CHAPTER 8

G IS FOR GENETICS

GENES ONLY LOAD THE GUN; YOUR BEHAVIOR PULLS THE TRIGGER

I lavish unfailing love to a thousand generations. I forgive iniquity, rebellion, and sin. But I do not excuse the guilty. I lay the sins of the parents upon their children and grandchildren; the entire family is affected —even children in the third and fourth generations.

EXODUS 34:7

BUD: LEARNING TO MITIGATE THE GENETIC FACTOR

Bud, 52, came to see me because he was concerned about his memory, focus, and energy. His mother had died of Alzheimer’s disease, and he had a wife 20 years his junior and two young children, ages five and seven. From his history, I learned he had untreated ADHD and bouts of depression that were becoming more frequent as stress piled up at work. He also had one copy of the APOE e4 gene variant; mild hypertension; prediabetes; high CRP, ferritin, and LDL cholesterol; low vitamin D, DHEA, and testosterone levels; untreated sleep apnea; and erectile dysfunction. In addition, Bud carried an extra 30 pounds, putting him in the obese category. His BrainFit WebNeuro showed significant memory, attention, and executive problems. His SPECT scan showed decreased activity in the frontal and temporal lobes. Bud was clearly headed for serious trouble. He had multiple risk factors that were damaging his brain, his fortune, and his family.

BUD’S “BEFORE” BRAIN SPECT SCAN

Surface SPECT scan showing areas of very low blood flow.

BUD’S BRIGHT MINDS RISK FACTORS AND INTERVENTIONS

BRIGHT MINDS

BUD’S RISK FACTORS

INTERVENTIONS

Blood Flow

Low blood flow on SPECT, hypertension, high LDL cholesterol, erectile dysfunction

Exercise, ginkgo biloba

Retirement/Aging

Age 52, high ferritin (iron)

Blood donation to lower ferritin, antioxidant-rich diet

Inflammation

High CRP

Diet, omega-3 fatty acids EPA and DHA

Genetics

Family history of Alzheimer’s, APOE e4 positive

  

Head Trauma

    

Toxins

    

Mental Health

Chronic stress, ADHD, mild depression

Stress management tools, ADHD treatment

Immunity/Infection Issues

Low vitamin D

Vitamin D3 supplements

Neurohormone Deficiencies

Low DHEA and testosterone

Exercise, weight lifting, limited sugar, DHEA supplements

Diabesity

Prediabetes and obesity

Memory Rescue Diet

Sleep Issues

Sleep apnea

CPAP machine

After seeing his scan and test results, Bud was determined to become an active participant in his health. He radically changed his diet by cutting out his usual six daily sodas, severely restricting his sugar intake, increasing the protein and healthy fat in his diet, and reducing grains and processed carbohydrates. He started weight lifting twice a week and replaced his typical once-or-twice-weekly slow walks (30 minutes apiece) with burst training three times a week (see page 73 for more on this type of exercise). He started wearing his CPAP machine to treat his sleep apnea and was faithful with his supplement regimen.

Over the next year, Bud lost 30 pounds, and his blood sugar and blood pressure dropped to normal levels without any medication. He reported that his memory, focus, and energy were better than they had been in 30 years. Plus, his sexual function improved —a common outcome of the treatment. As I’ve said before, when blood flow gets better anywhere in the body, it typically gets better everywhere.

YOUR GENES DON’T HAVE TO BE YOUR DESTINY

About 20 years ago, I was on a committee of a professional medical society, advocating for the use of neuroimaging tools like SPECT for the diagnosis of Alzheimer’s disease and other memory disorders. I argued that people should have access to more information about their own health and that SPECT was one of the best tools to evaluate brain function. One of my colleagues from a major Midwestern university disagreed. He suggested that since there was nothing people could do about the risk, there was no point in worrying them. It turned into a heated discussion because I believed then, and know now, that you can take a number of steps to decrease your risk.

In the BRIGHT MINDS mnemonic, G is for genetic risk factors. Humans receive 23 pairs of chromosomes —one set from each parent —that are found in the DNA in the nucleus of cells. Each chromosome contains the genes that provide instruction, or coding, for producing the different kinds of proteins that make up our cells. A healthy person has just the right number of chromosomes and the right number of genes. When the number of chromosomes is wrong, or there are extra or defective genes, health problems occur.

People who have family members with severe memory problems, Alzheimer’s disease, or another form of dementia, or those who have one or two copies of the APOE e4 gene or several other genes, have a higher risk for memory problems. This is especially true for those with a first-degree relative (mother, father, brother, or sister) with memory issues. They are 3.5 times more likely to develop symptoms. A family history of Parkinson’s disease also makes it more likely that people will develop memory issues. A recent study revealed that people with first-degree relatives with Parkinson’s disease were six times more likely to develop dementia than those in the general population.[249]

I think of the brain as a magnificent, complex series of spiderwebs (nerve cell fields) suspended in water, with neurons communicating at speeds of up to 268 miles per hour. Two of the prevailing theories about what causes severe memory loss include (1) the abnormal accumulation of beta-amyloid plaques —think of beta amyloid as a sticky, gooey substance that gets dropped into nerve cell fields, causing short circuits; and (2) twisted tangles of tau proteins within brain cells, called neurofibrillary tangles, that disrupt brain cell function.

For years, researchers have debated whether beta-amyloid plaques or tau proteins lead to severe memory loss. At times the hostility between the two camps has grown as bitter as a religious war, with some calling it a battle between the “baptists” (beta-amyloid believers) and the “tauists.” It now seems that both mechanisms are important, but cleaning up beta amyloid and toxic tau proteins after a person develops memory issues has not helped in human studies.[250] They must be purged as early as possible, before they short-circuit brain cell networks.

At least four genes are known to increase beta-amyloid production:

  1. the e4 version of the apolipoprotein E (APOE) gene on chromosome 19, which is associated with late-onset Alzheimer’s disease[251]
  2. the amyloid precursor protein (APP) on chromosome 21, which is overproduced in people with Down syndrome, sometimes causing memory problems between the ages of 35 and 65
  3. the presenilin 1 gene on chromosome 14 (PSEN1), which often causes Alzheimer’s disease
  4. the presenilin 2 gene on chromosome 1 (PSEN2), which also often causes Alzheimer’s

Tau proteins are found inside neurons and provide the structure, like train tracks, to help cells expel unwanted and toxic proteins. When tau proteins function properly, they clear the cells of toxic proteins such as beta amyloid. When they act abnormally, the tracks fail, trash accumulates, and damage occurs,[252] sort of like a car wreck. Tangled and abnormal tau deposits can result from repeated head trauma, which is found in football players with dementia (also called chronic traumatic encephalopathy, or CTE).[253] Besides trauma, errant genes on chromosome 17 can cause tau protein problems, as can excessive iron stores.[254]

The APOE gene: do you have an e4?

Everyone has two APOE genes. These genes alone are not dangerous; we need them to function. They help in the development, maturation, and repair of cell membranes. They also help regulate the amount of cholesterol and triglycerides in nerve cell membranes.

There are three versions of the APOE gene: e2, e3, and e4. As with all genes, we inherit one copy from each parent, which means everyone has one of the following combinations:

e2/e2

e2/e3

e2/e4

e3/e3

e3/e4

e4/e4

A person with one APOE e4 gene inherited it from one parent. Someone with two APOE e4 genes received one from each parent. A person with one APOE e4 —or worse, two genes —has a high chance of experiencing memory problems. This gene increases the beta-amyloid deposition and plaque formation that are found in the brains of people with Alzheimer’s disease, so it increases the chance of developing late-onset Alzheimer’s disease —by 2.5 times if you have one e4, or 5 to 15 times if you have two e4s.[255] For people who carry the APOE e4 gene but whose Alzheimer’s is due to other causes, symptoms appear two to five years earlier than in people without the gene.

About 15 percent of the population has at least one APOE e4 gene. With just one APOE gene, the odds of developing Alzheimer’s after age 65 are 25 percent, versus a 5 to 10 percent risk for people with no APOE e4 gene. That’s quite a difference. But there is good news: Not everyone with the gene will develop Alzheimer’s disease; in fact, 75 percent will not. Even if someone with one APOE e4 gene develops dementia, the cause may be something other than Alzheimer’s disease. However, if someone with two APOE e4 genes develops dementia, the odds are high that Alzheimer’s disease is the culprit. In fact, having two e4 copies may increase the risk of developing Alzheimer’s by 12 times. Having one or two copies of the APOE e4 gene also increases the risk of vascular problems.[256] The APOE e4 gene is associated with overall lower blood flow to the brain,[257] which means it is absolutely essential that people with this gene take good care of their blood vessels.

The presenilin genes (PSEN1 and PSEN2): another route to Alzheimer’s disease

Two other genes, presenilin 1 and 2 (PSEN1 and PSEN2), have been found in families where a number of members have Alzheimer’s disease. PSEN1 is on chromosome 14, while PSEN2 is on chromosome 1. Both of these gene mutations greatly accelerate beta-amyloid production. PSEN1 causes symptoms to appear early, when people are between the ages of 35 and 55. The PSEN2 gene is rarer, and dementia symptoms may appear early or late, between ages 40 and 85.[258]

EPIGENETICS MAY BE JUST AS IMPORTANT

For the past few decades, scientists have been exploring the new field of epigenetics, or the way behaviors, emotions, and environment can turn certain genes on or off. As a result, some illnesses become more or less likely, in us as well as in our children, grandchildren, and even great-grandchildren. Geneticists now know that our habits, feelings, and environment affect our biology so deeply that they cause changes in the genes that are transmitted to future generations. These epigenetic “etches” tell your genes to switch on or off or to express themselves more loudly or softly.

In other words, environmental factors like diet, stress, toxins, and prenatal nutrition can affect the activity of the genes that are passed on to your offspring and beyond. A 2006 study demonstrated that prepubescent boys (age 11 or 12) who started smoking cigarettes increased the risk of obesity in their children.[259] Unwise decisions at such a young age could affect future generations. And obesity[260] is just the beginning. Some researchers believe that epigenetics could also help us better understand certain cancers, forms of dementia, schizophrenia, autism, and diabetes.[261]

CHECKUP FOR GENETICS ISSUES

Know your family history

Not everyone has taken the time to find out what happened to Aunt May or Great-Uncle Willie. Reach out to family members so that you can be aware of any branches of your family tree in which memory troubles have appeared —and address those issues, if necessary.

Lab test

The Strategies

  1. 1. Go for screening early. For those who have genetic risk factors (a family history of memory problems, dementia, or Alzheimer’s), early screening —around age 40 —that includes questionnaires, cognitive testing, and possibly brain SPECT imaging is important. New research shows that having the APOE e4 gene is not necessarily a dementia death sentence.[263] Early screening gives you a window in which to address the other risk factors.
  2. 2. Take your brain health seriously. If you suspect you have a genetic predisposition to memory issues, caring for your brain is critical. Studies have shown that the risk of dementia was significantly lower in people with one or two of the e4 variants of the APOE gene if they had higher education levels and engaged in leisure activities like sports or hobbies that involved new learning. They also did better if they took care of their blood vessels and had fewer vascular risk factors, such as hypertension, smoking, or heart problems.
Bright Minds Tip icon

Being hypervigilant about keeping your brain healthy could make all the difference, particularly if you’ve watched family members struggle with dementia.
  1. 3. Hop on the exercise bandwagon. Research has found that physical exercise can decrease beta-amyloid buildup in the brain in APOE e4 carriers.[264] Research teams in Finland and Sweden found that exercising at least twice a week in middle age lowered the chance of getting dementia more than 20 years later, and this protective effect was stronger in people with the APOE e4 gene. All of us should exercise, engage in new learning, and take care of our blood vessels, but it is even more imperative if you have one or two APOE e4 genes.
  2. 4. Avoid head trauma. To protect your head from injuries and concussions (which can increase abnormal tau proteins), avoid contact sports and falls, which are much more common as you age. Practice balance exercises and strengthen your muscles to keep them in shape.

The Nutraceuticals

The following nutrients have been shown to decrease beta-amyloid plaque formation and tau protein deposits in animal studies:

The Foods

AVOID (OR LIMIT):

CONSIDER ADDING:

PICK ONE HEALTHY BRIGHT MINDS HABIT TO START TODAY

  1. If you have dementia in your family, be serious about brain health starting now and get early screening for memory problems.
  2. Test your APOE gene type.
  3. If you have the APOE e4 gene, avoid contact sports or other head trauma risks.
  4. Limit high-glycemic, saturated-fat foods, such as pizza.
  5. Limit processed cheeses and microwave popcorn.
  6. Take a curcumin supplement to decrease beta-amyloid plaques before they damage your brain.
  7. Eat organic blueberries to decrease beta-amyloid plaques.
  8. Cook with sage to decrease beta-amyloid plaques.
  9. Take a ginseng supplement.
  10. Take a coenzyme Q10 (CoQ10) supplement.