Many of you in the baby boomer generation have already experienced this terrible scenario: A few years back, you noticed your aged mom or dad starting to forget things. Then it started to get worse. And then before you knew it, they were diagnosed with Alzheimer’s disease or dementia.
This is not an unusual occurrence. In the U.S. alone, there are more than 5 million people living with dementia and about 70% of those have Alzheimer’s disease. And these numbers are expected to increase.
But if you think Alzheimer’s disease (AD) is only something “old people” get, consider this. A recent report from the health insurer Blue Cross Blue Shield revealed that AD and early on-set dementia is surging among millennials.
That’s right. If you’re one of the older millennials and you think that AD is only something you have to worry about when you get older, then think again.
This observation from Blue Cross Blue Shield seems to correlate with a new study performed by researchers at Stony Brook University.
The researchers at Stony Brook found that communication among brain regions can begin destabilizing in individuals much earlier than scientists previously thought. Some individuals showed brain deterioration as early as their forties which worsened with age.
The importance of this is that as brain destabilization increases, cognition decreases.
The Stony Brook study also found that younger adults who had type 2 diabetes (T2D) exhibited brain network destabilization (i.e brain age) that was found in much older non-diabetics.
This finding was not novel. Many previous researchers have found that T2D and insulin resistance, a condition found in T2D, are highly associated with AD.
The bad news and the good news
Okay, there doesn’t seem to be a lot of good news here. Americans are getting dementia at younger ages. Our brains begin deteriorating at much younger ages than we thought. And if we have T2D or insulin resistance, our chances of getting dementia probably increase.
So what do we have to look forward to as we age? A progressive loss of cognition, possibly at a younger age with the possibility of something far worse such as AD.
Not necessarily! There’s a silver lining in this cloud.
The Stony Brook study also included a unique experiment that seems to confirm what other research has suggested. Dementia may be significantly tied to diet and how our brains use glucose for fuel.
This means that if we can adhere to some common sense dietary guidelines, we may be able to significantly reduce our chances of getting some form of dementia whether in early or later age.
Let’s take a look at the Blue Cross Blue Shield report and the Stony Brook study, and then see what we can do to improve our brain function and cognition throughout our adult life.
Alzheimer’s disease among millennials is surging
The major private health insurer Blue Cross Blue Shield reported that between 2013 – 2017, AD and early onset dementia increased 83% among commercially insured Americans aged 30 to 44.
In 2017 alone, about 131,000 commercially insured Americans between the ages of 30 and 64 were diagnosed with either condition.
Among these Americans, those between the ages of 30 to 64, early-onset diagnoses increased by 200%.
Individuals who were in the 45 to 54-year-old range experienced a 50% jump and those 55 to 64 experienced a 40% increase in diagnoses.
The average patient diagnosed with either AD or early-onset dementia was 49. Women were disproportionately more affected.
These statistics are nothing less than alarming and seem to be in line with other reports suggesting that early-onset AD is on the rise.
John Dwyer, president of the Global Alzheimer’s Platform Foundation, had this to say about the report,
Research has shown that Alzheimer’s disease starts in the brain years before clinical symptoms become apparent. This report shows that people as young as 30 have outward symptoms.
While the report alerted us to the increased incidence of dementia in younger adults, there were two important things the report didn’t tell us.
What about the APOE4 gene?
The first thing I would have liked to have known from this report was how many of those experiencing early-onset AD had the apolipoprotein E4 (APOE4) gene allele.
Okay, I realize the report was not a medical but a statistical report so I understand its exclusion. However, this is something important to be aware of concerning your risk of getting AD, no matter how old you are.
The APOE gene has three alleles or forms. They are APOE2, APOE3, and APOE4.
Each person receives one allele from each parent. If you have one copy of the APOE4 gene allele and one copy of the APOE3 allele (expressed as APOE3/APOE4), you have a 20-25% risk of developing mild cognitive impairment (MCI) or dementia due to AD by age 85.
If you have APOE4/APOE4 genotype, you have a 30-55% risk of developing MCI or dementia due to AD by age 85. There is also some evidence that individuals who have the APOE4/APOE4 genotype are at a greater risk for developing AD at an earlier age.
However, if you have the APOE4 allele, you don’t necessarily have to get AD.
Now, consider the risk for the other genotypes. The risk for the APOE3/APOE3 genotype is 10-15%, while the risk for someone possessing one copy of APOE2 alleles is less than this.
So, if you carry the APOE4 allele, your risk of developing AD dramatically increases.
The reason why I stressed this point is that researchers are now finding that the APOE allele may give us a clue on why some people develop AD at earlier ages. This may help healthcare individuals find ways to prevent and successfully treat the disease. More on that later.
Now to the other question I have about the Blue Cross Blue Shield report.
How many younger Americans getting dementia have T2D or insulin resistance?
And, as I mentioned before, insulin resistance is closely associated with type 2 diabetes and also obesity. And it’s also associated with dementia. More on that later.
Also, about 1 in 3 Americans have pre-diabetes. While this condition does not have the symptoms of type 2 diabetes, it is also characterized by insulin resistance.
So, we know that insulin resistance is closely associated with dementia, type 2 diabetes, and obesity, and these are all increasing among younger adults. Could this then be a possible reason why younger adults are experiencing increased rates of dementia?
It’s possible, but the report didn’t give us any stats to see if there was a correlation. Also, it would be exceedingly difficult to perform a clinical trial to find out.
Let’s look closer at the Stony Brook Study to see if we can strengthen the link between T2D, insulin resistance, and AD.
The Stony Brook University study on brain network stability
Neuroscientists believe that cognitive function results from interactions of various brain areas operating in large scale networks. Further, as the loss of functional communication between these networks decreases, poorer cognition results.
Lilianne R. Mujica-Parodi and fellow researchers at Stony Brook University used neuroimaging data from almost 1000 people, aged 18 to 88, and observed the stability of brain networks as individuals age.
The images showed that destabilization of brain networks progresses as we age and this can begin as young as 47-years-old with the most dramatic changes occurring at age 60.
The Stony Brook researchers were surprised to see this type of brain aging, as they called it, beginning at such an early age.
As I mentioned before, the researchers also found that young type 2 diabetics showed deterioration consistent with older non-diabetics.
So the Blue Cross Blue Shield report discovered that the number of younger adults who have dementia is rising. And Stony Brook showed that indeed brain aging can occur at younger ages than previously thought, especially among type 2 diabetics.
However, Mujica-Parodi and her colleagues didn’t end their study at just identifying how early brain network stability deterioration starts.
They wanted to see if they could discover the cause of the deterioration process and if something could be done about it. To do this, they added another component to the study.
The hypometabolism of glucose and network stability
The Stony Brook researchers had some clues as to what causes functional communication destabilization between brain regions.
Recently, several important studies have shown that AD and other types of dementia may have a metabolic origin — specifically the hypometabolism or underutilization of glucose by neuronal cells.
In this 2017 study, researchers observed positron emission tomography (PET) scans of individuals with dementia and Alzheimer’s and concluded that glucose hypometabolism was a reliable indicator for tracking the progression of cognitive decline.
An earlier study also involving PET scans revealed similar results. People at high risk for developing AD showed decreased rates of glucose metabolism in the brain decades before the appearance of AD symptoms.
What’s glucose hypometabolism got to do with AD?
Although the brain accounts for only about 2% of the body by weight, it requires about 20% of its energy intake. This energy mainly comes in the form of glucose.
In order to get that glucose into the cells of brain neurons, the hormone insulin must work efficiently.
However, in diseases like type 2 diabetes (T2D), metabolic syndrome, obesity, and even pre-diabetes, insulin doesn’t work properly.
Let’s take a quick look at insulin dysregulation as this will help us understand why glucose hypometabolism is so important in the development of AD.
T2D is a disease primarily characterized by hyperinsulinemia. That means that there is too much insulin being secreted by the pancreas.
There are several reasons why this happens. I believe the theory that has the most validity is that it is primarily caused by the constant overconsumption of refined carbohydrates including sugar.
These foods are ultimately broken down in your body into glucose. It’s insulin’s job to get the glucose (fuel) into your cells.
However, the more glucose that’s around (from eating too many refined carbohydrates), the more insulin will be secreted. If this happens for years, and insulin remains constantly high, there’s a good chance your cells will become resistant to the effects of insulin. That means your cells can’t get any more glucose into them.
(This is one reason why T2D is often discovered by high levels of glucose in the blood. Since insulin is having a hard time getting glucose into body tissues, it accumulates in the bloodstream.)
This is the result of hyperinsulinemia and ultimately insulin resistance.
What’s important though is that as the above process continues, the cells of your peripheral body organs such as the pancreas, liver, and even the brain can become resistant to the effects of insulin.
Insulin resistance in the brain
One of the effects of insulin resistance in the brain is the decreased availability of glucose to its neuronal cells.
Your brain needs a lot of energy in the form of glucose to function correctly. If it can’t get enough glucose, its structures and functions will break down. This will eventually result in cognitive decline. And the longer it goes on, the worse it becomes.
Type 2 diabetes is so closely linked with AD that AD is now commonly referred to as Type 3 Diabetes.
Further, a recent perspective in JAMA titled “In Alzheimer’s Research, Glucose Metabolism Moves to Center Stage” highlights the accumulating research suggesting glucose hypometabolism in the brain is not just a marker of Alzheimer’s disease (AD), but may perhaps be the cause of it.
So the Stony Brook researchers’ theory that the association of AD with glucose hypometabolism was supported by some solid research.
Stony Brook extends their study using ketones as a brain fuel
The researchers at Stony Brook understood the relationship between insulin resistance, glucose, and the brain, but they also knew that glucose is not the only fuel available to the brain.
The human brain can use ketones as an alternative fuel source.
Our bodies can access ketones in two ways. We can produce them endogenously in our liver from long-and medium-chain free fatty acids released from adipose tissue during fasting or when following a low-carbohydrate/moderate-protein/high-fat diet.
Or we can get them exogenously through supplementation with a d-β-hydroxybutyrate ketone ester.
The important thing is that ketones can fuel the brain without the need for insulin.
Relying on this concept, the researchers at Stony Brook devised a study to see if network stabilization increased when ketones were used as a primary fuel.
The Stony Brook ketone experiment
The Stony Brook experiment included 41 young (< 50 years old) healthy adults. Each individual was placed on a combination of different diets. They included a standard diet (primary fuel from glucose), a ketone producing diet, a high glucose diet, and a diet that included exogenous ketone.
MRI neuroscanning was used to measure brain stabilization.
Researchers found that brain activity increased and functional networks were stabilized by ketosis (the production of ketones), whether it was induced by a standard ketogenic diet, fasting, or exogenous ketones. All three interventions produced similar results.
The researchers were particularly surprised at how fast the brain responded to ketones. It was one week following a ketogenic diet and one hour after ingesting exogenous ketones.
The standard diet and high glucose diet produced a destabilizing effect on brain networks.
The significance of these findings is enormous for those at high risk for early brain aging, dementia, and AD.
If these conditions are related to a lack of fuel because of the hypometabolism of glucose, then adding an alternate fuel like ketones has a strong possibility of restoring the brain to a more youthful function.
The study did stress the fact that these were healthy young adults. It also suggested that more work has to be done in older populations.
Nonetheless, Mujica-Parodi explains the significance of their findings,
The bad news is that we see the first signs of brain aging much earlier than was previously thought. However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons.
The implications of the Stony Brook study
Mujica-Parodi and her colleagues showed that a ketogenic diet can restore energy to the brain and possibly produce a subsequent improvement in brain activity.
However, much more investigation must be done to see if ketones can have a direct effect on increasing cognitive performance in older populations.
But here’s the important point. Insulin resistance and the subsequent hypometabolism of glucose appears to be a large contributing factor in the development of dementia and AD, even in young adults.
And if insulin resistance can be detected early and treated, that could go a long way in preventing or mitigating the severity of dementia for many people, especially for those who are at a high risk.
Detecting insulin resistance
Most people find out they have insulin resistance when their doctor diagnoses them with type 2 diabetes. This usually happens when a blood test reveals that their fasting blood sugar or Hb1Ac test is high.
However, insulin resistance like AD and dementia can be present and progressing long before symptoms arise.
So, if you are significantly overweight or have a body type suggesting you have a lot of visceral fat (skinny-fat) and have a normal fasting blood glucose or Hb1Ac, you might want to ask your doctor about having your fasting insulin checked. See here.
Treating insulin resistance
As I’ve already stressed, a key to fighting AD appears to be overcoming the effect insulin resistance has on glucose metabolism in the brain.
The Stony Brook researchers showed that ketones as a brain fuel can be one way to do that.
However, what about individuals who have insulin resistance and don’t yet show outward symptoms of cognitive decline? Can insulin resistance be treated in order to prevent premature brain aging?
As I mentioned before, insulin resistance is closely related to T2D. The Mayo Clinic even suggests that it’s the cause of T2D.
Most doctors will treat T2D with insulin or some current diabetic drug. While these medications lower blood sugar to normal levels, they don’t really treat insulin resistance. They treat the effect insulin resistance produces
However, there is a treatment for insulin resistance. Very low carbohydrate diets can reverse insulin resistance. Also see here. Okay, that’s a lot harder than taking a pill. It means drastically reducing our consumption of refined carbs and sugar.
Unfortunately, we don’t know how much of an effect reducing or eliminating insulin resistance will have on reducing or preventing AD and dementia. Those experiments are extremely hard to perform. But we do know that it’s a large risk factor. And eliminating risk factors is always a good thing.
I want to add one other piece of research that appears to confirm that the Stony Brook researchers are on the right track when proposing that AD is mainly a problem of the hypometabolism of glucose.
Let’s take another look at the APOE allele.
The protective effect of the APOE2 allele
As I mentioned before, if you have one copy of the APOE4 allele, your chances of getting AD are increased. If you have two copies, your odds rise dramatically.
However, research has shown that the APOE2/APOE2 genotype is highly protective against AD.
This recent mouse study might shed light on the reason why.
Researchers discovered that mice carrying the APOE2 allele showed an increased uptake and metabolism of glucose in brain cells while the APOE4 brain displayed the most deficient profile.
Interestingly, the APOE2 and APOE4 brains showed a similar level of robust uptake and metabolism of ketone bodies.
Again, if the brain cannot metabolize glucose for energy, brain structures will deteriorate. There is recent evidence suggesting that decreased energy metabolism will damage synaptic function. Synapse damage is thought to be an early and progressive event in AD.
So, again, we see that there is evidence that the hypometabolism of glucose is associated with AD.
Okay, let’s summarize.
Alzheimer’s disease and dementia are occurring more frequently in younger adults. We don’t know exactly why. But we do know that Obesity and T2D are also increasing in younger populations and dementia is highly associated with these conditions.
Advanced brain aging associated with poorer cognition is now known to start in some individuals in their late forties. Research has shown that this process may be the result of the inability of people to metabolize glucose as fuel in their brains due to insulin resistance.
However, since our brain can use ketones as an alternative fuel supply, a very low carbohydrate diet that induces ketosis or the consumption of exogenous ketones has been shown to increase brain activity and network stabilization in healthy individuals.
Researchers at Stony Brook University speculate that if this can be done early enough in dementia, it might have the effect of returning the brain to a more youthful function.
Okay, that’s it for this post. If you have any comments, please let us know. Blessings and have a great week.
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