Nobody wants to develop Alzheimer’s disease, Parkinson’s disease, dementia, or any other brain degenerative disease as we grow older. Of course, you want to grow older, but you want to grow older with good brain function. If there is something you can do to prevent these from happening, would you do them? And there are many actions you can do.

The incidence of Alzheimer’s disease (AD) has increased remarkably over the last 40-50 years. Since 1970, there has been a remarkable 92% increase in the incidence of AD in the USA. The costs have gone up too, and in 2010 a RAND corporation study showed the cost of taking care of dementia patients was $159 to $215 billion.[1] Compare this with the cost of care for Heart disease at $102 billion and for cancer $77 billion and you can see we spend 2-3 times more on dementia than these other serious conditions.

In order to prevent a disease, you have to know why you get the disease. Most dementias, including AD and Parkinson’s disease, start off with some insult that results in activation of certain cells within the brain, called microglia, to produce an immune response to fix or take care of that insult. These cells secrete inflammatory cytokines to do this, which are like poisons to the insult. As they fight the insult, the inflammatory process that occurs produces byproducts of destruction including free radicals. These are free electrons which can injure other tissues if not kept contained, which produces oxidative stress.

Oxidative stress especially injures certain parts of our cells called mitochondria. These are the power houses of our body and are present in all of our cells, including our brain cells (neurons). Once damaged, they fail to produce energy for the cells which can result in cell death, and in the brain this could be neuronal death. In AD patients, this neuronal death takes place primarily in those neurons that work by secreting a neurotransmitter called acetylcholine. This results in a decrease in acetylcholine in the brain and poor brain function.

Most traditional treatments for AD today focus on increasing the amount of acetylcholine in the brain with the use of inhibitors of the destruction of this neurotransmitters, called cholinesterase inhibitors. One of the most commonly used ones is called Aricept. The problem is they treat the end problem. What we really need to do is focus on preventing the process from happening at the beginning of this cascade, for once you get AD, there’s not much you can do about it.

First we should focus on actions you can do that will decrease the damage to the mitochondria by decreasing the oxidative stresses to them. After all, the mitochondria are powering the neurons to transmit electrical impulses which results in good brain function. They use the oxygen we breathe in to do this, a process called oxidative phosphorylation.

Mitochondria have their own type of DNA within them that controls their function. The power within them is produced by another chain reaction called electron transport: the oxygen combines with a compound called ADP and from ATP, which produces the energy source for the cell. This is the oxidative phosphorylation reaction.

In Alzheimer’s, studies have shown there is a defect in this electron transport chain reaction throughout the entire brain.[2] Indeed, without healthy mitochondria, the cell has no more energy and dies, called apoptosis. [3] When the mitochondria become so affected, it is said that they undergo a process called oxidative stress.

Oxidative stress to the mitochondrial DNA is thought to be a cause of neuronal impairment which can result in AD or Parkinson’s disease. We have known this for years. In fact, in the 70s, an illicit street drug, called MPTP, and some pesticides, rotenone and maneb, were found to induce Parkinson’s disease within a few days of taking it. They did so by damaging the electron transport system in mitochondria. [4] Thus, oxidative stress destroys the normal process of oxidative phosphorylation.

Once oxidative stress occurs, it self-worsens. By damaging the mitochondria, this results in release of more byproducts called ROS (Reactive Oxygen Species). With more ROS you get more damage, more damage results in more ROS, and a vicious cycle is formed that doesn’t need to happen if we prevent it from starting from the beginning.3

To date, there are no drugs out there available that increase the health of mitochondria. However, there are non-pharmaceutical actions you can take. The top two are dietary restriction and exercise. [5] In other words, reducing the amount of food you eat and exercising regularly can help you prevent AD from forming. In case you haven’t figured this out yet, these also help you lose weight too.

Anything you can do to protect your mitochondria and improve their function will not only give you better health, but will also decrease your risk of developing dementia diseases. Improving the amount of oxygen to your tissues and ultimately to the mitochondria is a good start. Thus, improving circulation, i.e. exercise, stopping smoking, is a good start. Improving your pulmonary function through the right exercise is another one. Increasing oxygen to the tissues increases the formation of ATP within your mitochondria through improved oxidative phosphorylation.

Exercise also induces the growth of new cells in your brain. [6] Exercise has been shown to improve mental function in adults. One study showed an improvement in cognitive function after just 24 weeks of exercise averaging 142 minutes of exercise per week. [7] The large Nurses’ Health Study also concluded that exercising resulted in less cognitive decline by 20%. [8] But doing stretch exercises isn’t enough; you must do aerobics to decrease your risk.

Some supplements will also help. Taking CoQ10 is the first step. CoQ10 is necessary for oxidative phosphorylation to occur. High doses of CoQ10 have been shown to treat AD [9] and Parkinson’s disease.[10] Mitochondrial dysfunctions have also been treated with high doses of glutathione (up to 600 mg daily IV) with good results. Glutathione is a potent antioxidant but is poorly absorbed. However, we can take N-acetyl cysteine orally and it is converted into glutathione in the body to help give you this support.

Another action we can do is from the study of epigenetics, the control of our genes or DNA. The DNA in our cells are static, they don’t change. But, there are “switches” that affect our DNA that can turn parts of our genes on or off. There are many compounds that we can ingest that can turn on our genes to help us live longer and improve our health.

One particular nutrient is omega 3 fatty acid, particularly DHA. DHA improves brain function by turning on the gene that stimulates the production of brain cells. It improves regeneration of neurons and reduces oxidative stress damage to them. [11] A very large prospective study, the Framingham Heart Study, showed a decrease in dementia when DHA was elevated in the blood-up to a 47% reduced risk of developing dementia of all causes.[12] Another action of DHA is as an anti-inflammatory agent. [13]

Inflammation of brain cells contributes to development of neurological diseases. In fact, the degree of inflammation correlates with the severity of dementia the person has. [14]Inflammation causes oxidative stress which causes mitochondrial dysfunction.

Oxidative stress damage to tissues is an early event in the formation of Alzheimer’s disease. [15]

If we can identify this problem is happening, perhaps we can prevent the progress or perhaps even the onset of the disease. There are two things we can measure that gives us an idea of the amount of oxidative stress you have in your body. One is HgbA1C, which measures the amount of glycation in your body.

HemoglobinA1c (HgbA1c) is a test we use to measure how a person with Type 2 diabetes is doing on therapy. In DM, insulin resistance is increased the Chianti study. [16]

Another method to determine the amount of oxidative stress in your body is to measure the level of lipid peroxides in your serum or urine (TBARS).[17] A prediabetic state, called the IRS (Insulin Resistance Syndrome) occurs early in development of type 2 diabetes. Here, blood sugar levels are consistently high after eating, forcing the body to produce extra insulin to metabolize the sugar. However, it overloads the cells and they thus become resistant to the effects of the insulin, or what we call insulin resistance. Thus, in the IR Syndrome one sees high fasting insulin levels (>2) and elevated hemoglobin A1c (>5.6).

Unfortunately, when the IRS develops, it is a risk factor for cognitive decline. In a study by Geroldi in the Arch of Neurology in 2005, older participants in the study were evaluated. If they had IRS, their risk for cognitive decline was almost 3 times more than normal participants, and 4.3 times more if they require insulin to control their blood glucose.

Hemoglobin A1C is a measure of the amount of red blood cells that have sugar molecules attached to their protein. It is an example of an Advanced Glycosylation End Produce, or what we call AGEs. The more AGEs you have, the more cognitive decline is seen. In a study by Yaff in Neurology, 2011, 920 elderly people were evaluated for cognitive impairment over 9 years. [18] Those with diabetes had much lower cognitive scores than those without diabetes.

Interestingly, HgbA1c levels also correlate with another protein in our body LDL. You may remember LDL as the “bad” cholesterol that increases heart disease. However, it is not LDL per se that is bad, it is when the LDL becomes glycated LDL that causes the problem of plaque formation in the arteries, increasing the risk of plaque formation over 6 x higher. [19]Since the two correlate, if one has high levels of HgbA1c and elevated LDL, then their glycated LDL is most likely elevated also. Treatment of both is thus similar in both cases.[20]

AGEs exert adverse biological effects on tissues partly by increasing inflammation in the tissues. They activate the intracellular signal that leads to increased synthesis of cytokines, a hallmark for presence of inflammation, and an increase in free radical production resulting in an increase in oxidative stress and mitochondrial failure. [21] Glycated proteins produce 50 times more free radicals than non-glycated ones. [22]

Thus, you can reduce inflammation and reduce oxidative stress by reducing their glucose levels in your blood. To reduce your blood glucose levels, you need to eat a low carb diet filled with foods that have a low glycemic index <50 and a low glycemic load of <20. Reducing inflammation is key to slowing down the aging process. Fruits are okay too since their glucose is mixed with fiber, but concentrate on those with low glycemic indexes.

So how do you measure AGEs? Simply do a Hemoglobin A1C (Hgb A1C) blood test, easily done at our doctor’s office. Hgb A1C is an AGEs and is a good measure of the level of glucose in your body over the last three months. Interestingly, it is also a good measurement of brain shrinkage. As the HgbA1c increases over 5.2, the brain progressively shrinks too. [23] Thus, if you have an elevated HgbA1c > 5.2, you should consider losing weight if overweight, and changing your diet to low carbs to eliminate as much sugar from your diet as possible.

Even fasting blood glucose levels above 90 showed progressive cognitive decline over time. [24] In a recent study in the NEJM, if the fasting blood glucose rises to 115, the incidence of dementia increases incrementally.[25] Their conclusion was that higher glucose levels are associated with an increased risk of dementia.

In Alzheimer’s disease, there is deposition of a protein, called amyloid, on the neurons. It was thought that this protein per se caused the sluggishness seen in Alzheimer’s patient. However, when given meds to reduce the amyloid, the patients’ dementia worsened. The problem is not the amyloid protein, the problem is when this amyloid becomes glycated with sugar molecules, i.e. become an AGEs. When this happens, it starts the inflammation cascade with production of cytokines from the microglia which results in free radical formation and oxidative stress.

Further, oxidative damage is an early event in the development of Alzheimer’s disease. We can therefore slow the progress of or prevent the onset of this disease by reducing this oxidative damage.[26] As you recall, formation of AGEs causes release of inflammatory cytokines resulting in inflammation which causes much of this oxidative stress. Preventing the formation of AGEs thus may be the best first step in preventing AD, along with decreasing inflammation and oxidative stress.

The conclusion would be to reduce AGEs as much as possible to prevent this cascade from occurring. There are quite a few compounds that can decrease AGEs. They include Alpha-lipoic acid, resveratrol, N-acetyl cysteine, DHA, benfotiamine, taurine, carnosine and aspirin. A low carbohydrate diet also decrease AGEs, which is probably the most important nutritional therapy one can do to decrease AGEs in their body.

Lifestyle interventions is probably the best therapy to prevent Alzheimer’s disease. Giving drugs may help, like Metformin. But doing regular exercise and eating a low carb diet is necessary and provides the best result to decrease AGEs. [27]

 

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[2] NEUROLOGY 1994;44. 1060-1064
[3] International Journal of Alzheimer’s Disease, Volume 2009, Article ID 951548
[4] AJNR 16:61-68 Jan 1995
[5] Pharmaceuticals 2009, 2; 150-167
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[12] Schaefer, E., et al., Archives of Neurology 63; 1545-1550; November, 2006
[13] Youdim, K., et al., International Journal of Developmental Neuroscience: 383-399; July 1, 2000
[14] Ho,L., et al., Arch Neurol 58;487-492; March, 2001
[15] Markesbery, W., Arch Neurol. 2007;64(7):954-956; July, 2007
[16] Geroldi, C.,  et al., Arch Neurol 62; July, 2005; 1067-72.
[17] Tamoaka, A., te al., Neurology 54: 2319-2321; June, 2000
[18] K. Yaffe, MD, et al., Neurology, October 4, 2011, 77:1351-56
[19] Diabetes, Vol. 60, February 2011
[20] Eur.JClinChemClinBiochem. Vol 31; 1993; pp 707-713
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[22] Durany, N., et al., European Archives of Psychiatry and Clinical Neuroscience 249(3); S68-S73; December, 1999
[23] Enzinger, C., et al, neurology 64: 1704-11; May 24, 2005
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[25] NEJM, 369;6  August 8, 2013
[26] Markesbery, W., Arch Neurol. 64(7): 954-956; July, 2007
[27] N Engl J Med. Vol. 346, No.6, February 7, 2002