According to Dr Dale Bredesen, cognitive decline is largely due to 3 fundamental threats to our brain: inflammation, a shortage of cognition-supporting molecules and toxic exposure. Alzheimer’s disease is a protective response to these three brain threats. Inflammation and a shortage of cognition -supporting molecules are linked to metabolism. Metabolism is a function of our diet, level of activity, genes and our handling of stress, so conditions such as pre-diabetes or Insulin resistance, obesity, vitamin D deficiency and sedentary lifestyle increase our risk.

1- Prevent and reduce inflammation:

Inflammation is our body’s response to attack by infectious agents such as Borrelia (Lyme disease) or non-infectious stress such as sugar-damaged proteins or trans fats.

We are constantly exposed to potential invaders from bacteria, viruses, fungi and parasites. If the threat is chronic and the inflammatory response is continuously activated it causes problems. One of the ways the body responds to invading pathogens is by producing amyloid, the substance that forms the brain plaques that characterize Alzheimer’s. In the brain of someone who died from Alzheimer’s, pathogens could be found: bacteria from the mouth, molds from the nose, viruses such as Herpes from the lips, Borrelia from a tick bite.

More scientific evidence concluded that after the brain is invaded by pathogens, it produces amyloid to protect the synapses and brain cells but when amyloid production is overboard it kills the synapses and brain cells.

Inflammation can also arise without infection. It is triggered when we eat trans fats in fast food or sugar. Inflammation can occur in “leaky gut” often from consuming gluten or dairy or grains. The gut lining develops microscopic holes allowing fragments of food or bacteria into our blood stream triggering chronic inflammation.

When the inflammation is caused by sugar toxicity, it is associated with insulin resistance. The glucose molecules attach to many proteins, inhibiting their functioning. Our body responds to the flood of sugar by increasing the production of insulin, which reduces glucose by pushing it into the cells. But with the chronically high level of insulin, the cells become resistant to the effects of insulin.

Glucose attaches to many different proteins, Haemoglobin A1C is one of many such molecules. These hitchhiking glucose molecules undergo biochemical reactions to produce advanced glycation end products (AGE). Since the proteins with AGE look different to our immune system, antibodies can develop against them triggering inflammation. The AGE bind to their own receptors called RAGE which also triggers inflammation. The AGE cause free radicals and these unstable reactive molecules damage anything they bump into such as DNA and cell membranes. Insulin level should be below 4.5 and HbA1C less than 5.6 %.

Insulin is intimately related to Alzheimer’s. After insulin molecules lower the glucose, the body must degrade the insulin in order to prevent dropping the blood glucose too low by the action of insulin-degrading enzyme (IDE). IDE also degrades the amyloid but the enzyme can’t do both at once. If IDE is breaking down insulin, it can’t break down amyloid therefore chronically high levels of insulin increase the risk of Alzheimer’s.

High levels of Homocysteine are important contributors to Alzheimer’s. Alzheimer’s results when the synapse-making signals in the brain are outweighed by the synapse -remodeling /destroying ones. Homocysteine is a marker of inflammation but is also increased when nutritional support is suboptimal. Keeping the homocysteine low requires active form of Vitamin B6, B12 and folate. Goal B12=500-1500pg/ml, folate=10-25ng/ml, B6=60-100mcg/l.

lnflammatory markers: C Reactive protein CRP goal <0.9mg/dl, ratio of albumin to globulin >1.8, ratio of omega 6 to omega3 in red blood cells >0.5 and <3, Interleukin 6<3pg/ml, tumor necrosis factor alpha <6.0pg/ml.

2- Optimize cognition- supporting molecules like hormones, nutrients.

At the annual meeting of the Society for Neuroscience, scientists found that people who died in their 90s and who retained excellent memories still have brains riddled with amyloid plaques. There are 2 leading hypotheses. One is that if people are well educated and intellectually engaged throughout life, they may have enough redundant synapses to withstand the loss of some to the amyloid plaques (high cognitive reserve). Other alternative is there are biochemical mechanism to fight amyloid or to strengthen synapses enough to withstand the amyloid assault.

Brain-derived neurotrophic factors (BDNF) strengthen synapses. BNDF can be increased by exercise, hormones such as estradiol and testosterone and nutrients such as vitamin D and folate. When the brain runs low on BNDF, it responds by producing amyloid.

Reduced Vitamin D3 is associated with cognitive decline. Vitamin D travels through the blood and tissues and when enter the cells will bind to vitamin D receptor allowing the vitamin D to enter the nucleus and turn on over 900 genes. Some affect bone metabolism, others suppress tumour formation, others reduce inflammation and others are crucial for creating and maintaining brain synapses.

3- Eliminate toxins. heavy metals

When the brain is infiltrated by toxic chemicals such as copper and mercury or by biotoxins as mycotoxins from molds, amyloid binds up to these toxins to keep them from damaging neurons.

Too much copper and too little zinc are associated with dementia. Taking proton pump inhibitor may cause low zinc due to poor absorption from low acid in stomach. Copper produces free radicals.

Magnesium is critical for brain function. In Alzheimer’s there is a good chance that the memory consolidating structures ( hippocampi) are low in magnesium. Taking Magnesium threonate improves cognition.

Selenium and glutathione: low levels of glutathione can contribute to inflammation, toxicity, and loss of support for synapses. Selenium plays a key role in re-generating glutathione when it is used up scavenging free radicals, so a reduction in selenium have been shown to be associated with cognitive decline.

Mercury, arsenic, lead and cadmium can also affect brain function.

4- Sleep and sleep apnea

Sleep affects cognition through multiple fundamental mechanisms.

It alters the cellular anatomy of the brain allowing a cleansing. The space in between brain cells (the extracellular space) expands during sleep allowing more calcium and magnesium ions to flow through. This is thought to flush out cellular debris including amyloid.

Sleep is also associated with a reduced formation of amyloid.

We don’t eat when we sleep. Fasting improves insulin sensitivity.

During sleep, our brain cells activate autophagy, “self eating” to recycle cellular components like damaged mitochondria and misfolded proteins, improving cellular health. Without autophagy, our cells would collect dysfunctional components.

Sleep is also a time of repair. Growth hormones increase during sleep, repairing cells and new supportive brain cells are produced during sleep.

Sleep deprivation impairs cognition. Moreover, it increases the risk of obesity, diabetes and cardiovascular disease, all risks factors of Alzheimer’s. It gives us cravings for sugar, unhealthy fats to give us an Alzheimer’s inducing metabolic profile.

Sleep apnea is an important contributor to cognitive decline.

5- Cholesterol and other lipids.

We are all worry about high cholesterol. Aerobic exercise is better than measuring cholesterol. This is because many people with high cholesterol have no problem with vascular disease and many with normal cholesterol have significant vascular disease.

Perhaps surprisingly, low rather than high cholesterol is associated with cognitive decline, brain atrophy. Cholesterol is a key part of cell membranes including those of brain cells.

6- Vitamin E, vitamin B1

Vitamin E is an important protector of cell membranes, an anti-oxidant with anti-Alzheimer’s effect. Goal Vit E Alpha-tocopherol= 12-20mcg/ml.

Vitamin B1- thiamine- is critical for memory formation. Thiamine deficiency is associated with alcohol abuse and malnutrition causes memory loss called Wernicke-Korsakoff syndrome. Whether thiamine plays a role in the cognitive decline associated with Alzheimer’s disease or aging is less clear.

7- Gastrointestinal permeability “Leaky gut”

When the gut lining is leaky, as can occur due to gluten sensitivity, chemicals, bacteria food can enter the blood stream triggering inflammation. Our immune system responds, sometimes in a way that causes lateral damage to our own tissues because, to the immune cells, they resemble the invaders. The result is autoimmune condition with persistent low level of inflammation and in the worst case, cause autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or lupus erythematosus. The chronic inflammation can also contribute to Alzheimer’s. There are several ways to detect gut permeability. We can test by ingesting mannitol and lactulose, mannitol passes through the gut barrier normally whereas lactulose doesn’t unless the gut is leaky. They can be measured in the urine.

8- Blood brain barrier permeability.

A growing list of diseases causing by bacteria, viruses, fungi were found in brains of patients with Alzheimer’s such as bacteria from the mouth, nose, herpes simplex, Borrelia (Lyme disease). Fungi, neurosyphilis. Microbes can access to the brain through the nose, through the vagus nerve connecting the gut to the brainstem



Reference:

The End of Alzheimer’s by Dr Dale Bredesen

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