Your Brain and Diabetes

By Brett Goerl and Matthew Garza

Recent studies have shown a link between brain diseases like Alzheimer’s and Parkinson’s and diabetes. Unfortunately, these conditions are becoming more common as our population grows older. Find out ways to improve brain health.

What are neurodegenerative diseases?

The term “neurodegenerative diseases” refers to a range of diseases in which the cells in our brains break down and can no longer perform their designated functions associated with movement or mental ability, according to the EU Joint Programme – Neurodegenerative Disease Research. The most common neurodegenerative diseases that affect people with diabetes are mild cognitive impairment (MCI) and dementia, which includes Alzheimer’s disease. 

As we age, it is completely normal for our memory, thinking, and judgment to slightly decline. However, MCI occurs when our mental abilities decline faster than expected and begin to interfere with our daily lives. Age is by far the biggest risk factor for MCI, but diabetes, smoking, high blood pressure and cholesterol, obesity, and depression can further increase a person’s risk of developing MCI.

In around 10-15% of cases each year, the mental decline seen in MCI may progress further, making it difficult for us to carry out a healthy and happy life. When this happens, it is called dementia. The two most common types of dementia that affect people with diabetes are Alzheimer’s disease (AD) and vascular dementia.

While the symptoms of AD and vascular dementia are similar, they are caused by two different processes that occur in our brains. AD is thought to be caused by the abnormal build-up of proteins in the brain. One protein is “amyloid,” which clumps together in spaces around brain cells. The other protein is “tau,” which get tangled up inside brain cells. Vascular dementia, on the other hand, occurs when the blood vessels in our brain become narrow or start to bleed. This reduces the brain’s ability to get the oxygen it needs to keep brain cells healthy and for the brain to function properly. In both cases, brain cells become damaged, leading to a wide range of problems such as memory loss, worsened judgment, and personality changes. 

AD is the most common form of dementia in the US, making up 60-70% of dementia cases. In the US, an estimated 5.4 million people of all ages are affected by AD, and one in eight people 65 years and older suffer from it. Considering the 14.3 million adults aged 65 and older in the U.S. who have diabetes, and it is easy to see why Alzheimer’s disease and diabetes are two of the most common diseases of aging. And recent research has suggested that they may be linked in various ways.

How do neurodegenerative diseases like Alzheimer’s and vascular dementia relate to diabetes? 

We often think of diabetes as a problem with our metabolism since the lack of insulin (in type 1 diabetes) or insulin resistance (in type 2 diabetes) affects our body’s ability to maintain normal blood glucose levels. However, our brain consumes the most glucose compared to any other organ in our body. While the brain accounts for roughly 2% of our body weight, it uses almost 20% of the sugars we eat or release from our body’s stores.

An increasing amount of research shows that people with AD and other forms of dementia experience insulin resistance in the CNS (central nervous system, which includes the brain and the spinal cord), similar to what people with type 2 diabetes experience in other areas of the body, such as the muscles, the liver, and the fat. Scientists have yet to determine exactly what the relationship between diabetes and AD or other forms of dementia may be caused by, but there are a few theories that have been proposed.

• One of these theories focuses on brain insulin resistance, which is when brain cells stop responding normally to insulin, leading to problems related to the ways our brain cells communicate, use energy, and fight infection. 

  • Insulin receptors can be found in many areas of the brain, where they are involved with brain cell growth, communication, and survival. While insulin levels are lower in the brain than in the bloodstream, all the insulin that makes its way to the brain comes from the same insulin produced in the pancreas – it crosses over what is known as the blood-brain barrier (or BBB). This barrier prevents unwanted things from the bloodstream from entering the brain. However, injected insulin does not cross the BBB. The reduced transport of insulin across the BBB may be why brain insulin levels are lower when the body experiences insulin resistance (such as in pre-diabetes and type 2 diabetes) and in diseases such as AD.

  • Insulin in the brain is known to help control our metabolism in certain other organs of the body, like the liver and fat tissue. The hypothalamus, the part of our brain that controls hunger, thirst, and emotions, is highly sensitive to levels of insulin in the brain. The association between type 2 diabetes and brain health may be due to problems with insulin’s actions in the hypothalamus, increasing a person’s likelihood of developing whole-body insulin resistance. 

• Diabetes also increases the risk for damaged blood vessels, leading to heart disease and stroke. Damaged blood vessels can starve the brain of oxygen, leading to cognitive decline and vascular dementia. 

• Diabetes disrupts how our bodies produce amylin, a hormone related to insulin that helps our bodies digest food. People with obesity and pre-diabetes often have high amounts of amylin, some of which can circulate and cross into the brain. Studies have shown that amylin can interact with the same protein deposits in the brain known to cause AD.

• Experiencing hyperglycemia for long periods of time can degrade the myelin sheath (a protective layer that surrounds your neurons). This leads to issues in how your nerves send and receive signals to your body. It can also lead to your brain cells dying.

Type 1 diabetes could be a risk factor for dementia for many of the same reasons as type 2 diabetes. In particular, the cardiovascular complications such as heart disease and stroke that are associated with type 1 diabetes could provide an explanation for its relationship with vascular dementia. Additionally, higher rates of cognitive dysfunction for those with type 1 diabetes could be related to frequent cases of hyperglycemia and hypoglycemia. Indeed, severe hypoglycemic and hypoglycemic events are associated with increased dementia risk for older adults with type 1 diabetes.

Is diabetes a risk factor for developing neurodegenerative disease? 

On average, people with diabetes experience slightly more cognitive difficulties associated with MCI across their lifespan, but experiencing cognitive difficulty does not mean you will eventually get diagnosed with dementia or AD. The prevalence of type 2 diabetes and neurodegenerative diseases, however, both increase with age, meaning it is more common for older people (65+ years) with type 2 diabetes to get diagnosed with vascular dementia or AD. 

Data suggests that people with diabetes have a 73% increase in the risk of developing any type of dementia and 56% increase in the risk of developing AD compared to people who do not have diabetes. This makes diabetes one of the strongest risk factors for getting dementia aside from aging. Health measures like A1C, cholesterol, high blood pressure(or hypertension), and eGFR are negatively impacted by diabetes and may also be associated with cognitive performance and neurodegenerative diseases.

• In the ACCORD-MIND trial, the largest and most rigorous study on diabetes and the brain to date, higher A1C levels were associated with lower cognitive function in people with diabetes. Similarly, another study found that the risk for dementia increased as a person’s A1C level increased, regardless of whether or not the person had type 2 diabetes. 

• A recent analysis of over 100 studies found that higher levels of LDL cholesterol (known as “bad cholesterol”) was an independent risk factor for the development of AD.

• High blood pressure in middle-aged people has been linked to future cognitive decline and dementia, and in particular, vascular dementia. This may be due to high blood pressure in the brain causing damage to blood vessels, such as small blockages and bleeding. 

• In a study on kidney health and dementia recently published recently, researchers found that lower rates of kidney filtration (as measured by eGFR) were associated with higher risk of onset of both vascular dementia and AD. 

What about Parkinson’s Disease?

Parkinson’s Disease (PD) is another neurodegenerative disease associated with aging. In PD, the cells in your brain deteriorate and begins to affect a person’s ability to perform daily activities associated with movement. Symptoms can include tremors (rhythmic shaking), muscle stiffness and rigidity, and PD can even slow your movement in a process called bradykinesia. It can also lead to other symptoms not associated with movement such as disrupting sleep, constipation, anxiety, depression, and fatigue.

As with other neurodegenerative diseases, research has been conducted to identify if there is a link between diabetes and PD. In particular, one study from 2018 showed an association between the two conditions. The researchers looked at the English National Hospital Episode Statistics and Mortality Data from 1999-2011 and divided the data into two cohorts, those with type 2 diabetes (2,017,115 people) at the time of hospital admission and those without (6,173,208 people). It was found that those with diabetes had a 30% higher chance of developing PD than those without, and the younger a person was with diagnosed type 2 diabetes, the more likely their chance of developing PD.

Though researchers do not yet understand the exact way that diabetes and PD are related, they do have a few hypotheses. Namely, there is the chance that certain genetic abnormalities that lead to diabetes may also lead to PD; even if one of these conditions does not directly cause the other, people who have one may be more likely to also have the other. In addition, when diabetes and PD coexist in a person, they may create a more hostile environment in the brain, leading the neurodegenerative processes underway in PD to speed up and be more severe.

What are strategies to reduce the risk of developing a neurodegenerative disease?

There is evidence that leading a healthy lifestyle can reduce your risk of developing diabetes-related complications like dementia or PD. For example, heart attacks and stroke can increase the risk of developing vascular dementia; therefore, lifestyle modifications that help you maintain an ideal blood pressure and levels of cholesterol for your age and health status are important. This can be accomplished by exercising regularly and consuming a diet low in saturated fat, salt, and sugar. 

Below are some other tips for improving brain health, which can go a long way in reducing the risk of neurodegenerative diseases like AD. The good news is that many of these strategies are also recommended for managing diabetes.

• Take control of your blood glucose levels by aiming for a greater time-in-range (TIR). To learn more about time-in-range goals, click here.

• Smoking is associated with higher rates of dementia. In a recent review, smokers were 40% more likely to develop AD than non-smokers. Given that people with diabetes are at an increased risk of developing dementia, smoking is likely to increase this risk further. If you smoke or experience nicotine addiction, talk to your healthcare professional about a plan to quit or cut back. 

• Keep blood pressure at the target discussed with your health care provider (which might be 130/80 mmHg or less, if you are at high risk of cardiovascular disease) by exercising regularly and eating a diet low in salt (aim for less than 2,300 mg of sodium each day)

• Take your diabetes medications consistently and as directed by your healthcare team. Some early evidence shows that certain diabetes drugs, like GLP-1 receptor agonists, may be beneficial for brain health. In fact, exenatide, a GLP-1 receptor agonist, is currently in clinical trials for treating PD.

• A very active area of research focuses on the dementia-preventing effects of having an active and stimulating mental life and rich social networks. Working to maintain an active and socially rich lifestyle could help prevent some of the effects of diabetes on dementia risk.

If you are 65 years of age or older and have memory concerns or other cognitive complaints (i.e., brain fog, depression, personality change), talk to your healthcare provider about getting a cognitive assessment. Learn more here.