Diabetes + Dementia: Using Nasal Insulin to Improve Brain Function

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While obesity is usually associated with type 2 diabetes, the rates of obesity in people with type 1 diabetes are also rising, making this research relevant to both types. The research presented in this session spoke specifically about type 2 diabetes.

Presentation: Dementia and Diabetes: What Are the Causes and How Do We Prevent It?

Speakers at this ADA Scientific Sessions presentation included: Auriel Willette, Ph.D. (Iowa State University), Vera Novak, Ph.D. (Beth Israel Deaconess Medical Center) and Valory Pavlik, Ph.D. (Baylor College of Medicine).

Experts in dementia and Alzheimer’s research expect the cost of managing and treating the growing population of those with these cognitive disorders to increase significantly over the coming decades.

• Global cost of treating dementia: $270 billion annually
• Expected cost by 2050: $1.1 trillion annually

With rising rates of obesity and type 2 diabetes, understanding the impact of these conditions on long-term brain health and function is critical. 

“If we are not able to reduce the cases of dementia,” explained Auriel Willette, Ph.D., “the United States Medicare program could go bankrupt.”

Dementia is a catch-all term for a variety of cognitive conditions, but late-onset Alzheimer’s accounts for about 85 percent of the cases in the United States.

Defined in simplest terms by the shrinking of the brain, Alzheimer’s starts in the temporal lobes and progresses to the frontal and parietal lobes which leads to a massive loss in brain volume. 

This loss of mass leads to a significant decline in memory and overall cognitive function. Declined function can lead to difficulty retrieving both short and long-term memory, as well as accomplishing basic everyday tasks like bathing, eating, making decisions, communicating and much more.

How obesity + type 2 diabetes impact the brain

The research presented shared findings that insulin resistance, prediabetes and type 2 diabetes double your risk of developing Alzheimer’s. There is a large overlap in these conditions:

• 25 percent of people with Alzheimer’s have type 2 diabetes
• 40 to 60 percent of people with Alzheimer’s have prediabetes or insulin resistance (IR)

First, let’s look at obesity—which contributes to insulin resistance and prediabetes, and increases your risk of type 2 diabetes.

• 42 percent of American adults live with obesity
• 19 percent of American children live with obesity

“We know academic performance is lower in obese children,” said Willette. “For individuals who were obese and then became lean, early brain volume loss and cognitive issues appeared to be reversed.”

Obesity’s impact on the brain is similar to the general effect of aging and Alzheimer’s on the brain: volume loss and atrophy in the frontal lobe and prefrontal cortex—both of which drive memory function and “executive function” including regulating emotions, organizing, paying attention, starting and finishing tasks, understanding different points of view and more.

Obesity reduces the brain’s cell-to-cell connectivity. 

Next, combining what we know about obesity with insulin resistance, prediabetes and type 2 diabetes:

Insulin resistance, prediabetes, and type 2 diabetes contribute further to Alzheimer’s in a variety of ways:

• High blood sugar + insufficient insulin levels leave brain cells starved for energy
• High blood sugar levels increase inflammation
• High blood sugar levels damage neurons and surrounding support cells
• Overall lower rate of glucose uptake by the brain for energy
• Overall lower neural network function—largely responsible for retrieving memories

In short, the overall environment created by chronically high blood sugar levels further drives the breakdown and decline of brain function.

Treatment research on obesity, type 2 diabetes (T2D) + Alzheimer’s

Two treatments for Alzheimer’s in people living with obesity, insulin resistance and type 2 diabetes were discussed:

• Intranasal insulin: insulin delivered via the nose straight to the brain
• Lifestyle interventions: focused on physical activity, nutrition, cognitive stimulation

Here is a brief look at both treatments in question.

Intranasal insulin

Not yet FDA-approved, intranasal insulin is delivered to the brain through the olfactory nerve. It is not intended to manage overall blood sugar levels in diabetes. Instead, intranasal insulin shows promise for protecting brain cells from high blood sugar levels.

In ongoing clinical trials using intranasal insulin, the following improvements have been observed in participants with type 2 diabetes who were not on other types of insulin:

• Brain energy and glucose uptake
• Insulin signaling in the brain
• Overall blood flow in the brain
• Functional connectivity (memory function)
• Verbal memory
• Executive functioning
• Physical ability → increased walking pace
• Mobility and decision making skills

The participants did not experience low blood sugars, changes in HbA1c levels, or any notable side effects from treatment.

“Intranasal insulin is a promising new treatment for age, prediabetes and type 2 diabetes-related cognitive and mobility decline,” explained Vera Novak, MD, Ph.D. “Further validation is needed.”

Lifestyle interventions—specifically walking

Simply walking at least two hours per week can significantly improve your cognitive function and prevent cognitive decline according to research presented. 

• After one year of walking at least two hours per week, participants experienced a significant increase in cognitive function
• After one year of walking at least one hour per week, participants maintained existing cognitive function
• Participants who were highly sedentary saw a dramatic decline in cognitive function

The obvious impact of a person’s lifestyle habits on cognitive function and decline have led to the development of The Pointer Study: 

“The Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a two-year clinical trial to evaluate whether lifestyle interventions that simultaneously target many risk factors protect cognitive function in older adults who are at increased risk for cognitive decline. U.S. POINTER is the first such study to be conducted in a large group of Americans across the United States.”

The POINTER study will focus on the following in both self-guided and instructed groups:

• Increasing physical activity → daily walking, etc.
• Eating a healthy diet with more plants, healthy fats, less processed foods, etc. 
• Cognitive stimulation: intentionally engaging in activities like puzzles, trivia, crafts, etc.
• Social stimulation: intentionally interacting with people on a daily basis
• Maintaining regular appointments with your healthcare team for standard care

Experts expressed great excitement in anticipation of early results from the study—hoping to make a difference in the impact of obesity and type 2 diabetes on dementia in the United States.

The study is currently recruiting and welcoming applicants for participation—determine if you are a potential candidate.