Using Antidiabetic Therapies to Treat Alzheimer Disease

Bret S. Stetka, MD; Roger S. McIntyre, MD

Disclosures

August 27, 2015

In This Article

More on Treating Dementia With Insulin

Dr McIntyre: About 5 years ago, we published a paper[4] on individuals with bipolar disorder who were not diabetic. We gave one half of them placebo, and one half of them received intranasal insulin. Intranasal insulin, by going in the nose, goes directly to the brain and doesn't affect your peripheral glucose levels. We found that it helped many patients with their cognitive function performance. It was actually a pro-cognitive intervention.

We just finished a second study in depression, literally within the past 2 months, and we're analyzing the data. Then there's another study[5] by a colleague of mine at Winston-Salem showing that in mild cognitive impairment (MCI) and AD, they are seeing benefits with intranasal insulin compared with placebo on measures of cognitive function.

The other part of this that I think relates is the influence of obesity. The most effective treatment, it seems, for obesity is bariatric surgery. And it's now been shown that bariatric surgery not only causes significant weight loss but also has a very favorable effect on diabetes and heart disease. It also can cause significant improvements in cognitive function,[6] which would be a story in favor of insulin playing a critical role there—because obviously, if you lose a lot of weight, that's going to have a positive effect on your insulin signaling.

Inflammation also appears to play a role here and could be reduced with weight loss. The link between weight loss and a favorable effect on inflammation can be conceptualized as fat cells (ie, adipocytes) producing inflammatory molecules. Inflammatory molecules have a negative effect on the brain and also contribute to insulin resistance. Some of the treatments that are currently being developed—or in most cases, repurposed—for anti-inflammatory central nervous system (CNS) applications are minocycline, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX2) inhibitors, biologics (eg, infliximab), and curcumin (turmeric).

Also, people who lose a lot of weight are more likely to get good night's sleep. Sleep deprivation is potently anti-cognitive. One night of sleep deprivation causes proinflammation and insulin resistance.

Medscape: So are diabetes medications besides insulin being studied in humans?

Dr McIntyre: Yes. We're just started a study at our center looking at patients with depression or bipolar disorder who are not diabetic. We're going to give them the antidiabetic drug liraglutide—one of the newer agents—and use high-resolution MRI to assess its impact on functional efficiency, on cognitive neural networks.

All of this is still experimental, but there is a lot of awareness out there, including on the part of the American Diabetes Association. People now know there's a link between diabetes and AD and are desperate to learn more about the relationship to cognition in general.

Medscape: Do you feel that these medications could help people without diabetes reduce their risk for AD? Could they be using preventively in, say, someone with familial risk for dementia?

Dr McIntyre: Absolutely. I think that in the case of intranasal insulin, we have seen it be effective in people who are not diabetic. In the case of some of these newer-generation antidiabetic drugs, the incretins, we believe that these could help people who have cognitive problems or mental illnesses who are not diabetic. But again, these would have to be given intranasally, so you don't lower the blood sugar in the periphery.

We believe that not just antidiabetics and anti-inflammatory drugs, but any intervention or with anti-inflammatory or antidiabetic effects, could help with cognitive problems or mental disorders. In addition to the agents mentioned earlier, other possible interventions here include mindfulness meditation therapies, sleep normalization, and perhaps even dietary and microbiome interventions.

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