Sugar and its Role in Dementia

Avoid Getting Stupiderer.

BY: DR. BAYNE FRENCH MD DC

Tell Me Something I Care About:

• Regular consumption of sugar reduces brain size, which correlates with being less smart.
• Medical treatments for cognitive decline and dementia are lacking. Maintaining a healthy brain and cognitive abilities is all about prevention through being metabolically well. 
• I feel that disallowing sugar from being a dietary staple, and not using it for an exercise fuel, is one of the most powerful choices one can make for their brain health.

The Burden of Dementia:

Dementia is defined as a progressive loss of cognitive abilities affecting memory, judgment, reasoning and thinking that interferes with daily functioning. It has a few causes, with Alzheimer’s being the most common.

It is increasing in incidence.  In 2019 there were 57.4 million cases of dementia. It is expected to increase to 152.8 million cases in 2050 (Lancet Public Health, 2019). It currently affects about 10% of individuals over the age of 65. 

The primary form of dementia is Alzheimer’s disease..
Dr. Alois Alzheimer was a German psychiatrist. I wonder why the Germans always figure this stuff out. Grandstanders.
Anyway, Dr. Alzheimer was a lousy croquet player, and allegedly afraid of the dark. One day he was bored, and started cutting on the brain of a dead woman who had clearly lost her marbles. Not that psychiatrists go anywhere near scalpels nowadays. He noted that her brain had widespread entangled web-like material, later identified as beta-amyloid. This is a deformed protein that then triggers the formation of another bad actor call Tau. Until recently, the accumulation of these abnormal proteins was considered the cause of Alzheimer’s disease.  

Research on Sugar:

Sugar consumption has firmly been linked with cardiovascular disease, being metabolically unwell, and also as a driver of systemic inflammation (Huang et al. BMJ. 2023; Huang et al. Nutrition. 2023; Semnani-Azad et al. JAMA. 2020; Ma et al. Front Immunol. 2022). ALL of these problems affect the brain over time. Numerous other studies have ascertained an association specifically between sugar-sweetened beverages and obesity, diabetes, heart disease and stroke (Malik et al. Circulation. 2010; Nutrients. 2019).

A study published in 2023 also reported on sugar-sweetened beverage consumption and and increase in dementia risk (Chen et al. Am J Clin Nutr. 2023). The Zhang et al. study discussed in depth later takes this much further, examining a huge group of sugar-eating people over several years and explored the underlying mechanisms of how sugar makes us dumber and more incapable.

The massive Framingham Heart Study found that the highest consumers of sugar had the smallest brains and worst memory (Pase et al. Alzheiners Dement. 2017). And don’t think that being a woman, and all smart and stuff, with your fancy estrogen, makes you special. You’re not. A study from the gigantic Women Health Initiative (Liu et al. Nutr Neurosci. 2022) determined that higher sugar consumption was associated with a higher Alzheimer’s risk in women. In fact, Alzheimer’s disease is twice as common in women.

The MMSE (Mini-Mental Status Exam) is a relatively brief and standardized tool to screen for an individual patient's cognitive abilities.  The best score possible is 30 out of 30.  I scored a 47. 24 or greater is considered normal. Below that is evidence of cognitive decline of some type. Chong et al. (Clin Interv Aging. 2019) ran MMSE's on over 1200 patients. They found that the higher the sugar, the lower the MMSE scores.  As sugar goes up, smartness goes down. I think that’s called an inverse relationship, but I’ve never been good at relationships.

Liu et al. (J Affect Disord. 2022) and Sun et al. (J Prev Alzheimers Dis. 2022) are two more studies that look specifically at how drinking sugary crap on the regular affect’s cognitive abilities.  It was unfavorable, meaning people that drank sugar-sweetened beverages lost their intelligence. Zhang et al. in the large study listed below states "all these investigations together validated the robustness of the finding that sugar intake is tightly correlated with dementia".

Agarwal et al. (J Alzheimers Dis. 2023) followed almost 800 patients for over 7 years. Those individuals with the highest sugar consumption were twice as likely to develop dementia, compared to those with the lowest sugar consumption. The average sugar intake was 106 grams per day. I consider this crazy high. I ate this much between 2003 and 2005 after the birth of my first child, Highland, when I was working on my dad bod.

As a side note, many sugar addicted endurance athletic pontiffs recommend consuming about this much per hour of exercise, which is the topic of a recent article I wrote, High Carbohydrate Athletic Fueling. A Fad Metabolic Dumpster Fire. The response to this article by some dogmatic sugar-addicts was, well, not sugar-coated.
As a side-side note, these are the same individuals that fully admit high sugar consumption is bad for health, but that exercise somehow makes you immune to its toxicity. That’s like saying ionizing radiation won’t affect your DNA as long as you’re doing pushups during exposure. Or how about this one…the bad effects of drinking a sugary soda are offset by then drinking an artificially flavored one. Who ARE these people?

Can we continue with the work of Agarwal et al. please? Stop going off on tangents. Agarwal and associates determined that for every 10% increase in calories from sugar, dementia risk increased by 40%. 

Again, the usual suspects of sucrose, especially fructose, were associated with the highest dementia risk. The highest consumers of this sugary crap developed dementia on an average of 7.1 years earlier than those that consumed the less.

In regards specifically to fructose, those that consumed the most of it had a 2.8 times higher risk of dementia. Described more below, half of sugar (sucrose) is fructose, and high-fructose corn syrup has even more fructose.

Interestingly, the sugar maltose (comprised of two units of glucose) was NOT associated with an increase in Alzheimer’s risk in Agarwal’s work. This is a very important finding, as choices in sweets or an endurance fuel comprised of longer chains of glucose, seem to be metabolically more favorable.

Sugar Refresher:

Many things are called sugar, but true sugar is sucrose, a disaccharide, meaning it is composed of two monosaccharide molecules.  Those molecules are glucose and fructose. Each is absorbed readily from the small intestine into the bloodstream and exert widespread and powerful metabolic actions.

Excess glucose results in a spike in blood sugar, with a resultant spike in insulin. Insulin is directly contributory to atherosclerosis and also to the formation of cancer. It also directly suppresses burning fat for fuel. Instead, insulin drives fat formation through a process called lipogenesis. Chronically elevated insulin over time leads to insulin resistance and the human mammal maladies of weight gain, fatty liver disease, prediabetes, type 2 diabetes, and heaps of time in doctors’ offices.

Fructose is even worse. It is naturally occurring, primarily in fruit. It’s relative amount in fruit is low, and its potential detrimental effects are muted by fruit fiber and a host of phytonutrients. Fructose from sugar and high fructose corn syrup consumed regularly is just brutal to contend with.  It drives Fatty Liver Disease and the formation of uric acid.

210,832:

Zhang et al published a study in BMC Medicine in 2024. The potential relationship between dietary sugar intake and dementia was studied in a large-scale population, over 210,000. 

They evaluated sugar consumption in different ways.  Increased absolute sugar intake  (grams/day) was significantly associated with all causes of dementia, and specifically Alzheimer's disease.  Relative sugar intake is a similar but different way of looking at sugar intake as a percentage of total caloric consumption for the day.  Higher relative sugar intake also demonstrated significant associations with all dementias.

Patients in this study were broken up into 4 groups (quartiles) depending on how much sugary crap they ate and drank. Q1 consumed the least and Q4 consumed the highest.  The average age of study participants was 56 years with 45% being male, and 55% female.  Be reassured that the investigators made sure that they did not compete against each other.

Over about 12 years, 1877 developed dementia with 781 being specifically diagnosed with Alzheimer's disease.  Multiple sources of sugar consumption were evaluated but "sucrose was most robustly associated with all-cause dementia and Alzheimer's disease".  And the highest sugar consuming quartile had the highest incidence of dementia.

The authors felt that this was the first study to investigate a pattern between high sugar consumption and dementia in a large-scale population.  Show-offs. They state: “Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia". Dr. Yudkin in his book Pure, White, and Deadly also thought so, back in 1972. I was two years old then, and distinctly remember reading Dr. Yudkin’s book between diaper changes.

They continue: “we first provided evidence that high adherence to the high sugar dietary pattern was an important modifiable risk factor for dementia, especially all cause dementia, and the general population".                                                             
Let’s be honest, it isn’t difficult to have “high adherence” to a high-sugar diet. Sugary crap tastes good, influential people, including athletes, recommend it, and if you don’t care much about cardiovascular disease, cancers and getting dumber then I say bottoms up!

Biochemical Geekout:

A patient that says “just tell me what to do”, makes me uneasy. They intend to rotely do what I suggest without any knowledge as to why.
Observationally over time, the durability of their lifestyle changes is lacking. They just do not continue with what they intended. It’s the same with diets.
I have found that a basic explanation of what is happening chemically in their body in response to a dietary habit is impactful.  This however takes time and does not lend itself to an efficient day in clinic.  It’s much easier to just plug an individual into a population metric, and send in an Rx. Our medical system is just not set up for wellness. You are responsible for that.

Elevated blood sugars are directly toxic to tissue.  For the brain and other nerve tissue, glucose is "neurotoxic".  Through a variety of mechanisms metabolism directly is distorted.  This further damages nerves and blood vessels.  Arterial disease, directly driven by regular sugar consumption, is widely known to damage to the brain. Discussed later, this may represent a primary cause of dementia.

There are also several oxidative stress reactions at play.  I have written on oxidation previously in an article titled What Oxidation Means for You, which was snubbed for a Pulitzer.
Brain-derived neurotrophic factor (BDNF) is a chemical secreted by brain tissue that helps protect brain cells (neurons) and also serves a role in learning and memory.
An interesting study on mice (Molteni et al. Neuroscience. 2002) showed that these cute little reptiles that ate a lot of sugar had a lot less BDNF.  These mice simply could not learn as well as their non-sugar addicted buddies and couldn’t remember the names of their littermates. 

A hallmark of the most common cause of dementia, Alzheimer's disease, is the accumulation of beta-amyloid in the brain.  This is what Dr. Alzheimer observed. Beta-amyloid is a large protein that forms in plaques in the brain of Alzheimer’s patients. Whether beta-amyloid is a cause or an effect of the disease remains unclear.  Elevated consumption of sugar leading to insulin resistance has been directly linked with beta-amyloid accumulation in the brain (Kellar et al. Lancet Neurol. 2020; Willette et al. Alzheimers Dement. 2015), bringing into question that maybe being metabolically unwell increases dementia risk.

A bit more on insulin resistance. It’s a pandemic metabolic condition almost completely driven by excessive carbohydrate (especially sugar) consumption. In this scenario, blood sugars have been elevated repeatedly over time, leading to large amounts of insulin release from the pancreas. The bodies tissues get sick of being flogged by insulin and develop a resistance to it. This then leads to a massive burden of disease. Several studies have suggested that insulin resistance plays a role in becoming dumber (Arvanitakis et al. Ann Neurol. 2020; Talbot et al. J Clin Invest. 2012; Kullman et al. Physio Rev. 2016).

Specifically, higher insulin levels alter a glucose transporter in the brain called GLUT4, causing it to down regulate. This directly impairs memory (Pearson-Leary et al. Behav Brain Res. 2018).

Stay With Me:

Grizzanti et al. (JCI Insight. 2023) first of all is a cool name. I would love to have “Griz” in my name. Grizzly bears and I have history, as several of their brethren have attempted to dismember me, my ability to irritate you all is only made possible by bear spray.

Anyway, this cool-named dude and his colleagues at Wake Forest University (go Hooziers!) reported on a channel, on the surface of nerve cells, called KATP, that regulates energy for that nerve cell.
They also reported in mice that increased sugar consumption, leading to elevated blood glucose, triggered the accumulation of beta-amyloid in the brain. 

 But how? Beta-amyloid is a toxic protein. The authors wanted to find out how elevated blood sugar led to the formation of this nasty compound. They removed the KATP channel from mice and found that high blood sugar then did NOT result in beta-amyloid formation.

Why am I telling you this? Because I want you to understand that there are identifiable cellular mechanisms whereby habitual sugar consumption and the resultant metabolic caldron directly results in toxicity to the brain. And I also want those that find me “unscientific” to shush it.

A Bit More About Mice:

Carvalho et al. (Diabetes. 2012) studied these cute little amphibians. Mice were divided into 3 groups: 1) normal mice eating normal mouse food; 2) normal mice eating lots of sugar; and 3) genetically altered mice making them highly susceptible to dementia, that also ate lots of sugar.

The researchers picked sucrose as the poison of choice because of “compelling evidence showing that excessive consumption of sugar plays a key role in the epidemic of obesity and T2D (type 2 diabetes)”.

The sugar consuming mice weighed more, yet had smaller brains. They also had higher levels of blood sugar, insulin, and fat levels in their blood. These findings are absolutely consistent with what I see all day long in human mammal regular sugar consumers, including athletes.

There was another fascinating tidbit found in the study involved mitochondria.      Within each cell of mice and men resides mitochondria. This is where energy (ATP) is made. There can be hundreds or even thousands of mitochondria inside each cell.
The mitochondrial transmembrane potential is fundamental for efficient ATP production. The sugar-eating mice had an impairment here, and could generate less ATP. This is further evidence of how sugar is antithetic to optimal human (and mice) performance. Refer to an earlier article I wrote Sugar. The Antithetic Performance Enhancer for more on how sugar chemically makes us less physically capable.

In this study, the mice did their thing for 7 months. Some drinking lots of sugar and some not. They were then killed by decapitation. This sounds gruesome and would’ve probably been more humane to just cut their heads off.
Anyway, their brains were then studied. The researchers asked to use my electron microscope but my kid was looking at boogers with it.   

The mice genetically engineered for high Alzheimer’s susceptibility, who also ate lots of sugar, had the highest amounts of beta-amyloid in their brains under electron microscopy. But normal mice, that also ate lots of sugar, also had high levels of beta-amyloid.
The healthiest brains were from the mice that did not eat sugar. Instead, they drank water and ate regular mouse chow, which I find dry and flavorless.   

Don’t Forget Poop: 

Crosstalk between the gut and the brain fascinates me. Lots of things fascinate me. For instance, it’s fascinating that all I see of elk in hunting season is their butt-end as they run away from me.
Oh, and the concept mentioned earlier is that if you exercise really hard, sugar is allegedly not toxic. I find that fascinatingly lacking of any merit.

I plan on doing a much larger article on how a healthy gut and microbiome confers a healthy metabolism, but for now, know that Kawano et al. (Cell. 2022) discussed how high-sugar consumption distorts our normal gut bacterial flora. This then contributes to oxidative stress, unhealthy metabolism, neuro-inflammation and other “hallmarks of Alzheimer’s disease” through a disrupted microbiota-gut-brain axis.

Makes you want to drink some sugary crap before your next run, doesn’t it? That’s hyperbole for those of you fortunate enough to not be familiar with my writing style.

Emerging Concepts:

You now know that the abnormal protein beta-amyloid is seen in the brains of patients with Alzheimer's disease.  Historically, treatment research has targeted this protein, assuming it is the causal influence.  There is growing data however that this protein may be a result of the disease, its production triggered by abnormal metabolism and cardiovascular disease in the brain itself. Arteries in the brain can be visualized and the amount of calcium within them measured. Bos et al. (Alzheimers Dement. 2015), and many other researchers report how arterial disease in the brain correlates with a higher incidence of dementia.

“Vascular dementia" is a form of dementia caused by arterial occlusion and strokes.  It has traditionally been considered completely distinct from Alzheimer's disease.  Newer thinking however really blurs these lines.  It seems highly probable that minimizing cardiovascular risk factors will also greatly reduce the risk of developing dementia.

What are We to do?

With a lot of disease states, there’s exists many treatment options. For America’s biggest killer, cardiovascular disease, there are numerous very good medications, and also procedures like stents and coronary artery bypass grafting.
Similarly, there are numerous treatment options for diseases like obesity, diabetes, and cancers.

This is not true for dementias. It’s all about risk reduction, prevention, with nutrition at its core.

Like with most disease, there are genetic propensities. Specifically, with Alzheimer’s, there are ApoE gene mutations that confer a heightened (sometimes dramatically) risk of developing this disease. Lifestyle and especially diet have strong influences on our genome however, termed epigenetics.

The more I read, research, and observe, the more it seems absolutely critical that prevention and metabolic wellness represent our best defense in preserving our mental faculties. Like most things involving health, wellness, and proper human mammal nutrition, asking your medical provider will likely be futile. Most providers do not understand wellness and if they did, they simply cannot take the time to explain it competently.

With good cardiac (heart) fitness, collateral circulation to heart muscle develops. The benefit being that if a major vessel becomes occluded (heart attack), less of a catastrophe may ensue if that downstream muscle also gets blood from other non-occluded routes.

A similar concept may apply to the brain. More complex neurologic networks develop over time with concerted “training”. Performing more varied and complex cognitive tasks can create a brain more resistant to decline. I’m not saying you need to speak eight foreign languages fluently like I do, but it’s never too late to make your brain work.

It is not uncommon for individuals to report that they fear dementia more than any other condition, including death.  When people (you hopefully) realize that dementia may be viewed not as a genetically-dictated inevitability with advancing age, but as a metabolic disease, a plan may then take shape to reduce risk. This is hopeful. This puts meaning behind action.

Here’s a list of action items to protect your brain:

1. Disallow sugar from being a staple and never fuel with it for exercise. Reserve it for occasional intake, in small amounts, for a celebratory event, and never on an empty stomach.
2. Exercise. There are many studies that show significant reductions in dementia incidence in those that regularly exercise. Wanigatunga et al. (JAMDA. 2025) showed that there was a dose-response relationship between exercise and dementia, even in the very old and frail. For every 30 minutes of exercise above 126 minutes per week, there was an additional 4% reduction in all types of dementia.
   It appears that a combination of cardio and resistance exercise is the best. Grip strength can be easily measured with a hand-held dynamometer, and serves as a surrogate measure of total body strength. Estaban-Cornejo et al. (J Cachexia Sarcopenia Muscle. 2022) reported that lower grip strength correlated with a higher risk of all-cause dementia.
3. Reduce all forms of carbohydrate.
4. Intermittent fasting. There is a plethora of metabolic benefits with this practice. With fasting, fat is burned. When fat is burned, people tend to lean out, which confers dramatic health benefits over time.
   Also with fat burning, ketones are produced. These provide an excellent source of brain fuel. With advancing age and cardiovascular disease, the brain does not burn glucose as well, which may underlie the causality of dementia more than anything else. Thus, providing a “blend” of brain fuel makes a lot of sense to me.
   
5. Stress management. Ennis et al. (Neurology. 2017) measured the amounts of the stress hormone cortisol in the urine of almost 2000 patients for over 10 years. More dementia was seen in those with higher cortisol levels. If you figure out how to reduce stress effectively, I beg you to let me know.
6. Sleep. Like being in good physical shape, sleep should be absolutely prioritized. Smart people at Harvard looked at 2,600 patients over years and published their findings in Aging in 2021. Those that slept under 5 hours per night were twice as likely to develop dementia compared to those that slept 6-8 hours.

I feel that dementia, like cancer, Fatty Liver Disease, obesity, and type 2 diabetes is largely a metabolic disease. Focusing on that which will allow you an efficient metabolism will thereby reduce your risk of dementia, a devastating condition for which there are no effective treatments. 

Understanding the toxic role that sugar plays on the brain is an excellent place to start. As always, rely only on yourself to make the best decisions about your health. Inquire, read, think, observe, and learn. Your brain depends on it.