People with type 2 diabetes have an estimated 60% greater risk of cognitive decline and, for older adults with diabetes, double the risk of dementia compared to the general population.

A panel of three experts will examine the links between diabetes and cognitive decline and discuss possible interventions during the Scientific Sessions symposium Dementia and Diabetes—What Are the Causes and How Do We Prevent It? The two-hour session, which will be livestreamed for virtual meeting attendees, will begin at 7:30 a.m. CT Tuesday, June 7, in La Nouvelle Orleans Ballroom C at the convention center.

Auriel Willette, PhD, Iowa State University, will discuss the relationship between obesity, type 2 diabetes, and changes in the brain that reflect accelerated aging or potential Alzheimer’s disease.

“Over 42% of American adults are obese and 25% of them have type 2 diabetes, both of which are major risk factors for Alzheimer’s disease,” Dr. Willette said.

While obesity itself does not seem to affect the parts of the brain responsible for creating or storing memories or facts, which are the areas most heavily impacted by Alzheimer’s disease, Dr. Willette said that obesity does impact the frontal lobe and can lead to problems with higher-order thinking like judgment, juggling multiple tasks, planning, and attention. Weight loss studies suggest that the brain largely recovers in people who were obese and became lean, he said.

“Some of the physiology behind obesity, namely insulin resistance and type 2 diabetes, however, are more problematic. They are not only related to changes in the structure and function of the brain that reflect Alzheimer’s disease, but also more brain pathology we see in Alzheimer’s, namely senile plaques and neurofibrillary tangles,” Dr. Willette said. “Having diabetes and certain genetic risk factors for Alzheimer’s disease can create synergy to vastly increase Alzheimer’s disease risk and impact how the brain functions.”

For 40- to 60-year-old people who present with obesity and type 2 diabetes, Dr. Willette said it’s important to screen for cognitive impairment and ask them if they suffer from brain fog, have difficulty with complex tasks, or other problems specific to the frontal lobe.

“For older people who present with similar symptoms, a cognitive screen should be done in case a referral to a neurologist or psychiatric nurse is needed,” he added. “Patients with dementia risk factors, like a parental family history or having at least one copy of the apolipoprotein E4 (APOE4) variant, may be especially prone to cognitive problems, cognitive decline, and other issues that become more problematic with age.”

Vera Novak, MD, PhD, Beth Israel Deaconess Medical Center, will discuss emerging data suggesting that intranasal insulin may be an effective treatment for cognitive and functional decline associated with aging, insulin resistance, and diabetes.

“Insulin signaling plays a key role in the brain energy metabolism that affects metabolic disorders and cognitive decline,” she said. “Brain insulin resistance, microvascular disease, and impaired insulin signaling are common pathways for cognitive decline in aging, type 2 diabetes, and Alzheimer’s disease.”

Intranasal insulin enters the brain, bypassing the blood-brain barrier, and binds to receptors in multiple cortical regions, the hippocampus, and hypothalamus, thus stimulating dopaminergic and hypothalamic pathways. Intranasal insulin, she said, has been shown to improve verbal memory and has emerged as a potential treatment for cognitive impairment in the elderly.

Dr. Novak will present data from the Memory Advancement with Intranasal Insulin (MemAID) trial, in which she and her colleagues evaluated the long-term effects of intranasal insulin therapy in older people with type 2 diabetes.

Overall, she said that intranasal insulin-treated participants demonstrated better executive function and learning memory, faster walking speed, and decreased insulin resistance. A subset of type 2 diabetes participants had increased cerebral blood flow in the prefrontal cortex. The researchers also found that intranasal insulin was safe and was not associated with serious adverse events or hypoglycemic episodes in the study.

“Intranasal insulin delivery offers a new potential pathway for treatment of age- and diabetes-related cognitive and functional decline,” Dr. Novak said. “With millions of adults worldwide, and an increasing number of younger people having prediabetes, this finding on the beneficial effect of intranasal insulin deserves more attention and definitive confirmation in a larger trial.”

The session’s final speaker, Valory Pavlik, PhD, Baylor College of Medicine, will review the possible mechanisms by which diabetes increases dementia risk and the potential role of multi-modal lifestyle interventions to decrease that risk.

“A recent report by a Lancet commission estimated that 40% of dementia cases worldwide are associated with 12 modifiable risk factors. Among those risk factors is diabetes,” Dr. Pavlik said. “It’s common for persons with dementia to have multiple underlying pathologies, including Alzheimer’s plaques and tangles, vascular pathology caused by strokes, and other types of brain pathology.”

Regardless of the underlying pathology, she said recent evidence suggests that lifestyle interventions can be effective in preserving cognitive function.

“The FINGERS trial from Finland, for example, showed significant cognitive benefit in the active treatment arm after two years from a multi-modal intervention of healthy diet, increased physical activity, and cognitive and social engagement,” Dr. Pavlik said. “Replication of the results of the FINGERS trial in a U.S. population sample would serve as important motivation to persons at risk of dementia to undertake recommended lifestyle changes, and to policymakers to facilitate adoption of dementia-preventing lifestyle changes in the population. Such lifestyle changes would undoubtedly impact diabetes risk as well.”

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