Every day sometime after he's had a coffee and bite to eat and perused the news, 83-year-old Peter Wilson heads out to a Calgary nursing home to visit his wife, Jean. The staff all like Pete, who often brings in a box of donuts and tries to make them laugh.
There is no conversation with Jean, however. She might smile and say hello to Pete, but then she drifts away into a vacant place where no one can reach her. She doesn't read, and she can't follow anything nearly as complex as a television show. Pete settles into a comfy chair to read a spy novel.
"You don't have to yell," he says to a nurse shouting at Jean to sit down. "She can hear you. She just doesn't understand what you're saying." Jean is pleasant and cooperative compared to many of the Alzheimer's patients on the ward who have outbursts of confusion or anxiety. They put her headphones on, tuned to classical music, and Jean smiles, waves her hands in the air like a conductor, and is away again.
She's been gone for much of the last 15 of her 88 years.
There are millions of versions of this heartbreaking tale. Alzheimer's is one of the things people fear most about growing old, and statistics justify the concern: if you are an adult today, the odds are one in three that you will have Alzheimer's disease by the time you reach 85. Perhaps if you don't, you will be caring for someone who does.
More than 5.7 million people are living with Alzheimer's disease in the United States, where someone is diagnosed with the disease every 65 seconds.1 At that rate, that population will grow to 16 million by 2050. Globally, an estimated 47 million people live with dementia, and that number is expected to double every 20 years, surging to over 130 million by 2050.2
Although it doesn't kill suddenly, Alzheimer's slowly steals memories, creativity, processing faculties and identity—then it claims lives. It is now the fifth leading cause of death in the US, and in the UK it has just displaced heart attacks and stroke as the leading cause of death among women and the second-leading cause of death among men.3
Drugs make it worse
Besides the chilling numbers, there is deep disappointment in mainstream medicine's approach to the crisis. The gold standard of care at most brain clinics might be an MRI, a few blood tests to rule out other obvious conditions, some advice to watch out while driving and making financial transactions—and perhaps a word about looking into arrangements for long-term care.
An Alzheimer's diagnosis is typically followed by a prescription for a cholinesterase-inhibiting drug like donepezil (trade name Aricept) or the NMDA receptor-blocker memantine (trade names including Abixa, Dementa and Namenda), which affect how the neurotransmitters acetylcholine and glutamate work in the brain.
Not even after decades and billions spent on research can the drug makers make high claims about their products. They can't halt or slow the progression of Alzheimer's. While drug companies maintain that the drugs can "improve cognition and behavior," they have significant side-effects, too.
Donepezil can cause nausea and vomiting, peptic ulcers and gut bleeding, insomnia and bizarre dreams, muscle cramping, fatigue, anorexia and urinary tract infections. Memantine is a "dissociative anesthesia" with common side-effects that sound as bad as Alzheimer's itself: confusion, dizziness, drowsiness, headache, insomnia, agitation and hallucinations.
"Not only has not a single drug worked to stop Alzheimer's progression, let alone to reverse it in patients, there's actually evidence that the top drugs may make patients decline faster," internationally recognized neurodegenerative disease researcher Dale Bredesen of the University of California, Los Angeles, told WDDTY.
The author of The End of Alzheimer's (Penguin Random House, 2017) pointed to a study published in November 2018, which looked at 2,714 patients in 10 studies who were receiving cholinesterase inhibitors, memantine or both types of drugs compared to the patients taking neither drug.4
When researchers from the University of Alabama at Birmingham and the Keck School of Medicine at the University of Southern California in Los Angeles pooled all the patient data and reanalyzed it, they discovered that people taking these widely prescribed Alzheimer's drugs had a "significantly greater annual rate of decline on the ADAS-cog [a measure of cognitive function in Alzheimer's disease] than those receiving neither medication." And patients receiving both types of drugs performed worse than those receiving only cholinesterase inhibitors.
100 points of light
All of this would make for very bad news for someone just diagnosed with Alzheimer's. Or even for those diagnosed with milder cognitive decline.
It would be bad news, except that there is now something far more promising than resignation or drugs on the table for those with either condition. Bredesen and 15 other researchers from clinics across the US and in Australia recently published a study describing 100 patients treated by a comprehensive, custom-fit protocol called ReCODE for the reversal of cognitive decline.
It's a multi-faceted attack on the disease using diet, lifestyle, detoxing, and addressing nutritional deficiencies and hormonal imbalances to impact key cellular mechanisms that Bredesen and his colleagues identified as underlying Alzheimer's progression.
Each of the 100 patients showed documented reversal of cognitive decline—in some cases with improvement on medical imaging and diagnostic tests as well as cognitive tests. Each has a different story and tailored treatment, but it is the common threads that make the protocol the most truly promising therapy for Alzheimer's since the condition was first described over a century ago.
Bredesen says he has treated more than 1,000 people with similar success at the Buck Institute. "Virtually 100 percent of the people we see with mild cognitive impairment benefit to some degree from the ReCODE program," said Bredesen. About half of those with more severe cognitive decline improve, but unfortunately, "among those in advanced stages of Alzheimer's, only a minority show improvement. That is why it is important to start early."
The brain's live-or-die switch
What Bredesen and his colleagues are doing differently than mainstream medicine is based on his more than three decades of studying neurodegenerative diseases in the laboratory.
While virtually all drug research and design has focused on the hallmark sticky amyloid plaques found in the brains of Alzheimer's patients, which are considered the culprits behind the disease, Bredesen was looking at the molecular level at what causes the plaques to form in the first place.
His work focused on a protein called amyloid precursor protein (APP), which acts as a sort of molecular switch that sends one of only two signals to neurons in the brain: a "stay healthy" signal that nourishes the neurons and maintains the connections between them, or a "suicide" signal that kicks off chemical events telling the cell to die.
The suicide signal can be tripped when APP connects with the amyloid-beta protein that makes up those nasty plaques in the Alzheimer's brain. It also happens that when the suicide switch is flipped, more amyloid-beta protein is produced, and a slow chain reaction of neuron death and amyloid buildup begins to spiral as Alzheimer's progresses.
The disease itself, Bredesen and his colleague Alexei Kurakin have argued, is "not inherently pathological." It is rather like the brain's top financial officer has noticed a deficit of resources on the books, and he's begun executing a ruthless downsizing program, slashing the least important jobs and preserving only the critical positions to keep the company afloat.
"[I]t is pulling back, preserving only the functions it needs to stay alive, and not expending energy or resources on the formation of memories it doesn't need," Bredesen explained in his book. "Given a choice between remembering how to speak (or breathe or regulate your body temperature) and remembering what happened on the 'Friends' rerun last night, your brain opts for the former."
Off or on?
Bredesen's team then started looking for things that flip this molecular APP switch from "stay healthy" to "die," but rather than one critical factor they found a laundry list of critical influencers. They've pared the list down to 36 factors, including estrogen and testosterone, thyroid hormone and insulin, vitamin D, specific inflammatory molecules from a fired-up immune system, the presence of toxins like metals and genes that favor the death pathway.
It turns out that all of these factors match up very well with a wide range of seemingly disconnected studies that have linked Alzheimer's to everything from gene mutations like the ApoE4 allele to exposure to toxic metals, herpes infection, use of statin drugs, insulin resistance and diabetes, high blood pressure, low kidney function, sedentary lifestyle, lack of sun, sleep deprivation and chronic stress.
Big Pharma has been searching fruitlessly for a silver bullet to destroy Alzheimer's plaques, but it's missing a much bigger picture. Amyloid plaques are a byproduct of the disease in Bredesen's model, not its root cause, but all these wide-ranging factors linked to Alzheimer's trip the same switch.
The factors driving the disease may seem to vary wildly from one person to the next, but underlying them all is this APP mechanism, which acts like a seesaw that can be tipped into or out of disease, depending on the number of factors that favor either health or degeneration. In short, all sorts of choices you make daily become either pro-Alzheimer's or anti-Alzheimer's, and you have the power to tip the scale.
The bigger picture
Bredesen had a personal experience that must have impacted his way of looking at disease. When his teenage daughter was diagnosed with early-stage lupus erythematosus, an autoimmune disease that is a leading killer of young women, he and his wife, also a doctor, took her to see top specialists.
"They suggested steroids to turn down the immune system, but they told us that she was at high risk of chronic, severe lupus and there was no other treatment," he says. "Nobody even asked what was causing the disease. It was shocking."
The family stepped out of the box of mainstream medicine and turned to integrative medicine, which had much more to offer—diet changes to exclude inflammatory agents like gluten and dairy, deficiencies to be tackled and hormones to balance.
Over the following months, they watched as their daughter's rashes, amenorrhea, joint pain and other symptoms disappeared. A decade later, she is still asymptomatic. Bredesen saw how disease can be dialed up or down in the body by simultaneously controlling multiple factors like diet and stress.
Parallels in health
The ReCODE protocol overlaps with the advice of many leading alternative practitioners including optimal health guru Joseph Mercola (see accompanying story, page 44); Mark Hyman of the Cleveland Clinic, who treats a range of inflammatory conditions by diet and lifestyle; and neurologist David Perlmutter, author of Grain Brain (Little, Brown and Company, 2013) (see box, page 33).
Bredesen begins by advising that every person over age 45 should get a 'cognoscopy' (see box, page 37)—a range of diagnostic lab tests, imaging and a baseline assessment of cognitive function.
Those results are then compared to a database to identify patterns and tailor an individualized therapy program for each patient.
Bredesen says Alzheimer's patients need to be treated like competitive athletes, not simply skimming within 'normal ranges' of brain health markers, but optimizing them and measuring them the way we measure blood pressure.
Rather than waiting for mainstream medicine to jump on board, he has begun training hundreds of physicians in the ReCODE protocol via his company, Apollo Health New Practices.
In Bredesen's experience, there are three main types of Alzheimer's disease, each with relatively distinct symptoms:
Type 1. Primarily inflammatory, from a fired-up immune system
Type 2. Primarily deficient in key nutrients like vitamins, minerals and hormones that support brain health
Type 3. Primarily toxic, reacting to foreign substances like metals or biotoxins such as from mold.
Each subtype influences the APP/amyloid-beta spiral, and each has its own treatment, but there is overlap. The protocol draws from integrative and functional medicine, Chinese and Ayurvedic practices, and other fields.
Asked what can be done for those already lost deep in Alzheimer's today, like Jean Wilson, Bredesen's answer is revealing and sad. "Their children should get genetic testing, find out where they stand and start on a program early," he said. It's rare to find someone who pulls out of Alzheimer's if they're already long gone.
Still, even patients with marked cognitive decline can see results. One of Bredesen's patients, Edward, is a successful businessman whose case stands out because doctors had documented his decline with repeated PET scans and cognition tests, and he carried a genetic marker for Alzheimer's risk.
At age 60, he started noticing increased memory problems, forgetting people he had met and struggling with once-easy calculations. Ten years of medical scans revealed a declining pattern typical of early Alzheimer's, and at age 67 his neuropsychologist suggested he wind down the business and start seeking long-term care.
He went to Bredesen instead, and after just a few months on a concierge ReCODE program, Edward started to notice big improvements. Two years later, he decided to repeat the neuropsychological evaluation he had undergone previously.
Bredesen remembers the call from the examiner—the same one who had seen Edward before. He said that in 30 years, he had never seen such improvements. Edward's verbal learning scores had shot from the third percentile to the 84th percentile. His auditory memory had improved from the 13th to the 79th percentile, his reverse digit span from the 24th to the 74th percentile and his processing speed from the 93rd to 98th.
Edward is still in business. As he told Bredesen, "I have allowed myself to think of the future once again when I talk to my grandchildren."
Switching on the brain
Here are just a few of the 100 patients that made up Bredesen's documented success stories:
A 68-year-old professional woman began to make obvious slips in her speech and spelling. On medication for depression, she also began to have difficulty with everyday tasks such as shopping, cooking and computer work. Even making a gingerbread man became a struggle. She confused the minute hand and hour hand on a clock, and she forgot to pick up her grandchildren at school twice in two weeks.
Genetic testing found she had one copy of the ApoE4 allele, carried by 75 million Americans.
These people have a 30 percent chance of developing Alzheimer's disease, compared to 9 percent for people who don't have the allele. Those with two copies have a 50 percent chance of developing the disease.
An MRI scan showed that the hippocampal region of her brain had shrunk to a volume in the 14th percentile for her age.
Diagnosed with mild cognitive impairment (MCI), she grew worse after each trial of a new antibody treatment and stopped, then tried ReCODE.
Over the next 17 months, her test results on the Montreal Cognitive Assessment increased from 24 to the highest score of 30 and remained stable for 18 months.
Her hippocampal volume increased to the 28th percentile. Her symptoms improved, as did her daily task performance, and all remained stable on follow-up.
A 73-year-old doctor said her struggle to find the correct words for things had begun insidiously nearly 20 years earlier, but it had worsened significantly over the past year.
She could not remember recent conversations, plays she had seen or books she had read, and she mixed up the names of people and pets. She had trouble navigating, even finding her way back to her restaurant table after using the restroom.
A PET scan of her brain revealed problems using glucose as fuel. An MRI revealed atrophy of the cortex (a recognized feature of Alzheimer's) and decreased hippocampal volume (16th percentile for her age). Online cognitive testing placed her at the 9th percentile for her age.
Over the course of a year on the ReCODE protocol, her memory improved, and her online cognitive assessment shot to the 97th percentile and stayed there for the rest of the study.
A 62-year-old woman experiencing fatigue, depression and poor sleep had lost the ability to remember names, do the accounting she had done previously and run her business.
Her ReCODE protocol included bio-identical hormone replacement, restoring insulin sensitivity through specific diet changes, regular exercise and stress reduction, enhancing her microbiome with probiotics and prebiotics, reducing systemic inflammation with omega-3 fats, and increasing vitamin D, vitamin K2 and other vitamins as well as brain training.
Over the next 12 months, she lost weight, her metabolic status improved and her symptoms resolved too, so she reopened her business. Her cognitive assessment score rose from 20 to 28 (26 to 30 being normal)—and stayed there.
Increasingly, integrative practitioners like Dr Joseph Mercola have protocols with features in common with ReCODE, including:
• a diet low in carbohydrates and high in healthy fats like omega-3 oils
• low sugar consumption
• elimination of processed foods, including their damaging oils
• elimination of immune-stoking foods like gluten
• regular, intense exercise
• optimized vitamin D levels
• optimized sleep
• stress reduction and management.
The ReCODE protocol
Here are the highlights of the ReCODE protocol:
Ketogenic diet. Researchers from the Mayo Clinic published research in 2012 showing that people whose diet is mostly carbohydrates (pasta, rice, potatoes, bread, muffins, etc.) have an 89 percent increased risk for either mild cognitive impairment or full-blown dementia. In contrast, those consuming the highest levels of fat had a 44 percent reduced risk.1
When your body is running low on carbohydrates, it burns fat instead. The liver metabolizes fats into compounds called ketone bodies, and this process, called ketosis, is good for brain function.
ReCODE utilizes the Ketoflex 12/3 diet, also called the flexitarian diet, which is high in raw and cooked non-starchy vegetables, includes meat and small, low-mercury fish as a "condiment," and contains lots of good fats from nuts, avocados, seeds, and coconut or MCT (medium-chain triglyceride) oil.
Turning off digestion has many benefits for the brain, including inducing autophagy, in which cells clear themselves of toxins and carry out repair work.
The '12/3' in the Ketoflex diet refers to the 12 hours you should leave between your last meal at the end of one day and your first snack or meal the next day, and the three hours you should maintain between your last meal and going to bed.
So, if you go to bed at 10pm, don't eat after 7pm, and hold off on breakfast until at least 7am the next day.
ReCODE recommends vitamin B1 (50 mg), which is important in memory formation, pantothenic acid (100-200 mg) for alertness, a vitamin B6/B12/folate combination, vitamin D (2,500 IU per day until optimal levels are reached), vitamin K2 as MK7 (100 mcg), citicoline (250 mg twice a day) for synapse growth and repair, and ubiquinol, or coenzyme Q10 (100 mg), to support the cells' powerhouses, the mitochondria.
Ashwagandha, sometimes called Indian ginseng, is a traditional Ayurvedic nerve "tonic."
Suggested daily dosage: 500 mg twice per day to reduce amyloid and combat stress
Gotu kola is an Asian medicinal herb that can promote wound healing and help with venous insufficiency—where blood pools in the veins rather than flowing through them—as well as increase alertness and focus.2
Suggested daily dosage: 500 mg twice per day
Rhodolia extract has been shown to be effective at reducing anxiety and stress.3
Suggested daily dosage: 200 mg once or twice a day, for those who are anxious
The ReCODE protocol has teamed up with neuroscientist Michael Merzenich, founder of Posit Science, which makes Brain HQ (www.brainhq.com).
This online system uses games like Double Decision and Hawkeye, which are designed to improve brain processing time by practicing 10 to 20 minutes a day or 30 minutes three times a week.
How to test whether you are at risk
A cognoscopy consists of a collection of blood tests, imaging and cognitive assessments that Dale Bredesen uses to measure the levels of bodily systems that, when abnormal, can contribute to cognitive decline.
Genetics. The test for the ApoE4 gene allele gives an idea of your relative risk of getting Alzheimer's in your lifetime. If you are ApoE4 negative, your chances are about 9 percent. Carry one allele and you are among the 75 million Americans with about a 30 percent risk of the disease.
Pregnenolone is a master steroid hormone from which other sex and stress hormones are derived, and it is frequently found to be low in women with cognitive decline. Ideal levels: 50 to 100 ng/dL.
Mainstream doctors often only test for thyroid stimulating hormone (TSH) and don't check other thyroid hormone levels including free T3, free T4 and reverse T3.
TSH should be under 2.0 microIU/mL. Free T3 should be 3.2-4.2 pg/mL, and reverse T3 below 20 ng/dL. The ratio of free T3 (×100) to reverse T3 should be over 20. Free T4 should fall between 1.3 and 1.8 ng/dL.
Magnesium levels. The most accurate test is the red blood cell magnesium level, which should fall between 5.2 and 6.5 mg/dL.
Brain volumes. MRI scans can identify areas of shrinkage.
Cognitive assessment tests, to score your brain's function at various tasks. The Montreal Cognitive Assessment (MoCA) is free online (www.mocatest.org) and takes under 10 minutes to do.
Dale Bredesen MD,
Apollo Health New Practices:
David Perlmutter MD: