Alzheimer's Disease

The European Journal of Internal Medicine just published a paper discussing "Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet."  Authors Seneff, Wainwright, and Mascitelli provided this abstract:

"Alzheimer's disease is a devastating disease whose recent increase in incidence rates has broad implications for rising health care costs. Huge amounts of research money are currently being invested in seeking the underlying cause, with corresponding progress in understanding the disease progression. In this paper, we highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol, may lead to the development of Alzheimer's disease. A first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport. This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function. Over time, a cascade response leads to impaired glutamate signaling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis. Other neurodegenerative diseases share many properties with Alzheimer's disease, and may also be due in large part to this same underlying cause." [Emphasis added]

The idea certainly echos findings that type 2 diabetics (i.e. people with high blood sugar) have an increased risk of diabetes.  In search of an explanation for the link between diabetes and Alzheimer's, Salk Institute researchers did some experiments discussed in this article at Science Daily:

To get at the bottom of the question why diabetes predisposes people to Alzheimer's disease as they age, the Salk researchers Schubert, Burdo and Qi Chen, in collaboration with diabetes expert Nigel Calcutt, a professor in UCSD's Department of Pathology, induced diabetes in young mice, whose genetic background predisposes them to acquire the symptoms of Alzheimer's with old age.

These [high blood sugar] mice suffered damage to blood vessels well before any overt signs of Alzheimer's disease such as nerve cell death or the acquisition of amyloid deposits, the hallmark of the disease, could be detected in their brains. Further experiments revealed that the vascular damage was due to the overproduction of free radicals, resulting in oxidative damage to the cells lining the brain's blood vessels.

"While all people have a low level of amyloid circulating in their blood, in diabetics there may be a synergistic toxicity between the amyloid and high level of blood glucose that is leading to the problems with proper blood vessel formation," says Burdo. [Emphasis added]

 Some researchers have even proposed that Alzheimer's disease is a novel third form of diabetes:

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer's disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer's removes insulin receptors from nerve cells, rendering those neurons insulin resistant...

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer's disease, the Northwestern study sheds light on the emerging idea of Alzheimer's being a "type 3" diabetes.

Although some would love to blame the development of Alzheimer's disease on carbohydrates, I can't because we have data from Kitava contradicting it.

The Kitavans appear immune to Alzheimer's while consuming considerably more carbohydrate than the typical American.  Kitavan diets supply nearly 70% of calories as carbohydrate largely from various starchy roots (sweet potatoes, cassava, yam, taro), including a fairly large dose of fructose (perhaps as much as 36 g daily) from tropical fruits (bananas, guava, watermelon, pineapple).

The Kitavan experience provides evidence that they idea that carbohydrates cause Alzheimer's disease is simple hogwash. 

The fact is, diabetes is caused by high fat, high calorie diets, which cause cells to become insulin-resistant.  Yes, too much sugar in the blood promotes Alzheimer's, but elevated blood sugar is a disease of affluence, found only in nations which have high fat, high calorie diets.  It is rare to non-existent among people eating very high carbohydrate, very low fat diets, like the Kitavans, or the Tarahumara.   Hunter-gatherers and pastoralists eating presumably high-fat diets, such as the Inuit or Masai, are only protected by their low caloric intakes.

We have some evidence that vitamin D deficiency may promote Alzheimer's disease.  That study suggests that people with suboptimal D due to inadequate sun exposure have twice the risk of dementia compared to people with optimal D levels. Unfortunately, this study only shows a correlation between low D levels and Alzheimer's, which could be confounded by the so-called healthy subject effect.  That means that people who spend more time in the sun and get more vitamin D might also do something else--like eat less fat--that would protect them from dementia.

We also have evidence that stress promotes Alzheimer's disease:

Stress hormones appear to rapidly exacerbate the formation of brain lesions that are the hallmarks of Alzheimer’s disease, according to researchers at UC Irvine. The findings suggest that managing stress and reducing certain medications prescribed for the elderly could slow down the progression of this devastating disease.

The researchers injected four-month-old transgenic mice with levels of dexamethasone similar to the level of hormones that would be seen in humans under stress. At this young age, there would be little formation of plaques and tangles in the brains of the mice. After one week, the scientists found that the level of beta-amyloid in the brains of the animals compared to what is seen in the brains of untreated eight- to nine-month-old mice, demonstrating the profound consequence of glucocorticoid exposure. When dexamethasone was given to 13-month-old mice that already had some plaque and tangle pathology, the hormone again significantly worsened the plaque lesions in the brain and led to increased accumulation of the tau protein.

 Finally, to name a few explored by researchers, exposure to the following environmental neurotoxins (rare or absent in Kitava) might contribute to the development of Alzheimer's disease:

• organophosphate and organochloride pesticides (occupational exposure)
• lead exposure early in life
• mercury, primarily from dental amalgams (so-called "silver" fillings)

About the last item, although having a large number of amalgam fillings appears to increase the risk of Alzheimer's, I do have to comment that having a large number of amalgam fillings would also be a marker for consumption of a refined food diet, so it could be that both the fillings and the dementia are caused by diet.

Some people believe that a meat-based, low-carb diet may prevent or reverse Alzheimer's. Gasior, Rogawski, and Hartman reviewed the evidence here, stating:

Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury.

In a murine model of Alzheimer's disease, Van der Auwera et al showed that a short-term, high saturated fat, ketogenic diet reduced deposits of toxic amyloid-ß plaque by 25%.  However, they also found that "Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures."  In other words, it didn't modify the disease, which suggests that the ketogenic diet is not beneficial for this disease and further that the plaque may not be the cause of the disease.