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A growing body of scientific evidence suggests that people with type 2 diabetes have an increased risk of developing Alzheimer's disease. Convincing animal data and preliminary research in patients with early cognitive decline have shown positive outcomes using strategies to overcome insulin resistance. In this clip, Dr. Peter Attia explains his position on the relationship between insulin resistance and Alzheimer’s disease risk.
Rhonda: Yeah. So what are your thoughts as to what are triggering Alzheimer's disease in terms of our environment?
Peter: Yeah. I mean, I think it's probably a combination of things. But the most compelling evidence to me and, again, this is probably, because I'm just a simpleton and I like to start with Occam's razor, is it's very hard to dispute the high association between Alzheimer's disease and Type 2 diabetes and hyperinsulinemia. And so I'm in the camp of which some neurobiologists are, but not all. This is still far from being settled. I sort of view Alzheimer's disease as brain diabetes, and I think if the ApoE genotype as basically just a susceptibility.
So I think anybody can get Alzheimer's disease with any genotype if there's enough insulin resistance, if there's basically enough difficulty in getting glucose through pyruvate dehydrogenase and into the Krebs cycle. So I think it's a neuronal energy problem more...and I think all of the other things we see are results of that. But in terms of what the driver is, I think it's a neuronal energy problem. And I think all of the tau plaque, the neuronal, the synapse stuff, I think those are byproducts.
And I think in animal models there's some very convincing data that you can...you know, I mean you've seen the stuff I'm sure more than I have, right? Simultaneous injection of glucose and insulin can transiently overcome deficit, administration of exogenous BHB can overcome the deficit by bypassing and going straight through alpha-hydroxybutyrate into the Krebs cycle. So where you can reverse the signs and symptoms.
Now, I'm not particularly in this space though I find it really interesting. There's a guy by the name of, Richard Isaacson. Do you know Richard? He's a neurologist at Cornell and he has a practice that focuses on early cognitive decline that utilizes very-low-glycemic-index diets coupled with MCT and stuff. So it's basically like inducing ketosis without a full-on ketogenic diet, which obviously for many people is challenging. And he's seen very promising results. I think he's running a couple of clinical trials as well.
And there's a whole sort of...I don't know what the word to describe it is. But there's a whole network of people out there with all of their interesting data that are, because we don't have controls, we just don't know if this is, like, a performance bias we're seeing or if there's a true impact. But anyway that's sort of my hypothesis, which is I don't actually know what's causing Alzheimer's disease, I don't know how to treat it, I don't know if it's treatable once it's in a late enough stage, but I firmly believe that if you can be as insulin-sensitive as possible, for you as an individual you reduce your risk.
Now, that doesn't mean that the risk ever goes to zero for any of us, regardless of ApoE genotype, but I know that if I have to choose between being very-insulin-sensitive and not-so-insulin-sensitive I'm going to be better off in this camp. And I think that's frankly true for every disease state.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
One of three common genetic variants of the APOE (apolipoprotein E) gene. The APOE4 allele, which is present in approximately 10-15% of people, increases the risk of developing Alzheimer's disease and lowers the age of onset. Having one copy of E4 increases risk 2- to 3-fold, while having two copies increases risk as much as 15-fold.
A chemical produced in the liver via the breakdown of fatty acids. Beta-hydroxybutyrate is a type of ketone body. It can be used to produce energy inside the mitochondria and acts as a signaling molecule that alters gene expression by inhibiting a class of enzymes known as histone deacetylases.
The genetic constitution of an individual organism. The combination of genotype and environment determine an organism's physical characteristics – known as the phenotype.
A value (between 0 and 100) assigned to a defined amount of a carbohydrate-containing food based on how much the food increases a person’s blood glucose level within two hours of eating, compared to eating an equivalent amount of pure glucose. Glucose has a glycemic index value of 100. Whereas eating high glycemic index foods induces a sharp increase in blood glucose levels that declines rapidly, eating low glycemic index foods generally results in a lower blood glucose concentration that declines gradually.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
A physiological condition in which cells fail to respond to the normal functions of the hormone insulin. During insulin resistance, the pancreas produces insulin, but the cells in the body become resistant to its actions and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.
A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.
A series of enzymatic reactions that aerobic organisms use to produce energy. Also known as the citric acid cycle or the tricarboxylic acid cycle, the Krebs cycle takes place in the mitochondria. It comprises eight reactions and eight intermediates that break down carbohydrates, fats, and proteins into adenosine triphosphate (ATP) and carbon dioxide. It also produces the precursors of certain amino acids and the reduced form of nicotinamide adenine dinucleotide (NADH), a cofactor for many biological reactions.
A class of saturated fats. Medium-chain triglycerides are composed of medium-length fatty acid chains (six to 12 carbons long) bound by a glycerol backbone. They occur naturally in coconut oil, palm oil, and butter, but they can also be synthesized in a laboratory or food processing setting. Evidence suggests that MCT therapy improves cognitive function in older adults with Alzheimer's disease.[1] Examples of MCTs include caprylic acid (C8), capric acid (C10), and lauric acid (C12).
One of the enzymes involved in the process of converting pyruvate, which is derived from glucose, into energy in the form of ATP inside of the mitochondria.
The junction between one neuron and another or a gland or muscle cell. Synapses are critical elements in the transmission of nerve signals. Their formation is necessary for the establishment and maintenance of the brain’s neuronal network and the precision of its circuitry.
A microtubule-bound protein that forms the neurofibrillary "tau tangles" associated with Alzheimer's disease. Tau tangles disrupt transport of metabolites, lipids, and mitochondria across a neuron to the synapse where neurotransmission occurs. Diminished slow-wave sleep is associated with higher levels of tau in the brain. Elevated tau is a sign of Alzheimer's disease and has been linked to cognitive decline.
A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.
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