Past research shows that people with type 2 diabetes have an increased risk of developing dementia.
Additional research found that people with diabetes have a 73% increased risk of developing any type of dementia, a 56% higher chance of having Alzheimer’s disease, and a 127% increased probability of developing vascular dementia.
Now researchers from the University of California, Los Angeles, The University of Arizona, and Phoenix VA Health Care System have found evidence that an older class of type 2 diabetes medication known as glitazones helps reduce a person’s dementia risk by 22%.
This study recently appeared in the journal BMJ Open Diabetes Research & Care.
Glitazones, also known as thiazolidinediones (TZDs), are medications used to manage and treat type 2 diabetes by targeting a person’s insulin resistance.
This medication targets the peroxisome proliferator-activated receptor gamma (PPAR-gamma) in the body. The PPAR-gamma receptor is responsible for how sensitive a body is to insulin, and also aids in the body’s metabolism of glucose (sugar).
TZDs work by boosting a person’s sensitivity to insulin, helping to make sure their pancreas can continue to produce a normal level of insulin for their body.
Potential side effects of glitazones include:
There are currently two main types of TZD medications. Rosiglitazone, marketed under the brand name Avandia, was originally approved by the Food and Drug Administration (FDA) in 1999, and by the European Medical Agency (EMA) in 2000.
However, the EMA suspended the use of rosiglitazone, and the FDA announced new restrictions and label changes in 2010 following concerns over cardiovascular risks with the drug.
The other type of TZD, pioglitazone, marketed as Actos, is approved for use in the United States and the European Union.
According to the study authors, type 2 diabetes and dementia share similar physiological patterns. For example, past studies show people with diabetes have changes in brain structure and cognitive capabilities similar to those found in dementia.
“At the Center for Innovation in Brain Science [CIBS], we take a multiprong approach in understanding ways to mitigate and prevent the development of Alzheimer’s Disease and other age-related neurodegenerative diseases,” commented Dr. Kathleen Rodgers, associate director of translational neuroscience at CIBS, and professor of pharmacology at The University of Arizona, and a member of the study research team.
“Diabetes is a risk factor for the development of Alzheimer’s disease and initiating factor in the pathogenesis of Alzheimer’s disease is bioenergetic dysregulation. As type 2 diabetes at its base, due to reduced insulin sensitivity, bioenergetics dysregulation, evaluation of drugs that help diabetics properly handle glucose seemed to be an approach to meet our mission at CIBS.”
– Dr. Kathleen Rodgers
For that reason, Dr. Jin J. Zhou, associate professor in the Division of General Internal Medicine and Health Services Research for the Department of Medicine Statistics Core at UCLA and lead author of this study, told Medical News Today there have been investigations of the use of anti-diabetic medications for dementia, especially for Alzheimer’s disease prevention and treatment.
However, the results have not been consistent, leading to her team’s current study.
For this study, Dr. Zhou and her team examined the electronic health records of more than half a million people diagnosed with type 2 diabetes through the national Veteran Affairs (VA) Health System over a 19-year period.
Upon analysis, researchers found after at least 1 year of drug treatment, patients who received TZD only had a 22% lower risk of developing dementia from any cause. Scientists also found these patients lowered their Alzheimer’s disease risk by 11% and vascular dementia risk by 57%.
“Our findings provide evidence for medication selections for mild or moderate type 2 diabetes patients who are at high risk for dementia,” says Dr. Zhou states.
“This,” she told MNT, “may lead to the future study […] [of the] mechanistic of [TZDs]. As our study is an observational study, further validation in other cohorts, including golden standard clinical trials, [is] needed.”
MNT also spoke with Dr. David A. Merrill, a psychiatrist, and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA, about this study.
He was glad to see researchers taking a second look at medications that are generic, available, and affordable as a potential benefit for older adults at risk for memory loss with aging.
“We’ve known for 20-odd years that this type of diabetes medication could be helpful for dementia risk reduction, and these new findings are hopefully renewing interest in pursuing these drugs for dementia prevention and treatment,” Dr. Merrill added.
Because the underpinnings of dementia symptoms are multifactorial, Dr. Merrill said glitazones help address some of the major drivers of dementia, including insulin resistance, atherosclerotic heart disease, and inflammation.
He explained:
“As you address things like metabolism, vascular disease, [and] inflammation, you’re then lowering or slowing the progression of pathologic brain disease, like plaques and tangles and Alzheimer’s. And so by treating general health conditions that we think of as systemic, you end up protecting the brain against age-related dementia.”
As for the next steps in this research, Dr. Merrill said he would like to see more real-world applications of these drugs, as well as combining glitazones with other types of treatments, such as a healthy lifestyle.
“We know that a healthy lifestyle is one of if not the most powerful interventions to reduce [the] risk of dementia,” he detailed. “If you combine a multimodal lifestyle intervention where you’re targeting improvement of a healthy lifestyle, and then you pair that with a drug like a glitazone, you might see a real synergy, as opposed to just using the pill or just advocating for a healthy lifestyle.”



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