The End of Alzheimer's

date Sep 20, 2022
authors Dale Bredesen
reading time 11 mins
health

Definition

Why Alzheimer’s should be paid attention to

First, it is the only one—let me repeat that: the only one—of the nation’s ten most common causes of death for which there is no effective treatment.

No initial treatment

We don’t even have a treatment to keep people with subjective cognitive impairment or mild cognitive impairment (two conditions that often precede Alzheimer’s disease) from going on to develop full-blown Alzheimer’s.

Years and decades before death

For years and sometimes decades before it opens the door to the grim reaper, Alzheimer’s disease robs its victims of their very humanity and terrorizes their families.

Reversal of cognitive decline in early stages

I expect you to exercise that skepticism as you read about the three decades of research in my lab, which culminated in the first reversals of cognitive decline in early Alzheimer’s disease and its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment).

Genetic link

ApoE4 is the strongest known genetic risk factor for Alzheimer’s disease. Carrying one ApoE4 (that is, inherited from one parent) increases your lifetime risk of Alzheimer’s to 30 percent.

10% above 65 years old

Because Alzheimer’s disease strikes an estimated one in nine Americans 65 and older, or 5.2 million people as I write this, the aging of the baby boom generation threatens to bring a tsunami of Alzheimer’s

Trying to get rid of amyloid is not helpful

the amyloid that has been vilified for decades, the very amyloid that everyone has been trying to get rid of, is part of a protective response. No wonder trying to get rid of it hasn’t been very helpful to those with Alzheimer’s disease.

Protective response

Alzheimer’s disease is actually a protective response to, specifically, three different processes: inflammation, suboptimal levels of nutrients and other synapse-supporting molecules, and toxic exposures.

How Alzheimer’s is different from other diseases

the disease we call Alzheimer’s is actually the result of a protective response in the brain. This is worth repeating. Alzheimer’s disease does not arise from the brain failing to function as it evolved to. It is not like cancer, where a genetic mutation—inherited or acquired during the course of life—turns.

Stages and types

Early stages

Memory loss is often one of the earlier symptoms, which typically include difficulty with reading, writing, speaking, following a conversation, reasoning, calculating, organizing, and planning.

Types of dementia

There are many causes of dementia, including vascular dementia, frontotemporal dementia, Lewy body dementia, and others, but Alzheimer’s disease is the most common.

  • Vascular dementia: The form of dementia caused by reduced blood flow to the brain and marked by multiple small strokes.
  • Frontotemporal dementia: This is much less common than Alzheimer’s disease, and often features changes in behavior, memory problems, and difficulty speaking.
  • Lewy body dementia: This is a fairly common cause of dementia (about one patient for every five Alzheimer’s patients), and features visual hallucinations, delusions, increased sleeping, and flinging of limbs during sleep (called REM behavioral disturbance), among other features.
  • Alzheimer’s disease: This form of dementia is marked by amyloid plaques and neurofibrillary tangles.

2 types of cognitive impairment:

  • Subjective cognitive impairment (SCI): Worsening cognition that is noticeable to the individual but, in standard neuropsychological testing, still falls in the normal range.
  • Mild cognitive impairment (MCI): This typically follows subjective cognitive impairment. Neuropsychological tests show that memory, organizing, speaking, calculating, planning, or other cognitive abilities are abnormal, but the person is still able to perform the so-called activities of daily living,

Early symptoms:

  • Facial blindness or prosopagnosia
  • Decreasing mental clarity
  • Decreasing interest in reading
  • Decreasing ability to recall what she read or heard
  • Decreasing vocabulary
  • Mixing up words
  • Decreasing processing speed
  • Increasing anxiety about driving and finding her way
  • Difficulty remembering to-do list and appointments
  • Sleep disruption
  • No longer getting a mental boost from caffeine
  • Trouble speaking the foreign languages
  • Difficulty recognizing and remembering faces

Why would so many of the very genes that distinguish us from our primate cousins—that, in other words, make us distinctly human—turn out to promote inflammation?… because few lived long enough and in part because their lifestyles actually covered many of the thirty-six holes—they led much less sedentary lives, ingested far fewer simple carbohydrates, had no processed foods, and had much less toxic exposure.

Causes

Other factors that contribute to Alzheimer’s

  • diet
  • activity
  • stress
  • cardiovascular health
  • general health
  • prediabetes
  • obesity
  • vitamin D deficiency
  • sedentary lifestyle
  • inflammation
  • hormonal imbalance
  • toxic exposure
  • folate deficiency

Synapses

When we are young, these two processes—synapse building/maintenance and synapse dismantling—are in dynamic equilibrium. When we learn, synapses are formed and strengthened… As we age, however, the inputs needed for synaptic growth and maintenance—hormones, nutrients, and more—grow more scarce.

Preserve life sustaining functions

To anyone suffering from Alzheimer’s, of course, it is small comfort to know that the brain made a deliberate “choice” to preserve life-sustaining functions at the expense of the abilities—remembering and thinking, understanding and imagining—that make us human.

Last hired, first fired

As in corporations that follow a “last hired, first fired” philosophy of layoffs, recent memories go first, older ones next, and the oldest ones last. Thus Alzheimer’s patients often remember their childhood of eighty years ago better than the breakfast they had an hour ago.

Prevention / Reversal

Instead of a single pill, we proposed that we combine tropisetron with the forerunner of ReCODE: a comprehensive program of nutrition, exercise, synapse-supporting supplements, hormonal optimization, specific herbs, sleep optimization, and stress reduction, all aimed at shifting the brain’s balance from synapse destruction to synapse preservation by removing the contributors

Apoe4 gene symptoms

In people who carry two copies of ApoE4, symptoms often begin in the late forties or fifties. For people who carry one copy of ApoE4, symptoms typically begin in the late fifties or sixties. For those with no copies of ApoE4, symptom onset is typically in the sixties to seventies.

Levels of homocysteine

Keeping your homocysteine optimally low requires sufficient levels of vitamins B6, B9 (folate), and B12, all in their active forms.

Folate

For folate, the “normal” range is 2–20 nanograms per milliliter, but again, you don’t want to be at the low end of normal. Aim for 10–25.

Insulin and glucose

High insulin and high glucose are two of the most important risk factors for Alzheimer’s disease.

Vitamin D

Reduced vitamin D activity is associated with cognitive decline. Vitamin D travels through your blood and tissues like a Wi-Fi signal, entering your cells… GOAL: vitamin D3 (measured as 25-hydroxycholecalciferol) = 50–80 ng/ml.

Thyroid

Optimal thyroid function is crucial for optimal cognition, and suboptimal thyroid function is common in Alzheimer’s disease. OPTIMAL: TSH < 2.0 microIU/ml; free T3 = 3.2–4.2 pg/ml; reverse T3 < 20 ng/dL; free T3 x 100:reverse T3 > 20; free T4 = 1.3–1.8 ng/dL.

Copper and zinc

Too much copper and too little zinc are associated with dementia. Professor George Brewer from the University of Michigan has spent his career studying the effects of copper and zinc on cognitive function, discovering that most of us are deficient in zinc but have excess copper.

Avoid mercury fish

(The larger the fish and the longer it lives, the more mercury it typically has, so tuna, swordfish, orange roughy, and shark are of particular concern, whereas the “SMASH fish”—salmon, mackerel, anchovies, sardines, and herring—are safer.)

Sleep

Sleep affects cognition through multiple fundamental mechanisms: It alters the cellular anatomy of your brain, allowing a cleansing… Sleep is also associated with a reduced formation of the amyloid.

Intermittent fasting

don’t eat when we’re asleep. Fasting improves our insulin sensitivity. During sleep, our brain cells activate autophagy, the process of “self-eating” that recycles cellular components

Horomones during sleep

Sleep is also a time of repair. Growth hormone increases during sleep, repairing cells, and new supportive brain cells are produced during sleep, among the many reparative processes that occur during sleep.

Link with vascular disease

many people with “high cholesterol” have no problem with vascular disease, and many with “normal cholesterol” have significant vascular disease. Vascular disease itself is a contributor to cognitive decline, because it raises the risk of Alzheimer’s disease and can cause vascular dementia, which is typically associated with many small strokes.

Cholesterol is important

When total cholesterol falls below 150, you are more likely to suffer brain atrophy—shrinking. Cholesterol is a key part of cell membranes, including those of brain cells. What you don’t want is damaged cholesterol and its related lipid particles—these

BMI

An unhealthy body mass index (BMI) raises your risk for cognitive decline. You can find simple online calculators or do it yourself.

Combination of tests

the combination of blood tests, genetic tests, simple online cognitive assessment, and MRI with an automatic computer assessment of brain volumes provides crucial clues to what is causing cognitive decline or putting you at risk for it.

Lifestyle with diet, exercise, fasting

To promote ketosis, you combine a low-carbohydrate diet (minimizing simple carbs such as sugars, bread, white potatoes, white rice, soft drinks, alcohol, candy, cakes, and processed foods), moderate exercise (at least 150 minutes per week of brisk walking or something more vigorous), and fasting for at least twelve hours between your last meal of the night and your first of the next morning (more on this in a minute).

Benifit of fasting

Another big benefit of fasting for 12 to 16 hours is that it promotes autophagy, in which cells (including those in the brain) recycle components and destroy damaged proteins and mitochondria—which is good for renewal.

Whole fruits for fiber

Avoid fruit juices in favor of whole fruits (which include the fiber). Fruit smoothies are fine, but don’t make them too sweet (that contributes to insulin resistance).

Awesome fruits

The best fruits are wild, colorful berries, lemons, limes, tomatoes, and avocados (yes, tomatoes and avocados are, strictly speaking, fruits).

Avoid tropical fruits

Ancestrally, fruits were consumed at the end of summer to fatten for the winter. Avoid tropical fruits because of their increased glycemic index.

Detoxifying plants

These detoxifying plants include cilantro, cruciferous vegetables (cauliflower, broccoli, various types of cabbage, kale, radishes, Brussels sprouts, turnips, watercress, kohlrabi, rutabaga, arugula, horseradish, maca, rapini, daikon, wasabi, bok choy), avocados, artichokes, beets, dandelions, garlic, ginger, grapefruit, lemons, olive oil, and seaweed.

Probiotics and prebiotics

After healing your gut (described below), you need to optimize the bacteria there, which includes feeding the right bacteria (probiotics) with the right bacteria food (prebiotics).

Probiotics

For the probiotics, those include fermented foods such as kimchi, sauerkraut, sour pickles, miso soup, and kombucha… It is often helpful to include in your diet a yeast called Saccharomyces boulardi, which functions as a probiotic, especially if you have diarrhea.

Prebiotics

Prebiotic foods include jicama, onions, garlic, raw leeks, raw Jerusalem artichoke, and dandelion greens.

Benefits of exercise for cognition

  • Exercise reduces insulin resistance
  • It increases ketosis, which, among other effects
  • It increases the size of the hippocampus
  • It improves vascular function, which is crucial for neuronal and synaptic health.
  • It reduces stress, a key trigger of Alzheimer’s-promoting inflammation.
  • It improves sleep, another necessity for cognitive health.
  • It increases the survival of newborn neurons
  • It improves mood.

Optimal exercise for cognition

What is the optimal exercise for cognition? You want to combine aerobic exercise, such as jogging or walking or spinning or dancing, with weight training, preferably at least four or five days per week, for 45 to 60 minutes in total each day.

Anti-inflammatory foods

There are many other anti-inflammatories, such as ginger, cinnamon, pregnenolone, cloves, thyme, as well as anti-inflammatory foods such as green leafy vegetables, beets, and broccoli.

Fasting

  • I drink a glass of room temperature water with lemon and/or ginger to detoxify
  • Sip organic Japanese green tea and one cup of bone broth (fat removed) throughout the day, but refrain from snacking.