Is it possible to reverse Alzheimer’s?

https://www.thetimes.co.uk/article/is-it-possible-to-reverse-alzheimers-wvdk9scpp

As the frazzled mother of four children under ten, Eleanor Smith didn’t think it was significant when she couldn’t recognise her children’s friends at the school gates. Then, when she started mixing up actors’ faces and couldn’t follow plotlines any more, she put it down to middle-aged absent-mindedness.

As a former lawyer who had become heavily involved in charity work, Smith, then 40, was used to operating under high levels of stress and keeping several plates spinning simultaneously. Yet what she had dismissed as the effects of stress were in fact the first signs of Alzheimer’s dementia, a disease that afflicts about 1 in 14 people over the age of 65 and, unless a miracle treatment emerges, will incapacitate two million people in Britain by 2050.

Smith, from New Jersey, is one of 1,000 people who have signed up to ReCODE, a radical programme that claims to reverse Alzheimer’s disease and restore mental sharpness by getting participants to undergo a lifestyle overhaul. “It is really shocking to reflect on how I was,” Smith says. “I started feeling really tired in the afternoons, I didn’t participate in board meetings, I felt that I couldn’t follow complex arguments. My vocabulary seemed to be shrinking and I would forget what I was saying halfway through a sentence.” Yet within four months of beginning ReCODE her “brain fog” had vanished

The protocol has so far been the subject of only one successful published scientific study involving ten patients. Yet up to 100 times as many are now using ReCODE, which its author, Dr Dale Bredesen, details in his new book, The End of Alzheimer’s. The American neurologist is in talks with Cleveland Clinic in Ohio and the hospital provider Providence Health to conduct trials involving 150 patients to compare the effects of ReCODE with Aricept, the standard drug given to those with early stage Alzheimer’s. Bredesen, who is a professor of neurology at the University of California in Los Angeles, is confident that his system can show complete reversal of early stage mental decline in a matter of months.

The main principle of Bredesen’s theory is that amyloid plaques, the sticky connection-blocking gunge identified by Aloysius Alzheimer when he first described the brain condition in 1906, are not the cause of dementia, but a symptom of the brain’s unsuccessful efforts to repair itself.

His regimen involves up to 150 markers, including blood tests and questions about medical history, exposure to anaesthetics and environmental factors. The results are then processed by the ReCODE computer algorithm (the patented element of intellectual property in the programme), which produces an individualised set of supplements and other strategies to reverse the onset of memory loss. Making these changes, Bredesen says, fosters the natural elimination of amyloid plaques and the restoration of healthy brain function.

More than 450 doctors, nurses, neuropsychologists and nutritionists have been trained in how to deliver it, and Bredesen says that 12 UK doctors have shown interest in administering ReCODE. It is due to become more widely available in Britain after a doctors’ training programme next year.

“Alzheimer’s is what happens when the brain tries to protect itself from three threats: inflammation caused by poor diet or disease; a shortage of supportive nutrients; or toxins such as metals or moulds,” says Bredesen, who has co-authored 225 pieces of published research in his career. “We now know that an extensive network of molecular interactions is involved in the development of Alzheimer’s, so a broader-based approach is bound to be more effective, and we do know people get better on this programme.”

Initial costs for the diagnosis and the prescribed anti-Alzheimer’s regimen are about £1,000, with annual maintenance costs for a battery of dozens of dietary supplements averaging a similar amount.

For Smith the benefits far outweigh the cost. She recalls the disease taking hold in a way that was “very slow, gradual and insidious”. The low point came “when I was helping a friend run a baked goods stall at a fundraising event. People kept coming up to greet me using my name and I had no idea who they were. I had to go and busy myself in the background because it was so embarrassing.”

It was only nine years later, when she was 49 and heard a radio programme discussing prosopagnosia (the inability to recognise people’s faces) and its connection with other symptoms of Alzheimer’s, that Smith started to realise that something was badly wrong.

Her grandmother died of Alzheimer’s aged 70, and her 78-year-old father — who lives near by — also has advanced dementia. He is no longer able to recognise his family. “I decided to get myself tested for genetic susceptibility, which I just hadn’t dared to do earlier because there was no treatment,” Smith says.

Genetic profiling, which costs about £100, has taken off in a big way in America, with thousands wanting to know if they have an increased inherited risk of conditions that have killed loved ones so that they can modify their lifestyles accordingly.

Smith was tested for variations of the apolipoprotein E (ApoE) gene, which is crucial for organising the transport of cholesterol and other fats found in high concentrations in the brain (these are vital for the function of brain synapses or connections). ApoE4 is associated with increased risk of Alzheimer’s. Experts and the British Alzheimer’s Society agree that carriers of one ApoE4 copy may have twice the risk of developing dementia and that for carriers of two copies the risk increases four or five times. Smith was devastated to discover that she had one ApoE4 copy.

“The gene clinic didn’t give me any help. They just told me to eat healthily and exercise, and come back in six months to see if they could get me on a drug trial. I had the testing because I thought I could prevent the problem, not to be told that it was already too late and I was in trouble.”

A relative had read some of Bredesen’s work and suggested she give ReCODE a try. Local doctors put her through the tests and, four months down the line, Smith’s touch-typing speed rocketed, she regained the ability to sight-read music and her vocabulary expanded well beyond its previous limits.

However, Bredesen’s regimen is not for the faint-hearted. He says that there are 36 different mechanisms contributing to Alzheimer’s progression and all have to be tackled separately. One of the 36 requirements is the stimulation of ketone production (which produces a pear-drop smell on the breath) when the body begins to break down fat stores because food is not being supplied. Bredesen says this state is beneficial for the brain and everyone should have an overnight food-free period of at least ten hours in each 24-hour day, including no snacking for three hours between dinner and bedtime. He even recommends that people buy ketone meters, which measure levels in blood, urine or breath, to check that they are doing it correctly.

Smith, who is now 51, takes an extraordinary personalised daily cocktail of more than 30 supplements, each designed to improve the function of specific receptors in her brain. She religiously exercises for 30 minutes six days out of seven, eats little or no processed food and ensures that she fasts according to Bredesen’s stipulations. She uses melatonin and magnesium to ensure that she sleeps for seven to eight hours every night to maximise “brain detox”.

Other Bredesen patients show similar discipline and enthusiasm, though the stigma of dementia remains. Many of the case studies in the book — Smith included — refuse to be identified for fear it will damage their personal or professional prospects.

That is not the case for Julie Gregory, 55, a therapist from Indiana who runs a global support network for ApoE4 carriers. Like Smith, she carries one copy of the rogue ApoE4 gene and also started noticing brain-processing problems in her forties. She follows a similarly rigorous health-management programme, but believes it is worth it. “ReCODE has transformed my life,” she says. “My cognitive performance was in the bottom third for my age group; now I am in the top 10 per cent according to the tests.”

Sally Weinrich, a senior academic nurse from South Carolina, says she knew she had an increased risk of developing dementia because the condition has affected a large number of her close relations. When she started to notice her own cognitive impairment the 76-year-old got in touch with Bredesen and asked a local physician to measure the different indicators set out in ReCODE. “The interesting thing about this is that as soon as you stop taking the treatment you notice your cognitive function start to decline within a few days,” she says. “It really works.” She has been on the programme for nearly three years.

“We are looking for people to actually get better on this protocol and stay better,” Bredesen says. “If you have signs of cognitive decline in your forties or fifties and sixties, 20 years before you get Alzheimer’s, that’s when we can do something about it.

“Our longest patients have been on this for more than five years. One patient has gone off it four times for various reasons and each time she has rapidly regressed.”

British authorities remain sceptical. “There’s no firm evidence that this type of intensive lifestyle regime can ‘reverse’ Alzheimer’s disease, so the way this approach is being marketed is concerning,” says Doug Brown, the research director at the Alzheimer’s Society. “The research published so far involves just ten people with memory impairments and only half of them would meet the criteria for being diagnosed with Alzheimer’s disease. It’s therefore impossible to determine which, if any, of the elements in this therapy can improve memory and thinking abilities in people in the early stages of dementia.

Karen Ritchie heads a European Alzheimer’s disease collaboration in France and is scientific adviser to the Alzheimer’s Research UK trust. She says that “dealing with some of these — diet, blood pressure, diabetes prevention, may push back dementia onset, but not reverse the disease process”.

Bredesen points out that of 244 potential Alzheimer’s drugs tested between 2000 and 2010, only one, Memantine, was approved by American and European regulators. However, Stephen Pearson, a psychiatrist who leads an Alzheimer’s drug trial unit in Plymouth, is unmoved. “Bredesen has done important research, but I struggle with his claim to have found a cure. Effective treatment will come from a drug and I’m optimistic that we will have one in five to ten years’ time.”

Either way, Bredesen is pressing on. “Dramatic reductions in the prevalence of dementia could be achieved if more people underwent genetic testing to determine their ApoE status and initiated a preventive programme long before any symptoms appeared,” he says. “We want people to remain mentally sharp, then be acutely ill only for a few seconds at the end of their life before they die. We don’t want them to suffer this grim descent into a mental abyss.”
Some names have been changed

The End of Alzheimer’s by Dr Dale Bredesen is published by Penguin, £14.99