• The number of people with dementia worldwide continues to climb, with an expected 139 million people to have it by 2050.
• Certain people are at a higher risk for dementia, including those with type 2 diabetes.
• Researchers have discovered people with type 2 diabetes who took the diabetes drug pioglitazone were less likely to develop dementia later in life.

An estimated 55 million people around the world have dementia, with that number expected to jump to 139 million by 2050.

Certain people are at a higher risk for developing dementia-related diseases, including those with type 2 diabetes.

Now, researchers from Yonsei University in Seoul, Republic of Korea, have discovered people with type 2 diabetes who took the diabetes drug pioglitazone were less likely to develop dementia later in life than those who did not take the drug.

The study was recently published in Neurology, the medical journal of the American Academy of Neurology.

Type 2 diabetes and dementia

Why would a person with type 2 diabetes have an increased risk of developing dementia?

According to Dr. Karen D. Sullivan, a board certified neuropsychologist and owner of I CARE FOR YOUR BRAIN in Pinehurst, North Carolina, diabetes negatively impacts almost every system of the body, including the brain.

“People with type 2 diabetes are between a 50-60% higher risk for the development of dementia than those without diabetes. This is one of the strongest modifiable risk factors for dementia,” she told Medical News Today.

“The insulin resistance we see in diabetes promotes atherosclerosis and changes energy metabolism, which can lead to microvascular changes in the brain and ultimately a loss of blood flow to networks of neurons,” she explained.

Additionally, type 2 diabetes is correlated with an increased expression of interleukin-6 in the brain, Dr. Sullivan said, which causes inflammation and oxidative stress to start the pathological processes seen in Alzheimer’s disease, the most common form of dementia in older adults.

“Two prospective neuropathological cohort studies suggested that diabetes lowers the threshold for the amount of amyloid beta needed for the development of Alzheimer’s disease in a person with diabetes,” she continued.

“The longer you have had type 2 diabetes and the more poorly controlled the disease, the greater the risk of dementia.”
— Dr. Karen D. Sullivan

16% lower risk with pioglitazone

For this study, researchers used data from the National Korean Health Database of people newly diagnosed with type 2 diabetes who did not have dementia. Over 91,000 participants were followed for an average of 10 years. Of that number, 3,467 people received the drug pioglitazone.

Upon analysis, researchers found 8.3% of the people taking pioglitazone developed dementia, compared to the 10% of people with type 2 diabetes who did not take the drug.

After accounting for certain lifestyle factors, scientists found people with type 2 diabetes who took pioglitazone were 16% less likely to develop dementia later in life.

Researchers did mention this study’s limitation as it is based on information on insurance claims, so it is possible some people did not take pioglitazone even if it was prescribed to them.

There is also no information in the study on the severity of the disease, the participant’s glycemic control, or their genetic risk of dementia.

How blood vessels may play a role

When asked how pioglitazone helps lower the risk of a person with type 2 diabetes developing dementia, Dr. Eosu Kim, a professor in the Department of Psychiatry in the College of Medicine at Yonsei University in Seoul, Republic of Korea, and the lead author of this study, pointed out this study was to investigate the association between pioglitazone use and incidence of dementia, not how — with what mechanisms — this drug can suppress dementia pathology.

“However, based on [the] basic pharmacological actions of this drug and findings from previous studies, several could be suggested,” he told Medical News Today.

“First, basically, controlling blood sugar levels is beneficial to brain functions. And this drug improves cells’ metabolic ability and makes them use bio-energy more efficiently — that is, to improve insulin resistance of the brain,” he elaborated.

“Second, some studies have shown that pioglitazone eliminates toxic proteins called beta-amyloid from the brain. Accumulation of beta-amyloid in the brain is one of the main causes of Alzheimer’s disease,” he continued.

“Third, as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s anti-dementia action may be related to improving blood vessel health,” he added.

Strongest protection in heart disease patients

Speaking of the heart, during the study Dr. Kim and his team found the strongest dementia protection benefits from pioglitazone to be among people with type 2 diabetes who had also had an ischemic stroke or ischemic heart disease.

Researchers found those with a history of ischemic heart disease had a 54% reduced risk of developing dementia, and those who had an ischemic stroke had a 43% risk reduction.

Dr. Kim said he and his team were surprised by these results.

“It was an unexpected finding,” he said.

“Ischemic heart or brain diseases are another important risk factor of dementia, so it would have seemed natural if the effect of pioglitazone were found to be diminished in those with such problems. However, the result was opposite to this expectation,” he explained.

Anti-diabetic drugs against dementia

For the next steps in this research, Dr. Kim said they are conducting research to see how currently used anti-diabetic drugs or drug candidates that improve cell energy metabolism can suppress dementia pathology through animal studies.

“In clinical studies, prospective studies are necessary to confirm [the] anti-dementia effects of this drug and risk-benefit balance of using this drug. That is, [a] balance between side effects and beneficial effects of long-term use of this drug in terms of dementia prevention,” he explained.

When asked what she would like to see in the next steps of this research, Dr. Sullivan said the next step for pioglitazone would be to assess long-term safety in humans and identify the optimal dose that reduces side effects but maintains the benefits observed.

Pioglitazone is currently a second-line choice for the treatment of type 2 diabetes due to safety concerns. It is known to increase the risk of fractures, weight gain, and hospitalization for heart failure.

Until then, Dr. Sullivan said the most important thing people with type 2 diabetes can do to help lower their dementia risk is to stabilize their blood glucose levels, as both high (hyperglycemia) and low blood sugar (hypoglycemia) can damage blood vessels in the brain.

“We want patients to avoid the big highs and the big lows — that’s when brain damage happens,” she said.

“Other evidence-based recommendations include doing aerobic exercise for 30 minutes each day (for) five days each week, eating an anti-inflammatory diet, avoiding carbohydrates, prioritizing hydration, maintaining a healthy weight, and managing other vascular risk factors like hypertension, sleep apnea, and high cholesterol.”
— Dr. Karen D. Sullivan

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