One of the most significant challenges in the world is discovering the cause of Alzheimer’s disease. The primary symptom of Alzheimer’s is a progressive mental decline that causes memory loss. People forget their own families and even lose the sense of self. Alzheimer’s disease, which mostly affects the elderly, is projected to increase in the future because the population continues to get older.

Importantly, chronic inflammation impacts Alzheimer’s disease (AD). Various research “studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis (1).” In addition, there are multiple reports non-steroidal anti-inflammatory drugs (NSAIDs) may have some preventative effects on this disease (2) (3) (4). Inflammation associates with increased microglia response, as discussed in Chapter 8. Given this information, it is no surprise research found “increased proliferation of microglial cells in human Alzheimer’s disease (5).”

As previously discussed, inefficient mitochondria produce more reactive oxygen species, which creates resistance to insulin and higher blood glucose levels. This increase in blood glucose happens because cells do not want to raise glucose metabolism when mitochondria are already struggling with damage caused by too many reactive oxygen species. This pattern of effects, when severe, causes type II diabetes.

Amazingly, research found that brain insulin resistance and “its consequences can readily account for most of the structural and functional abnormalities in AD (6).” Also, other researchers note that “glucose abnormality plays a critical role in AD pathophysiological alterations through the induction of multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, and so forth (7).”

As discussed in Chapter 6, excessive glucose metabolism damages the mitochondria. Too much glucose in the blood also increases inflammation. Therefore, eating too many refined carbohydrates can create excessive inflammation that damages the brain. Over a long time, this damage accumulates to the point that brain damage is much more noticeable.

Given this information, it is unsurprising research found “a dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk” of mild cognitive impairment or dementia in the elderly (8). Furthermore, Alzheimer’s involves such major glucose-related problems that some researchers think of Alzheimer’s as type 3 diabetes (9). In line with this idea, type 2 diabetes is “a significant risk factor for developing Alzheimer’s disease later in life (10).”

If high glucose intake increases the risk of brain damage, then limiting refined carbohydrate intake may improve brain health. Research found a ketogenic diet, which is low in carbohydrates, improved the Alzheimer’s Disease Assessment Scale-cognitive subscale score (11).

However, as mentioned, the ketogenic diet often does not have many important phytochemicals. Also, unless this diet is well-planned, the ketogenic diet does not provide enough micronutrients needed for long-term health.

A different type of diet that has more phytochemicals and micronutrients is the Mediterranean-Dash Intervention for Neurodegenerative Delay diet, known as the MIND diet. A study found an association between this diet and a significantly lower risk of Alzheimer’s disease (12). The phytochemicals and antioxidants in many of the foods in the MIND diet may reduce the inflammation and damage from glucose that is the primary cause of this disease.

A risk factor for Alzheimer’s disease is having the apoe4 lipoprotein. There are variations of this lipoprotein. Most people have apoe3. Fewer people have apoe4 lipoprotein, and even fewer have apoe2. Apoe4 is important because this lipoprotein version increases insulin resistance. In contrast, apoe3 does not cause as much resistance.

Interestingly, the apoe4 variation has a south-to-north gradient in Europe, “with the proportion of e4 carriers from only 10-15% in the south to 40-50% in the north (13).” In addition, apoe4 is more common in foraging communities, while more apoe3 variation exists in areas that have an agricultural economy (14).

Historically, both foragers and people in more northern climates had less consistent access to foods with a lot of carbohydrates. The apoe4 variation is an adaption that allows the eventual transformation of more glucose into fat for storage on the body. This increased storage as fat allowed people with limited glucose access to eat more carbohydrates when these foods were suddenly available. For example, during the fruiting of trees, apoe4 carriers could eat and store more of the fruit energy than apoe3 carriers. Evolutionarily, the apoe4 variation helped those people survive during limited food supply.

However, now high glucose foods are constantly available in modern society. Because of this, the ancient advantage of apoe4 is now a disadvantage. As mentioned, there is an association between more fat in the blood and insulin resistance, which is a reason authorities promoted a diet low in fat.

However, the actual problem is the combination of high fat with high glycemic load foods. This combination is an issue because glucose and fat are in competition to be metabolized by the mitochondria. A diet high in fat is not a problem if avoiding high glycemic load foods. In contrast, eating a lot of saturated fat with high glycemic load foods increases the amount of glucose in the bloodstream. This causes many health problems.

Apoe4 increases insulin resistance by causing more fat to remain in the blood, which limits the normal function of insulin. Although the metabolism of glucose creates more reactive oxygen species than fat metabolism, a frequently high blood glucose level also causes a lot of inflammation and damaging health effects. One of these health effects is glial cells releasing various inflammatory molecules. The glucose damage and higher inflammation combine to destroy many neurons. This is the reason apoe4 affects Alzheimer’s disease risk.

As a side note, the design of the brain is to metabolize glucose, ketones, and lactate because most fatty acids are unable to cross the blood-brain-barrier. However, the rest of the body is not designed to mainly metabolize glucose. Excess glucose metabolism throughout the body creates excess reactive oxygen species and diminishes antioxidant defenses. This impairs the brain’s ability to manage its own reactive oxygen species, creating damaged mitochondria.

As previously discussed, damaged mitochondria increase insulin resistance. Because of this insulin resistance, too much glucose accumulates in the brain’s blood. Over the long-term this causes too much inflammation in the brain and the destruction of many neurons.

If the issue in Alzheimer’s disease is too much glucose, then cancer, which rapidly removes glucose from blood, might reduce the risk of Alzheimer’s disease. Amazingly, researchers found the risk of developing dementia of the Alzheimer type is less among people that have a history of cancer (15). Glucose and its effect on inflammation is the main connection between these two health conditions.

For the previously mentioned reasons, stopping refined carbohydrate consumption and improving mitochondria function using the many ideas in this book may benefit Alzheimer’s and decrease the risk of getting the disease. Also, consuming a lot of fresh vegetables and fruits with their many phytochemicals is helpful. In addition, make sure to regularly fulfill all nutrient requirements.

Improvements may also happen by participating in many cognitively simulating activities. Research found “frequent participation in cognitively stimulating activities is associated with reduced risk” of Alzheimer’s disease (16).

Interestingly, other research using a mouse model found a 40 Hertz light flickering regime reduced amyloid-beta and affected genes associated with the transformation of microglia (17). However, the best way to drastically reduce the risk of Alzheimer’s disease may be to use the many different ideas in this book that reduce inflammation and improve overall quality of life.