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The Link between Diabetes and Alzheimer’s Disease

on March 26, 2018

by Chris Kresser

The incidence of Alzheimer’s disease in the United States has risen exponentially over the past two decades. A growing body of research indicates that Alzheimer’s is closely linked to diabetes and suggests that the correction of blood sugar dysregulation may represent a crucial step in the prevention and treatment of this devastating disease. Read on to learn about the link between Alzheimer’s disease and diabetes and how you can help your patients protect their brain health through diet and lifestyle strategies that improve blood sugar control and insulin sensitivity.


Alzheimer’s disease is a multifactorial illness

Alzheimer’s disease (AD) is a devastating condition that robs individuals of their memory, mental function, and independence while also taking a massive emotional toll on family members and caregivers. In an effort to stem the rapidly rising tide of Alzheimer’s disease, the conventional medical paradigm has poured billions of dollars into funding for neurodegenerative disease research. However, this massive expenditure has proved unfruitful; Alzheimer’s disease clinical trials demonstrate an extremely bleak 99 percent failure rate. (1) The dramatic failure of Alzheimer’s clinical trials is due to the medical community’s approach to research, which is primarily focused on developing a “miracle drug” for AD and fails to take into account the multitude of factors that contribute to this complex chronic illness.

Dr. Dale Bredesen, an internationally recognized expert on neurodegenerative disease, argues that a Functional Medicine approach, rather than monotherapy, is the best strategy for addressing Alzheimer’s disease. In fact, in his practice, he has shown that it is possible to not only prevent but cure Alzheimer’s disease with such an approach. You can learn more about Dr. Bredesen’s approach in my podcast interview with him and this blog post. Over the course of his many years of experience working with AD patients, he has identified several AD “types,” each of which is caused by a unique combination of dietary, environmental, and lifestyle triggers.

  • Type 1 (“inflammatory”): Caused by pathogens or other inflammatory factors such as dietary trans fats.
  • Type 2 (“atrophic”): Caused by a lack of factors that support brain health such as BDNF, estradiol, vitamin D, and other nutrients.
  • Type 3 (“toxic”): Caused by exposure to mycotoxins or chemotoxins.
  • Type 4 (“vascular”): Caused by reduced blood flow to the brain.
  • Type 5 (“traumatic”): Caused by trauma to the brain.

Last but not least, Dr. Bredesen has identified AD Type 1.5, which he refers to as “glycotoxic” Alzheimer’s disease. This type combines inflammation from high blood glucose levels with a trophic loss of insulin sensitivity. A growing body of research demonstrates that blood sugar dysregulation is intrinsically linked to neurodegeneration, thus supporting Dr. Bredesen’s concept of glycotoxic Alzheimer’s disease.

New research links Alzheimer’s to diabetes, and correcting blood sugar dysregulation is a crucial step in the prevention and treatment of this devastating disease

Prediabetes and diabetes have officially reached epidemic proportions in the United States. A shocking 21 million Americans have diabetes, and 54 million have prediabetes, a condition in which blood sugar levels are higher than normal but not yet diabetic. If left untreated, prediabetes typically morphs into diabetes within 10 years of diagnosis. The incidence of Alzheimer’s disease is also on the rise. Approximately 5.5 million Americans are living with the disease, and this number is expected to grow as the proportion of the U.S. population 65 years and older continues to increase.

At first glance, diabetes and Alzheimer’s appear to be two distinct diseases. However, a growing body of evidence indicates that diabetes and Alzheimer’s disease (AD) are linked because both conditions involve impaired glucose homeostasis and altered brain function.

Several lines of evidence support the association between diabetes and Alzheimer’s disease:

  • Diabetics demonstrate distinct cognitive deficits, including decreased execution and processing speed, impaired verbal and nonverbal memory, and atrophy of the hippocampus and amygdala, which also occurs in Alzheimer’s disease. These patterns are foretelling of future cognitive dysfunction and neurodegeneration. (2, 3, 4)
  • Hyperinsulinemia, a feature of prediabetes, is associated with a decline in memory and an increased risk of AD. (5)
  • Elevated body mass index, a hallmark of diabetes, is a risk factor for amyloid-beta deposition in the brain; amyloid-beta plaques are misfolded protein structures that promote cell death and tissue loss in the Alzheimer’s brain. (6)
  • An elevated two-hour glucose measurement after an oral glucose tolerance test is associated with an increased risk of Alzheimer’s disease. (7)

Clearly, there is a relationship between features of diabetes and Alzheimer’s disease. What mechanisms are responsible for this relationship? Research suggests that hyperglycemia and insulin resistance in the brain may be the common thread linking these two conditions.

Blood sugar dysregulation harms brain function

The blood–brain barrier, a “filtering” system of cells that restricts the passage of substances from the bloodstream into the brain, is highly permeable to insulin. In fact, insulin receptors are present in all cell types in the brain, including neurons, microglia, and astrocytes. This means that insulin produced by the pancreas and released into the circulation can travel directly to the brain and influence its function. Indeed, insulin plays many vital roles in the brain: it mediates neuronal growth and metabolism, neurotransmission, and synaptic plasticity; promotes neuronal survival by inhibiting apoptosis; and regulates cognition and memory. (8)

Prediabetes and diabetes are characterized by insulin resistance, a condition in which body tissues are unresponsive to insulin and cannot move sugar efficiently into cells to fuel normal metabolic processes. Insulin resistance is typically caused by sustained high blood sugar concentrations, which cause a continuous release of insulin by the pancreas to lower blood sugar. Over time, high blood sugar and insulin concentrations promote desensitization of insulin receptors to insulin. While insulin resistance is typically observed in muscle, hepatic, and adipose tissue, emerging research indicates that sustained high blood glucose levels also cause insulin resistance in brain tissue.

Insulin resistance harms the brain by impairing neuronal function, altering levels of catecholamine neurotransmitters, and promoting neuroinflammation. These adverse effects may contribute to the hallmark symptoms of Alzheimer’s disease: impaired memory and ability to learn, reduced ability to make judgments and communicate, and changes in personality and behavior such as anxiety, agitation, and delusions.

The scientific community’s newfound understanding of the relationship between blood sugar dysregulation and Alzheimer’s disease has encouraged research efforts to discover interventions that may alleviate brain insulin resistance and protect brain health. Excitingly, the research indicates that dietary and lifestyle interventions are effective strategies for optimizing glycemic control, promoting brain health, and preventing neurodegeneration.

Optimize glycemic control to protect brain health

A Functional Medicine approach that addresses diet, physical activity, and gut health can help optimize glycemic control and prevent the adverse cognitive changes and increased risk of Alzheimer’s disease associated with diabetes.

Diet

A Westernized diet high in processed, refined foods and carbohydrates has been found to promote brain oxidative stress and metabolic disturbances characteristic of diabetes. (9) This finding is not altogether surprising, given the inflammatory, diabetogenic nature of the Western/Standard American Diet (SAD). Getting patients off of the SAD and onto a whole-foods, nutrient-dense diet thus represents a crucial step in Alzheimer’s disease prevention and treatment. A Paleo diet is an excellent place to start because it has therapeutic benefits in the treatment of diabetes and may, therefore, alleviate the elevated blood glucose and insulin resistance that underlie glycotoxic Alzheimer’s disease. (10)

The nutrient-dense Paleo diet also provides the body with vitamins, minerals, and fatty acids that promote healthy brain function and prevent neurodegeneration.

  • Vitamin A: Inhibits the formation of amyloid-beta plaques. (11) Found in egg yolks, liver, and cod liver oil.
  • Vitamin D: Influences blood sugar regulation and may improve cognitive outcomes in Alzheimer’s disease. (12) While sun exposure is the primary source of vitamin D, the vitamin is also found in cod liver oil, sardines, salmon, mackerel, tuna, eggs, and raw milk.
  • Vitamin C: Inhibits the formation of amyloid-beta plaques and reduces brain oxidative stress. Found in a variety of fruits and vegetables including broccoli, brussels sprouts, citrus fruits, peppers, and kiwi. (13, 14)
  • Vitamin E: Inhibits oxidative stress and scavenges free radicals in the brain. (15, 16) Found in almonds, spinach, avocado, olive oil, and sweet potatoes.
  • B vitamins: B vitamins, including folate, B6, and B12, inhibit oxidative stress and lower homocysteine, which has been associated with an increased risk of AD. (17) Dark leafy greens, broccoli, citrus fruits, and avocado are good sources of folate; beef liver and other organ meats, tuna, summer squash, and bananas are high in B6. Vitamin B12 is found in animal foods such as red meat, poultry, eggs, and dairy.
  • Selenium: AD subjects demonstrate a deficiency of selenium, which is a crucial antioxidant and may play a role in antioxidant defenses in the brain. (18, 19) Selenium can be found in seafood, poultry, nuts, seeds, and eggs.
  • Omega-3 fatty acids: DHA, an omega-3 fatty acid, reduces amyloid-beta production and affects the expression of genes involved in the inflammatory Alzheimer’s disease process. (20) A higher intake of fish, which is rich in omega-3 fatty acids, is also associated with a reduced risk of memory decline. (21)

Finally, strategically modifying carbohydrate intake via a ketogenic diet may also be beneficial for Alzheimer’s disease patients. A ketogenic diet restricts carbohydrate intake to between 20 and 50 grams per day, causing the body to rely on ketones for energy production rather than glucose. Research indicates that the ketogenic diet reduces glucose and insulin in the brain, lowers neuroinflammation, and improves cognitive function in AD subjects. (22)

Physical activity

Sedentary behavior adversely affects glycemic control in the brain and increases the risk of cognitive decline. (23) Engaging in moderate-intensity physical activity promotes healthier patterns of glucose metabolism in the brain and represents a useful strategy for preventing glycotoxic Alzheimer’s disease. (24)

Gut microbiome

Finally, preliminary research suggests that both diabetics and Alzheimer’s disease patients have altered gut microbiomes compared to healthy controls. (25, 26) The altered gut microbiota may promote insulin resistance, thus influencing the course of these diseases. While more research is needed, these findings suggest that taking steps to create a healthy gut microbiome may be a useful preventive measure for AD.

Now I’d like to hear from you. Have you observed any associations between diabetes and Alzheimer’s disease in your practice? Would you recommend dietary and lifestyle strategies that optimize glucose control to your patients with Alzheimer’s disease? Let me know in the comments below.

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