The single greatest genetic predictor of Alzheimer’s disease is the presence of the ApoE4 variant of the ApoE gene, carried by about one in five people. Having this contributes 4% to 6% of the absolute risk for Alzheimer’s disease.[i]
This is often exaggerated as a risk factor because, if a person is an Apoe4 carrier, and changes nothing, they have about a 20% greater chance of developing Alzheimer’s later in life than someone who doesn’t. This is called ‘relative risk’. It doesn’t mean, however, that someone with the ApoE4 gene has a 20% chance of developing Alzheimer’s. This is because, as an example, a person without the ApoE4 gene at a certain age might have a 4% chance of developing Alzheimer’s, while someone with the ApoE4 gene might have a 5% chance, so their risk has gone up by, in this example, 20%. In absolute terms, the risk would be increased by only 1%.
New Study in Nature Journal
The new study in Nature journal[ii] shows two things: the first is that most ApoE4 carriers show some of the biomarkers for developing Alzheimer’s later on, namely higher levels of toxic amyloid and -p-tau proteins. This is not surprising.
However, and this is key, quoting the paper “In the dementia stage, there were no differences in amyloid or tau despite earlier clinical and biomarker changes.” In other words, even these indicators of risk had vanished, or were no longer more prevalent in those ‘with’ vs ‘without’ this gene variant. This means that, even if you could lower levels of amyloid earlier in the disease process, this is highly unlikely to have any effect.
This so-called ‘Alzheimer’s gene’ can only exert effects via non-genetic mechanisms, and these mechanisms are often susceptible to modification – with a person’s nutrition having the most direct influence.
In other words, genes only tell us about susceptibilities, tendencies – they are not (at least in this case) determinative of whether one does or does not develop Alzheimer’s in his/her lifetime, because other factors can modify the effects of carrying the ApoE4 gene variant. A gene variant such as ApoE4, is more like a dimmer switch and can be ‘over-expressed’ or ‘down-regulated’, turned up or dimmed down by a variety of lifestyle factors.
The Effect of Lifestyle Factors with the ApoE4 Gene
The ApoE4 gene is downregulated by eating a low-glycemic load (GL) or low sugar diet or more ketogenic diet with specific Mediterranean-style food choices including fatty fish, cruciferous vegetables, olive oil, low alcohol consumption. Four supplemental nutrients have reasonably good evidence of blunting the effects of the ApoE4 variant. These are omega-3 DHADHA is short for Docosahexaenoic Acid. It is an essential omega-3 fatty acid found in fish such as salmon, mackerel and herring, and is often…, B vitamins (B2, B6, B12 and folate) and vitamin DWhat it does: Helps maintain strong and healthy bones by retaining calcium. Deficiency Signs: Joint pain or stiffness, backache, tooth decay, muscle cramps, hair loss….. [iii]
But what happens to risk if a person is well-nourished with these dietary factors already? A good example of this is a recent study in China, involving 29,072 people of which 20% had the ApoE4 gene.[iv] Each participant had their diet and lifestyle assessed over the 10 year period of the study to see who would or wouldn’t develop cognitive decline or dementia.
What the study showed was that whether or not a person had the ApoE4 ‘Alzheimer’s gene’ made no difference to the positive reduction in risk achievable by simple diet and lifestyle changes.
“These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors is associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors.
Diet and Nutrition the Most Important Prevention Step
Eating a healthy diet was also the most important prevention step, followed by an active lifestyle, with one’s intellectual life, then physical activity, then social interactions being the next most important steps.
Eating a healthy diet was about twice as important as exercise in predicting cognitive decline. Those with a healthy diet were about seven times less likely to have age-related cognitive decline or dementia than those with an ‘average’ diet and about nine times less likely to develop dementia than those with an unfavourable diet.
All major studies on people at risk of or already with dementia or Alzheimer’s have measured whether the study participants do or don’t have the ApoE4 variant. We’ve looked at the major studies that have measured the impact of a change in diet or nutrition or lifestyle and they almost all show no difference in outcome if you do or don’t have the gene.
Conclusion
A good analogy is that having the ApoE4 gene variant is like a weak beam of light which, in the darkness, increases one’s risk a bit, but once you shine the strong light of actually doing something such as changing your diet or supplementing omega-3 fish oils, B vitamins or vitamin D the effect of being an ApoE4 carrier seems to be invisible, in that there is no significant difference in outcome between those who had or didn’t have this gene variant.
Please note: the pharmaceutical industry is keen to promote a drug that lowers amyloid or p-tau. 14 trials have shown that anti-amyloid drugs do lower amyloid but none has had clinically significant effect on actual dementia or cognitive decline.[v] In other words the amyloid theory is bust. Amyloid is not a cause of Alzheimer’s – it’s a result. Raised toxic P-tau is a direct consequence of raised 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…, driven by a lack of B vitamins. Read my report the P-Tau Delusion. Lowering homocysteine with B vitamins, which is an established cause, lowers p-tau.
What Next? Upgrade your Brain AND Become a Citizen Scientist
Thanks to already well over 400,000 ‘citizen scientists we have, with the sword of digital technology, opened the oyster to uncover the true causes – all under your control – that are driving this terrible and unnecessary brain shrinkage.
Those citizen scientists have taken the time, often initially for personal interest, to discover their actual cognitive function, and completed a comprehensive questionnaire.
We hope to reach a million people around the world within a year or so making this the biggest prevention-focussed study of its kind.
Change is not going to come from the Government or the NHS. It is going to have to come from us, the people.
We ask you to take control of upgrading your brain and in the process become Citizen Scientists for better brain health for future generations.
Follow these seven steps.
STEP 1: Take the Cognitive Function Test
What you’ll learn:
- Find out where you are on the cognitive function scale
- Learn the most important dietary and lifestyle actions you can take
- Take control of your mental wellbeing
- Contribute to the Food for the Brain research process
Take the Cognitive Function Test
STEP 2: Test for the Four Keystone Biochemical Processes
A consensus of world experts concluded that lowering homocysteine with B vitamins is the easiest and most cost effective prevention action, which Oxford University’s health economists estimate would save the UK £66 million per year.However, it’s vital to test both homocysteine and Omega-3 levels, as they are co-dependent. Homocysteine-lowering B vitamins only work in those with sufficient omega-3, and omega-3 only works if homocysteine is low.
So, get tested for the four keystone biochemical processes with the DRIfT Test.
It will calculate your Dementia Risk Index functional Test (DRIfT) score. Tracking this, along with your Cognitive Function (CFT) and Dementia Risk Index (DRI) is the most comprehensive way to protect your brain.
This 4-in-1 test measures:
- Vitamin D
- Omega-3
- Homocysteine
- HbA1C
More info – Drift Test from Food for the Brain and Other Tests.
STEP 3 – Get Educated
Read my book Upgrade Your Brain – Out Now!
More info & to order – Upgrade Your Brain Book
Join me on my UK or Ireland Seminar Tour – May/June
I’m visiting 30 cities in the UK and Ireland in May/June to kick start a nationwide ‘Upgrade Your Brain’ campaign.
“We need to engage with millions of people, get nutrition education happening in schools, and most of all get heath authorities and governments around the world to take the mental health meltdown seriously and put brain health at the top of the health agenda.”
Professor Crawford says “Today’s diet bears no resemblance to the wild foods we ate during our species’ evolution to which our genome is adapted. If we don’t prioritise brain health and nutrition the continued escalation of mental ill health, starting in the 1950s, can only end in disaster.”
Dates/locations: More tour info & how to book
Sign up to my E-News
Go to the home page of this website and sign up to my E-News for more blogs/reports/videos and podcasts on brain health. Follow on Facebook (PatrickHolford) and Instagram. (PatrickHolford.UK)
STEP 4: Start a Brain Healthy Diet
The Upgrade Your Brain cooking app with brain-friendly recipes will be launching soon. It will help you make the right food choices for your brain.
STEP 5: Ensure You Get Enough of the Right Nutrients
There are three essentials for building brain cells (neurons) – omega-3 fats, B vitamins and Phospholipids. Omega-3 is bound to phospholipids by methylationMethylation is what occurs when the body takes one substance and turns it into another, so that it can be detoxified and excreted from the… which is a process that is dependent on B vitamins – B6, B12 and folate.
There are some key supplements that have been identified to support brain health. In the Holford range these are:
- Connect: B vitamins and zincWhat it does: Component of over 200 enzymes in the body, essential for growth, important for healing, controls hormones, aids ability to cope with stress… to support healthy methylation
- High PC Lecithin – A Rich source of 63% phospholipid
- Omega-3 Support – 550mg of DHA and 750mg of EPAEPA is short for Eicosapentaenoic Acid. It is an essential omega-3 fatty acid found in fish such as salmon, mackerel and herring, and is often…
All these are found in the Brain Food Upgrade pack
STEP 6: Spread the Word & Promote Prevention
We urge everyone to share the ‘prevention’ message with others.
You can do this by sharing social media posts and blogs/reports.
You can participate in Alzheimer’s Prevention Day on 15 May and encourage others to do the same. Take the free 3-minute online Alzheimer’s Prevention Check and get motivated to make the eight brain-friendly diet and lifestyle changes
“You are the architect of your own brain’s future health.” says neurologist Dr David Perlmutter.
Take the test for Alzheimer’s Prevention Day
Step 7: Support the ‘Prevention’ Work
‘Friends’ donate £50 a year and get so much in return. This is how we are funding our amazing research team (see foodforthebrain.org/researchteam/). We are a lean, keen, small but mighty team.
Every donation, big or small, goes right back into helping people prevent these preventable and terrible diseases such as dementia. Together, we can change the world. We need to, because time is running out. We will lose our humanity if we don’t stop this brain drain.”
All donations are put back into research, and the results of the research are shared back to people.
Give to Food for the Brain and support their work.
References
[i] Heininger, K. (2000), A unifying hypothesis of Alzheimer’s disease. III. Risk factors. Hum. Psychopharmacol. Clin. Exp., 15: 1-70. https://doi.org/10.1002/(SICI)1099-1077(200001)15:1<1::AID-HUP153>3.0.CO;2-1; see also Ridge PG, Mukherjee S, Crane PK, Kauwe JSK, (2013) Alzheimer’s Disease: Analyzing the Missing Heritability. PLoS ONE 8(11): e79771. doi: 10.1371/journal.pone.0079771
[ii] https://www.nature.com/articles/s41591-024-02931-w.pdf
[iii] Norwitz,N.G.;Saif,N.; Ariza, I.E.; Isaacson, R.S. Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients 2021, 13, 1362. https://doi.org/10.3390/ nu13041362
[iv] Jia J, Zhao T, Liu Z et al., Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study BMJ 2023;380:e072691 http://dx.doi.org/10.1136/ bmj-2022-072691
[v] https://www.bmj.com/content/372/bmj.n156/rr
Comments
Join the Conversation on our Facebook Page