By JEROME BURNE, AWARD-WINNING MEDICAL JOURNALIST
It is over 20 years since I discovered in my fifties that I have a copy of the gene, ApoE4, that’s been linked to a raised risk of Alzheimer’s.
It’s the same gene that the actor Chris Hemsworth carries, although he has two copies, one from each of his parents – he learned this in 2022 after having tests for a documentary series he was making about longevity.
Now comes news of a major study that’s found that almost everyone who has two copies of this gene goes on to develop early signs of Alzheimer’s – researchers at the Sant Pau Research Institute in Barcelona looked at data from 10,000 people and 3,000 brain donors and found that the majority of those with two copies showed signs of Alzheimer’s by the time they reached the age of 55. The researchers estimate that around 2 per cent of people have this gene profile
My ApoE4 Gene
My ApoE4 gene was identified when I was writing about the gene tests then just becoming publicly available, and as a health journalist I took one. It was an alarming discovery, since not only do I have no family history of Alzheimer’s, but back then there was nothing to be done about it, and for a while, common moments such as forgetting why I was peering into the fridge or a cupboard felt like a sinister warning.
But I quickly persuaded myself that any brain malfunction wouldn’t begin for years. Anyway, a cure might come along any time and as a health journalist I could keep up with the latest research.
Yet for years there was little to be hopeful about – the few drugs that were available didn’t make a difference to the disease progression.
Small bits of cutting-edge research I came across here and there convinced me to try various lifestyle approaches (more on the specifics later), but the expectation has long been that once you’re heading into the medical territory that is Alzheimer’s, you need heavyweight pharmaceuticals.
New Developments in Alzheimer’s Prevention
But the cheering, and very surprising news, is that nutritional and lifestyle advice, with some additions and tweaks, is the very latest thing in Alzheimer’s prevention, with several UK charities and academic centres – including Imperial College, London, Exeter University, and Alzheimer’s Research UK – now actively investigating lifestyle.
What’s driving this dramatic U-turn is the failure of the drug industry to come up with effective and safe products. Even the newer ‘wonder’ drugs such as donanemab and lecanemab, which can delay the worsening of the disease by around a third in patients, can have serious side-effects – around a quarter of those who take them suffer bleeding or swelling in the brain, and some patients have experienced brain shrinkage.
These drugs work by clearing the brain of amyloid plaques, the sticky proteinProteins are large molecules consisting of chains of amino acids. Proteins are essential nutrients for the human body – they are a building block of… deposits thought to cause symptoms by disrupting communication between brain cells.
The problems with the latest drugs are detailed in a new book by leading neurologist Professor Karl Herrup, of Philadelphia University. In ‘How not to study a disease: The story of Alzheimer’s’ he writes: ‘In our rush to find a cure we have gone down a blind alley. For decades we have focused more on salesmanship than scholarship. The amyloid cascade hypothesis has become a steamroller, intent on crushing any alternative models.’
One problem is that having the plaque doesn’t necessarily mean you will have Alzheimer’s, and not having it doesn’t mean you won’t.
As Professor Herrup points out, ‘we need to rebalance this amyloidhypothesis about the cause of Alzheimer’s’ to include ‘other worthy ideas about its nature, such as those indicated by the links with diabetes and blood vessel damage and the insights gained from approaches involving diet, nutrition, and lifestyle’.
Improving the Health of Body Systems to Protect the Brain
What’s so radical about the nutritional and lifestyle approach is that it doesn’t target a single cause but aims to improve the health of many of the body’s systems – such as metabolismMetabolism is a term that is used to describe the chemical reactions that take place within the body’s cells. The body gets the energy it… (how energy is used), the immune system and the vast colony of bacteria and other microbes (the microbiome) in your guts, that have a two-way connection with the brain. Keeping them all healthy can do the same for the brain.
And it means we can all take steps to protect themselves, which is what I’ve tried to do.
I spoke to Tommy Woods, an Assistant Professor of neuroscience and paediatrics at the University of Washington, who is a principle investigator for the research charity, the Food for the Brain Foundation (foodforthebrain.org), which is looking at dementia amongst other brain disorders. The charity offers a free online test to both measure your cognitive function but also a questionnaire that works out your risk. I did the test and it showed me exactly what, in my diet and lifestyle, was driving my risk.
He told me: ‘I first came across the idea of multiple approaches to health and fitness when I worked with athletes as a performance consultant. Many of the systems that affected their cognitive and physical abilities were the same as the ones we concentrate on at the charity with much older people.’
Low Blood Sugar Levels to Protect the Brain
Robert Lustig, who is professor emeritus and an international expert on metabolism, based at the University of California San Francisco, explains why both blood sugar levels and insulinInsulin is a hormone made by the pancreas. It is responsible for making the body’s cells absorb glucose (sugar) from the blood…. need to be kept at a low level to protect the brain.
Insulin’s job is to help the body use blood sugar (glucose) as fuel to clear it away into storage as fatThere are many different types of fats; polyunsaturated, monounsaturated, hydrogenated, saturated and trans fat. The body requires good fats (polyunsaturated and monounsaturated) in order to…. Professor Lustig, who is also advising the Food for Brain Foundation, says high levels of glucose – from a high carb diet – lead to higher levels of insulin. ‘Fairly soon, however, your system stops responding to insulin – known as insulin resistance – which is bad news because insulin delivers the glucose needed for energy in the brain and muscles.’
Going Low GL
This is the kind of information that convinced me over the years to make changes to my diet. The standard advice to have plenty of carbs and pick the low-fat option was reversed, and I started following a ketogenic diet that involves eating much more fat, mostly saturated and is very low in carbs.
The fat gets turned into small packets of energy, known as ketones, that can power brain cells.
I also started stepping up gym visits from a couple of times a week, to three or four. Exercise improves blood circulation which is needed to clear waste products from the brain.
The Gut and the Brain
I started paying attention to my microbiome, the colony of microbes that lives in the gut. This involved eating more fibrous vegetables, as well as making and drinking kefir, a fermented drink that delivers probiotics to the guts, every day.
B Vitamins
And I started taking B vitamins.
A decade after my gene was spotted, a randomised trial at Oxford University, run by Professor Emeritus David Smith, showed that B vitamins were essential for clearing a toxic compound called homocysteineHomocysteine is an amino acid found in the blood. Elevated levels of homocysteine have been associated with narrowing and hardening of the arteries, an increased… from blood.
Homocysteine comes from the breakdown of proteins, and can damage cells. High levels are often found in the brains of Alzheimer’s patients.
In the Oxford study, which involved over 200 people with mild cognitive impairment (MCI) – where memory and clear thinking are impaired – half were given a daily high dose of a B vitamin, the rest a placebo. A proportion of each group had a brain scan at the beginning and end of the two-year trial.
The results, published in the journal PLOS One in September 2010, were impressive: those in the vitamin group not only had reduced homocysteine levels but brain shrinkage – the sign of brain cell death – was half that of those in the placebo group.
Rather than being welcomed, however, the trial set off a long running academic battle. Alzheimer’s charities, including one that contributed funding, ignored it.
Another study which found no benefit from B vitamins was published four years later, but it didn’t convince me. While the participants in the Oxford trial had mild cognitive impairment, those in the later trials did not. So I kept taking the tablets.
One senior academic who has picked up on this research is Professor Peter Garrard, a specialist in neurodegenerative diseases such as Alzheimer’s, at St George’s Hospital in London.
When his mother Sheila started losing words and describing things in roundabout ways at the age of 78, he put her on a daily dose of high strength B vitamins.
‘It was very encouraging that despite having had a brain scan that showed significant cell damage, she didn’t get any worse and then gradually started doing a lot better,’ says Professor Garrard. Sheila died at the age of 89. ‘We’ll never know how long she would have lived without the vitamins, but it must have made a difference that she stayed very fit and active.’
Professor Garrard told me that he’d been impressed by the B vitamin research done at Oxford and regarded claims that the vitamins had no benefit inaccurate. ‘I check all my patient’s homocysteine levels and give them B vitamins if they are over the healthy level,’ he says.
Evidence for the benefit of B vitamins continued to mount, including in 2020, a review published by Professor Jin-Tai Yu from Fudan University in Shanghai, China’s leading Alzheimer’s prevention expert. Published in Journal of Neurology, Neurosurgery and Psychiatry, this analysed the results of 153 randomised trials and concluded that: ‘Homocysteine- lowering treatment seems the most promising intervention for Alzheimer’s disease prevention. ’ (The homocysteine-lowing treatment reviewed involved using folic acidWhat it does: Critical during pregnancy for the development of a baby’s brain and nerves. Also essential for brain and nerve function. Needed for utilising… (B9), vitamin B12 and vitamin B6).
What Next?
As for me, I’m sanguine about the latest research about the ApoE4 gene: I’m currently feeling fit and well, thanks to a programme that seems a sensible way to stave off physical decline in general, and neurological decline in particular.
More Information
To take the FREE Cognition test visit foodforthebrain.org.
HOLFORDirect stock Patrick Holford’s range of supplements including supplements for brain health, optimum daily health and immunity, blood sugar balance and healthy digestion.
Now available the NEW The Brain Food Upgrade Pack containing HIGH STRENGTH levels of nutrients in daily blister strips in one pack – Connect (B Vitamins), Omega-3 (Fats) and Lecithin (Phospholipids), providing optimum support for the brain.
Find out more about Alzheimer’s and Dementia and Low GL.
Dig deep – Patrick Holford books – Upgrade Your Brain and the Low GL Diet Bible.
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