Reversing Cognitive Decline and Preventing Alzheimer’s

You saw a movie last week and in discussing it with friends simply can’t remember the important parts. Plus you just missed another appointment. Planning to drive to a north suburb, you instead got on the southbound expressway and after 15 minutes of Loop traffic realized your error. You’re mixing up words and forgetting too many names. Reading anything has shifted from pleasure to struggle. You see someone you ought to know but you’re unsure who they are. When you learn it’s someone you’ve known for years, you’re shocked and embarrassed.

And you’re really not all that old. 40s? 50s? Didn’t grandma, now dead after a decade in a nursing home, starting showing signs of senility in her 60s? Many of us lose some of our smarts as we age, but certainly not necessarily. Chicago icon and brilliant polymath Studs Terkel remained as sharp as a tack until he passed away at 96, likely with a martini and cigar at his bedside.

Why the difference and what’s the latest?

Are some of us just doomed to slowly deteriorate mentally while others are blessed with active and inquisitive brains until the end? You can learn a great deal about your brain and how to care for it in what I believe is the most important medical book published this past year, The End of Alzheimer’s, by Dale Bredesen, MD.

Based on microscopic examination of autopsy brain specimens, and more recently PET scans on living people, physicians thought brain deterioration occurred because of an accumulation of a protein called amyloid, which damaged delicate brain cells. They reasoned that if a medication could be developed to dissolve, or at least halt, amyloid production then Alzheimer’s could be cured or slowed down. Unfortunately, after extensive clinical trials, this route met with little success.

Other drugs that are designed to increase certain brain chemicals, like Aricept and Namenda, marginally improve memory but don’t stop Alzheimer’s.

After years and years of study, Dr. Bredesen concluded that researchers were on the wrong track. Amyloid production in the brain occurs when the brain is assaulted by any of several triggers. It’s a defense mechanism gone awry. To some extent, the triggers he describes can cause cognitive decline in just about anyone, but some people are more reactive to these triggers than others. Once assaulted, their sensitive brains pump out amyloid, triggering the fast-forward button of cognitive decline.

There are different manifestations of this decline. The mildest, called subjective cognitive impairment (SCI), means that you yourself notice something’s wrong, but really no one else does. For many of us, SCI feels like just a part of getting older, and fortunately may not lead to Alzheimer’s.

A little more serious is mild cognitive impairment (MCI), noticed by you and others. Again, not everyone with MCI develops full-blown Alzheimer’s, but many do.

Patients with MCI have lower-than-perfect scores on the Montreal Cognitive Assessment Test  (MoCA), which can be administered by a physician or psychologist. It’s one of several tests available and for a thorough exam, more than one type of test should be administered.

What’s attacking the brain?

So if amyloid production with subsequent loss of brain function is a brain defense mechanism gone awry, what exactly is attacking your brain, and why yours?

To some extent, though not completely, it’s genetic. SCI, MCI, and Alzheimer’s can run in families, but for many patients there may be no other family members affected. If there is a genetic villain, it’s APOe4. There are actually four APOe genes (labeled 1 through 4). Keep in mind that you get one gene from each parent, and you can get tested to see what you have. Most people carry APOe3/3 and this poses no increased Alzheimer risk. However, APOe3/4 increases Alzheimer’s risk by two to three times. APOe4/4 increases the risk 12 times.

WholeHealth Chicago patients can contact their primary care provider and schedule APOe testing in our lab. Generally, insurance picks it up but always keep an eye on your deductible. Alternatively, order the 23andMe Health + Ancestry Service for $229, which includes this profile.

It’s important to recognize these facts

1. You can experience cognitive decline and even develop full-blown Alzheimer’s without any evidence of APOe4 risks.
2. If you do have either of the APOe risks, there are important–very important–steps you can take to reduce the risk of your genes manifesting themselves as cognitive decline.
3. If you’re already experiencing some cognitive decline, whether it’s subjective or mild, and you have a less-than-perfect MoCA, or even early Alzheimer’s, you can prevent further damage and even reverse this deterioration.

Inflammation and Alzheimer’s

As mentioned above, the current thinking about cognitive decline, whose worst manifestation, Alzheimer’s disease, occurs because a protein called amyloid accumulates in the brain, destroying delicate brain cells. Focusing on clearing out amyloid as a treatment of Alzheimer’s has been unsuccessful. The answer is prevention.

In his important book The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline, Dale Bredesen, MD, a UCLA-trained research neurologist, shows that amyloid appears as a reaction to any of several threats to our brain. He divides these threats into three groups.

Three main threats to the brain

The first, and most important, is chronic inflammation. You’ve probably read a lot about inflammation.

There are two forms of inflammation, one that helps us and one that harms. Brief episodes of inflammation are described as acute. These include your body’s elegant, normal response to any attack, whether by a bacterial or viral infection or to a foreign body, such as a splinter in your thumb. In medical vocabulary, adding “-itis” to a body part indicates an inflammation is taking place. Think appendicitis or dermatitis.

Chronic inflammation is the harmful version, now known to be the villain behind heart disease, autoimmune disease, and some cancers. Last week I mentioned that individuals carrying a specific gene–APOe4–are especially susceptible to brain inflammation and subsequently to Alzheimer’s. But susceptibility isn’t the same as inevitability. Certainly not all APOe4 carriers get Alzheimer’s (or any form of cognitive decline) and plenty of Alzheimer patients do not carry the APOe4 gene.

Dr. Bredesen has compiled an extensive list of triggers that create the chronic inflammatory state capable of igniting the smoldering fire of cognitive decline and Alzheimer’s. These include chronic infections like chronic Borrelia (Lyme disease), Herpes simplex (cold sores), chronic sinusitis, and even gingivitis (gum disease).

Equally risky triggers for inflammation in susceptible people are dietary (gluten grains, trans fats, sugars, dairy). Gluten, for example, can inflame the lining of your intestine, rendering it more permeable to a variety of other inflammatory foods, a condition called leaky gut. Too much sugar or too many simple carbohydrates (such as white bread), which convert to sugar, can cause your body to become resistant to the sugar-lowering effect of insulin. This is insulin resistance, which we now know can increase amyloid deposition.

How much inflammation you have in your body and discovering what’s triggering it can be established with lab tests, part of a diagnostic protocol Dr. Bredesen dubs a cognoscopy, sort of a colonoscopy of your brain.

Atrophic threats. Keeping in mind that amyloid appears as a reaction to any of several threats to our brains, Dr. Bredesen describes this second risk group using the medical word atrophic, meaning gradual decline in function due to neglect or underuse. This, too, occurs more often among APOe4 carriers.

The neglect list can be pretty long, but it’s manageable. Neglect includes an unhealthful diet; vitamin deficiencies such as low B-12, vitamin D, and vitamin E; smoking; homocysteine levels; and lower-than-normal levels of virtually every hormone our bodies manufacture (thyroid, adrenal, estrogen, progesterone, testosterone, pregnenolone).

The underuse list can pretty much be summed up by the phrase “use it or lose it.” Challenging your brain constantly keeps it vital and healthy. Sitting slack-jawed in your recliner binge watching and binge eating is risking trouble. Dr. Bredesen recommends a variety of brain exercise websites, such as BrainHQ, and let me also remind readers that uncorrected hearing loss has been associated with early dementia.

Toxic threats. Bredesen’s third Alzheimer’s threat occurs more frequently in carriers of the fairly common APOe3 gene rather than APOe4. This type of Alzheimer’s is less common and usually begins earlier, in the late 40s and 50s. It often starts after a period of physical or emotional stress. The initial symptoms may be difficulty with spelling, reading, word-finding, or simple arithmetic. Significantly, people in this group have blood-test abnormalities in tests not normally performed as part of a dementia diagnostic work-up.

Among these are low levels of zinc, high levels of copper, adrenal gland abnormalities, and a history of excessive exposure to toxins like mercury or black mold (mycotoxins). Here’s a page that shows good food sources of zinc.

Do I need a cognoscopy?

You might reasonably ask who really should get tested for all this. Who really needs Dr. Bredesen’s cognoscopy?

First, if there’s dementia in your family start with APOe testing. Obviously you’ll not be thrilled if you learn you’re carrying the APOe4/4 gene, but knowing you’re at risk means you can start taking preventive steps immediately. If you have a positive test result for APOe4/4 or APOe4/3, further tests can be individualized according to your age, gender, and lifestyle.

Second, if you’re experiencing cognitive decline, either the subjective form (you sense it but others don’t notice) or the mild type (noticed by you and others), step right up and get a thorough battery of tests (Bredesen’s cognoscopy).

Tests for Alzheimer’s Prevention

Dale Bredesen, MD, author of The End of Alzheimer’s: The First Program To Prevent and Reverse Cognitive Decline, refers to the tests you should undergo if you’re concerned about brain health as a “cognoscopy,” sort of a colonoscopy for your brain. Perhaps thinking back on your own colonoscopy, it’s reasonable to ask, “Do I really need a cognoscopy?”

There are three groups of people I recommend give these tests serious consideration. (And at least a cognoscopy doesn’t require a laxative.)

• If mid- or late-life dementia runs in your family. (“Grandma was showing confusion in her late 60s and spent her final ten years in a nursing home.”)
• You’re middle aged and experiencing too many senior moments. No one else notices, but you do, which is why it’s called subjective cognitive impairment.
• You’re middle aged and people around you have expressed concern about changes in your cognitive skills (missed appointments, late for meetings, third iPhone replacement). This is mild cognitive impairment.

Although it’s been long established that a protein called amyloid deposited in your brain is the culprit behind the dementia that characterizes Alzheimer’s, there are three primary amyloid triggers: inflammation, atrophy, and toxins.

Before you do any detailed testing, ask your doctor to check your APOe (the Alzheimer gene) status. While dementia can occur among APOe-negative patients, being APOe-positive can increase your risk dramatically.

Here are tests for inflammation

Click on the links to learn more.

• hsCRP (high sensitivity C-reactive protein) measures inflammation throughout your body.
• A/G ratio (ratio of albumin to globulin), a test that complements the hsCRP.
• Ratio of omega 6 to omega 3 fatty acids in your blood cells (ditto).
• IL-6 (interleukin 6) and TNF (tumor necrosis factor), both of which increase during chronic inflammation.
• Gluten sensitivity (though simply eliminating gluten for 14 days and finding you feel better and then re-introducing it and feeling worse is an excellent self-test).
• Leaky gut (intestinal hyperpermeability).

Tests for atrophy (nutritional and hormonal deficiencies)

• Vitamins B-1 (thiamine); B-6; B-12; D; E; and folate.
• Thyroid: Free T3, Free T4, TSH, reverse T3, thyroid antibodies.
• Sex hormones: estradiol, progesterone, testosterone, DHEA, pregnenolone.
• Adrenal hormones: AM and PM cortisol, the stress hormone (via the Genova Adrenocortex Stress Profile).
• Homocysteine (an amino acid linked to brain atrophy, which can be lowered by taking adequate amounts of B vitamins).
• Fasting insulin; fasting blood sugar; HbA1c (hemoglobin A1c). All test for insulin resistance and early diabetes, both common with early dementia.
• Serum zinc, copper, glutathione, selenium, red blood cell magnesium. 

Tests for toxins (chronic infections, environmental toxins)

• Mercury (inorganic mercury=dental fillings; methyl mercury=fish).
• Arsenic, lead, cadmium.
• Lyme disease screening.
• Mycotoxin (black mold sensitivity) screening.
• C4a (inflammatory marker for Lyme and mold toxicity).
• TGF-Beta 1 (inflammatory marker).
• HLA-DR/DQ (genetic test for susceptibility to chronic inflammation of Lyme and mold).
• Intestinal microbiome (gut bacteria).

Other useful dementia-related tests

• Hearing (long-term hearing loss increases risk for dementia).
• Cholesterol profile (high LDL increases risks for dementia caused by multiple small strokes).
• Sleep study (untreated sleep apnea can cause brain amyloid deposits).
• MRI of brain with measurements of brain volume (for people at high risk or who have mild cognitive decline).
• Professional screening of your mental status by a psychologist.

Will your health insurance pay for all this? In fact, most of the tests listed above are not considered alternative or experimental and indeed are covered by most PPO policies, although with health insurance nothing is for certain.

It’s easier to list tests that are only partially covered: the functional tests for leaky gut and adrenal function. Not covered by insurance are the confirmatory tests for Lyme (Igenex) and mold (Great Plains Mycotox Profile).

If you have concerns about your susceptibility to Alzheimer’s, print this series of Health Tips and take them to your primary care physician. Read Dr. Bredesen’s book and encourage your doc to read it as well.

If you’re interested having these tests at WholeHealth Chicago, schedule with any of the WholeHealth Chicago Providers.

Once we have your test results back, nutritionists Tam Dickson will be added to your team.

Reversing Mental Decline – Nine Immediate Steps to Prevent Dementia

We’ve covered a lot of scientific territory in this Health Tip, from the basics of Alzheimer’s to the tests used to evaluate risk. This final installment is something you can follow up on right now, regardless of where you fall on the risk spectrum.

Concerning your brain, let’s say you’re in one of these four situations:

• There’s dementia in your family and you’ve checked your APOe gene risk and found you’re at increased risk (APOe 4/4 or 4/3).
• There’s dementia in your family, but you don’t want to know your APOe status.
• There’s no dementia in your family, but you’ve been experiencing some cognitive symptoms that are either so mild no one notices or you’ve had symptoms that might be interfering with your life.
• You have none of the above, but do want your brain to function at its maximum potential for your entire (and very long) life.

Everyone listed above will benefit from following these steps to support best brain function.

1. Get regular physical exercise.  Yes, I know, you hear this all the time, but the data showing that exercise prevents dementia grows ever more compelling. Just last week a Swedish study showed that women who were highly fit in middle age were 90% less likely to get dementia in their later decades than those who were deconditioned or even moderately fit. 90%?! That should motivate you to walk outside several times daily, always take the stairs, and do some form of high-intensity workout. This one can be managed by people of virtually every age and ability in any location.
2. Tamp down the stress.  Chronic stress from any source definitely increases your dementia risk. Make life choices based on how you answer “Will the result of this choice increase or decrease my stress levels?” Planning to get engaged to a heroin addict you’re sure you can change? Pondering a well-paying job in the Trump administration? Get counseling if you need help making life-changing and potentially stress-inducing decisions.
3. Eat a ketogenic diet.  If you’ve read the words “going keto,” that’s how you’ll be eating. Your liver starts making specific chemicals called ketones from stored fats when it’s running low on carbs. Blood levels of ketones increase, a condition called ketosis, and your brain function improves. Read more about the ketogenic diet here. There are two steps to producing more ketones. First, switch to a low-carbohydrate, high-fat, moderate-protein diet. Second, incorporate intermittent fasting and go NPO (that’s nothing by mouth except water) for 12 hours or more every day. Finish dinner by 7 pm and hold off eating breakfast until 7 am or even later.
   • In addition, because gluten triggers unnecessary inflammation, avoid it. Most of us can handle dairy, but purchase high-quality (organic or grass-fed) versions of milk, cream, and cheeses. Keep saturated fats low by using high-quality grass-fed beef and pastured chicken as a condiment rather than as a main course. Eating a keto diet, you’ll learn to focus on lower-carb vegetables and lower-sugar fruits while you increase the amount of good fats you consume by eating more fish and avocados and using olive oil and other healthy fats. This is low-inflammation eating. If all this seems daunting, our WholeHealth Chicago nutritionists can help you make sense of it.
4. Master the art of good sleep.  It starts with a dark cool room, a quiet environment, limiting screen time, and being in bed before midnight. And since just about everyone over 45 wakes up sometime between 1 and 3 am, don’t agonize over it. Go empty your bladder, get back into bed, and meditate. Morning will come.
5. Make a conscious effort to reduce your body’s inflammation. Interestingly, some people can sense when they’re inflamed because they have symptoms like fatigue, general achiness, skin eruptions, brain fog, and digestive problems. Your doctor can measure your inflammation with an hsCRP test. If yours is elevated, you and your doctor will need to play detective to find the sources. The big villains of inflammation are eating a nutritionally poor diet, leaky gut syndrome, chronic infections (like Lyme disease, mold, chronic viruses such as herpes and Epstein-Barr, poor oral hygiene, and chronic sinusitis), and autoimmune diseases (like rheumatoid arthritis, lupus, and Hashimoto’s).
6. Get your hearing checked and your teeth regularly cleaned. Untreated hearing loss equals diminished brain function, which in turn increases dementia risks. Floss daily.
7. Keep your hormones (thyroid, adrenal, sex hormones) at healthy levels. You may have to apply pressure to your doctor for cooperation on this, but “borderline hypothyroid” is not normal. For women, long-term sex hormone replacement (starting at the onset of menopause) definitely reduces dementia risks. Ask your doctor for bioidentical hormones. You’ll be taking a molecule that’s completely identical to the one your ovaries were producing. Read more about bioidentical hormones replacement here. Because there’s an increased risk of breast cancer theoretically with any hormone replacement (1.2 times the average risk), annual mammograms are mandatory. Bioidenticals are not owned by Big Pharma, so all the studies testing the risks of hormone replacement have used the pharmaceutical Premarin. No one has performed a head-to-head study comparing the risks of Premarin with those of bioidenticals.
8. Keep your exposure to chemicals very low. If not you’re not buying organic, which is ideal, wash fruit and veggies thoroughly. Most of what you’ll eat on a keto diet are whole foods, but if you’re buying a food with a label, read it closely. If you can’t pronounce something or if it’s another word for sugar, don’t eat it. Challenge the necessity of any drugs you’re prescribed. More than three quarters of Americans over age 50 are taking one or more prescription drugs, most of them prescribed to treat the consequences of unhealthful lifestyle choices.
9. Challenge your brain endlessly. Watch less TV and check your phone less often. Read more books, take some evening courses, join a choir, create art or write in a journal, and learn something new, like a foreign language or a musical instrument. Consider using one of the brain-fitness websites, such as brainhq.com.

Here’s a list of the basic nutritional supplements that most researchers, including Dr. Bredesen of The End of Alzheimer’s, consider most helpful for maintaining optimal brain health (all are available in our Apothecary):

• A high-potency multiple vitamin, with or without iron (with iron is only for menstruating women), such as Multiplex by Integrative Therapeutics.
• Vitamin D 5,000 IU daily
• Resveratrol Ultra–High Potency (by Integrative Therapeutics) 175 mg, one daily.
• Citicoline (by Jarrow) 250 mg, twice daily.
• SPM Active (ultra high-potency fish oil for inflammation), one capsule twice a day.

This list will likely be longer if you’re following the Bredesen Protocol (ReCODE) for restoring cognitive function and you’ve had some abnormal test results.

Whether or not you want to check your genetic risk with an APOe test is up to you. However, if you’re experiencing any memory issues, best get started on the lifestyle changes ASAP.

Be well,
David Edelberg, MD