood/brain barrier—significantly improved memory in people with early Alzheimer’s disease and mild cognitive impairment. A larger, five-year clinical trial is now underway.
Inflammatory response appears to play a role, de la Monte said. Both diabetes and Alzheimer’s are inflammatory diseases. And yet, other forms of brain inflammation are not associated with cognitive problems later on.
“Multiple sclerosis, encephalitis, none of these lead to dementia,” she said. “What is the cause of all this, where is the problem? Because Alzheimer’s disease was not that common before. We can link a lot of the extra cases to diabetes and obesity. So if we have that, is it just because people are fatter? I don’t think it’s just that. But then if you talk about metabolic syndrome, fatty liver, PCOS, infertility–how many diseases are linked to the same problem of insulin resistance and an inflammatory process?”
People need a lot more help in learning how to stave off Type 2 diabetes and other metabolic diseases through diet and exercise, de la Monte said. And because testing can find the same precursor conditions for both brain insulin-resistance and diabetes, there’s reason to think more people should be screened earlier, with these more sensitive tests.
Melissa Schilling, a professor at the New York University Stern School of Business, came to a similar conclusion after conducting a review of the relationship between diabetes and Alzheimer’s.
Her 2016 paper in the Journal of Alzheimer’s Disease estimated that 40% of all Alzheimer’s cases were connected to hyperinsulinemia, or excess levels of insulin relative to glucose in the blood. That would include not just people with diabetes but the 86 million Americans estimated by the CDC to have prediabetes.
“If we can raise awareness and get more people tested for hyperinsulinemia … it could significantly lessen the incidence of Alzheimer’s disease and vascular dementia, as well as other diabetes-related health problems.” Schilling said in a press release.
Research by Margaret Gatz, a professor of psychology at USC, further refined the relationship between the two. She and fellow researchers in Sweden found that not only was diabetes strongly associated with dementia, but that people who are first diagnosed with Type 2 diabetes in middle age, rather than after age 65, are at much higher risk. And that finding was independent of how long people had diabetes before developing dementia—in other words, it was the age at diagnosis, not how long they lived with diabetes, that determined their risk.
At this point, Gatz is particularly interested in the role that stress might play in the equation.
“One theory is I’ve been intrigued by involves the HPA (hypothalamic-pituitary-adrenal) axis,” she said. The HPA axis controls the immune system, digestion—and reactions to stress. “It’s what fires when someone is stressed,” Gatz said. “After it’s heavily activated, it might potentiate diabetes and hippocampal damage, inflammation and oxidative damage.
“Maybe this whole stress process is basically inflammatory damage, oxidative damage.”
She agreed that earlier, more sensitive testing might warn people away from the kind of eating and sedentary habits that can cause prediabetes and diabetes. Stress management might be part of the picture, too, she suggests.
“I’m heavily a physical exercise proponent. When people ask me, ‘What’s the biggest thing I can do to avoid dementia?’ my answer is exercise. But also workplaces are more stressful, people describe themselves as not handling stress as well. All of these are risk factors.”
At Brown, de la Monte is planning to publish a paper that looks at what kinds of testing might best be used as early indicators of future dementia. “We’re looking at peripheral markers that indicate brain disease,” she said. “If you look at blood, can you find evidence of inflammation in people who have no inflammatory disease but they have mild cognitive impairment and they also have markers of insulin resistance? We can pick out from that who is at risk. At least to inform them so they can start using lifestyle measures.”