A hugely significant study in the British Medical Journal into age-related cognitive decline and dementia has stated that changing your diet and lifestyle from bad to good cuts your future risk of developing dementia by a massive nine times [1]

The study shows, significantly, that whether or not you inherit the ApoE4 ‘Alzheimer’s gene’ that one in five people carry, it makes no difference to the positive reduction in risk achievable by simple diet and lifestyle changes [2].

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.

This study, published on 25th January 2023, followed over 30,000 people over a decade and found that 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.

The assessment of a healthy diet was based on intake of fish, eggs, fruits, vegetables, legumes, nuts and tea, among other foods known to predict lower risk.

Increasing evidence that Alzheimer’s and Dementia are preventable

“These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors are associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors.

This study has been warmly welcomed by charity Food for the Brain, as it backs up their own research and the work they have been actively carrying out for 10  years, to help people reduce their risk of age-related cognitive decline.

Food for the Brain offers a free online assessment of a participant’s diet and lifestyle, called the Dementia Risk Index, which works out a person’s overall risk. The assessment also includes a cognitive function test to assess your memory. This charitable ‘citizen science’ action group have also just launched COGNITION, an interactive, personalised ‘brain upgrade’ programme that then shows you, week-by-week, how to make positive changes to bring your risk closer to zero.

Indeed, the on-line test assesses all the same risk factors the British Medical Journal study has shown impact a person’s future risk – diet, active physical, intellectual, social lifestyle, smoking and drinking habits.  

According to Professor David Smith from the University of Oxford, one of the charity’s scientific advisors, “Genes can only exert effects via non-genetic mechanisms and these mechanisms are often susceptible to modification by, for example, improving one’s diet. This study shows that diet and lifestyle are much more important than inheriting a gene variant such as ApoE4. Less than 1% of Alzheimer’s is directly caused by genes. With no clinically effective drugs, and minimal role of genes, this study confirms that the focus must be on making diet and lifestyle changes that reduce risk of developing dementia, as foodforthebrain.org are doing. It also shows that switching from an average to a healthy lifestyle, with positive diet changes being key, can dramatically reduce a person’s future risk of developing cognitive decline and dementia.” 

Another member of the science team, Dr Celeste de Jager Loots, Research Associate at Imperial College’s  AGE Unit where she researches risk factors and prevention of Alzheimer’s and dementia, explains that “While having inherited certain genes can be used to predict risk of dementia, that risk is changed by making positive diet and lifestyle changes. The emphasis needs to be on changing diet and lifestyle, especially since one cannot change one’s genes. The earlier one starts with a healthy lifestyle the better the chance of preventing effects of genetic risk.”

Risk for dementia can be detected from the age of 35 and subtle changes, picked up by Food for the Brain’s cognitive function test, can be seen up to 40 years before a diagnosis. The charity wants anyone over 35 to take the test and start making positive diet and lifestyle changes. “The average person can cut their future risk by three quarters just by making simple diet and lifestyle changes.” says Patrick Holford, who is directing the Alzheimer’s prevention project. “This prevention approach, if we reach enough people, could cut cases of dementia in the UK by a third. That’s why we are urging everyone over 35 to tell everyone they know to take the free and scientifically – validated and free Cognitive Function Test. Alzheimer’s dementia, which accounts for the vast majority of dementia, is irreversible. But it is preventable, as this study shows.”

Two thousand people every month are joining this campaign, assessing and reducing their risk. Over 380,000 people have now taken the test.

References

Jia, J. et al. (2023) “Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective Cohort Study,” BMJ [Preprint]. Available at: https://doi.org/10.1136/bmj-2022-072691. [1]

The evidence that only 1% of Alzheimer’s is caused by genes is here: Bekris, L.M. et al. (2010) “Review article: Genetics of Alzheimer Disease,” Journal of Geriatric Psychiatry and Neurology, 23(4), pp. 213–227. Available at: https://doi.org/10.1177/0891988710383571. [2]

Useful links

The free Cognitive Function test and Dementia Risk Index assessment is accessed here: https://foodforthebrain.org.

For more information on the citizen science campaign see ‘Alzheimer’s is Preventable – A Manifesto for Change’.

Patrick Holford, founder of Food for the Brain and voluntary director of the Alzheimer’s Prevention Project and Jessica Ferrari-Wells, Chair of the Board of trustees are available for interview, as are members of the the Scientific Advisory Board are available for interview and comment. 

Neurons, that is brain and nerve cells, are primarily made out of what’s called ‘phosphorylated DHA’. That means the omega-3 fat DHA that is bound to a kind of fat called a phospholipid, as shown in the figure below. 

Seafood contains phosphorylated DHA but DHA supplements, whether derived from fish oil or algae, is not phosphorylated. Hence, it needs to be attached to phospholipids to work. This attachment is done by a B vitamin dependent process called methylation. 

There are several different kinds of phospholipids with strange names all starting with ‘phosphatidyl’ such as phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine.  To a large extent these can be made from phosphatidyl choline. As a group of nutrients they are classified as ‘semi-essential’ because we can make some, but not enough for optimal health and especially optimal brain health. 

As a consequence there are moves afoot to classify choline (which can be easily attached to the ‘phosphatidyl’ part) as an essential nutrient with a recommended intake. This has come about due to the growing evidence that insufficient choline in pregnancy leads to cognitive impairment and developmental delay. This is particularly important for vegans because, like the omega-3 fatty acid DHA, there’s not much choline in plant-based foods, but there is some in foods such as quinoa, soya, beans, nuts and broccoli.

Currently an adequate intake of choline is defined as between 400mg and 520mg a day, the latter for pregnant and breast-feeding women. This is based on how much choline you need for healthy fat metabolism, liver function and reducing homocysteine levels. You also need choline to process cholesterol in the liver and brain. As you’ll see in the figure above, cholesterol is a vital brain component. But these levels don’t take into account what’s being learnt about choline’s role in brain development.. A good estimate of optimum daily choline intake would be at least 500mg and maybe double this in pregnancy. 

Most important is choline’s role in building, and maintaining, a healthy brain. A pregnant woman’s intake defines the cognitive abilities of their child. Twenty years ago we knew that pregnant rats fed choline half way through their pregnancy have more connections between brain cells, plus improved learning ability and better memory recall. Now we know it’s true for babies with several recent trials showing similar results indicating that more choline in pregnancy enhances cognitive development.

An example of this is a study which gave women in their third trimester of pregnancy either 480mg of choline or almost double this – 930mg. They then tested the babies’ information processing speed at 4,7,10 and 13 months. Not only were the babies of the mothers given the higher dose faster but also the longer the mother had been given even the lower dose the faster were the child’s reactions. The authors concluded that “even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring ”. Seven years later, there will still memory advantages in the children whose mother had extra choline during pregnancy.

Babies are born with blood choline levels three times higher than their mother, illustrating how vital this nutrient is for building neuronal connections, which newborn babies do at a rate of up to a million new connections a second! An optimal intake for brain function is likely to be a lot higher than the 400 to 500mg recommended for adults, and higher still in pregnancy.

Since brain cells are made of a membrane containing choline (and other phospholipids) attached to the omega-3 fat DHA, without choline the omega-3 doesn’t work. The attaching of the two depends on methylation, a process that is dependent on B vitamins, especially B12, folate and B6. Choline helps methylation and healthy methylation, indicated by a low blood level of homocysteine, helps synthesize choline. You need all three – DHA, choline and B vitamins especially B12. So, if you are lacking in DHA, or in vitamin B12, then you’ll be doubly dependent on getting enough choline.

Choline rich foods – are vegans at risk of deficiency? 

While the richest dietary sources are fish, eggs and organ meats there is significant amounts of choline in plant-based foods, notably soya as in tofu and soya milk, quinoa, nuts and seeds including flax seeds, almonds and peanuts, and cruciferous vegetables including broccoli, cauliflower and Brussels sprouts.

While, on the face of it, it does appear than vegans, especially those planning pregnancy, need to become choline focused in relation to choosing the right daily foods, and possibly supplementing, there is not yet conclusive evidence showing that vegan mothers are at risk, although it is likely that they are. One of the learnings that has come out of studies on omega-3 DHA is than vegan mothers may convert more vegan omega-3 ALA into DHA as an evolutionary imperative – not that a top up with supplementation isn’t still the recommendation. Could it be that vegan mothers make more choline if needed since it is so important for brain development? There are very few studies of vegans to know the answer to this question.

One recent study looked at choline levels in breast-milk of vegans, versus vegetarians and non-vegetarians. There was no significant difference with the author of the study concluding “This suggests that maternal plant-based diet by itself is not a risk factor for low breast-milk choline.” 

The vegan community is certainly divided on this issue. Of course, the safe or cautious position, while the science unravels, is to supplement choline during pregnancy.

What intake of choline can you achieve from a vegan diet alone? Here’s a list of the best plant-based food for choline, compared to egg and fish as a yardstick, listed in order of how much you could get in a reasonable serving*:

FOOD CHOLINE PER SERVING PER 100g

An egg (all in the yolk) 50g 113mg  226mg

Fish eg salmon (100g/3oz) 90mg 90mg

Soya milk (cup – 250g) 57mg 23mg

Shiitake mushrooms (1 cup/145g) 54mg 37mg

Soya flour 12.5g (a cake slice) 24mg 192mg

Peas (1 cup -160g) 47mg 30mg

Quinoa, raw (1/3 cup 60g) 42mg 70mg 

Beans, raw (1/3 cup – 60g) 40mg 67mg

black, white, pinto, kidney

Broccoli, cauliflower 

or sprouts (1 cup/91g) 36mg 40mg  

Tofu (half a cup-125g) 35mg  28mg

Hummus (1/2 cup) 34mg 28mg

Chickpeas (1/4 can) 33mg 33mg

Baked beans (1/4 can) 31mg 31mg

Flaxseeds (small handful) 22mg 78mg

Pistachio (small handful) 20mg 71mg

Pine nuts (small handful) 18mg 65mg

Cashews (small handful) 17mg 61mg

Wholegrain bread (2 slices – 50g) 17mg 34mg

Avocado (1/2) 14mg 28mg

Almonds 50g (small handful) 12mg 42mg

Peanuts (small handful) 12mg 42mg

Wheatgerm (tablespoon 7g) 12mg 178mg

Almonds or peanut butter (tbsp) 10mg 61mg

Source: USDA choline content database and https://nutritiondata.self.com

*Many foods have not been analysed for choline, and measurements do vary, so this is a guide rather than a definitive list.

What does this mean for your daily diet? Here’s a typical vegan daily menu aimed to maximise choline intake and how much it would give you (I’m not including all foods and recipes, just those ingredient that deliver significant amount of choline):

BREAKFAST

A cup of soya milk 57mg

Small handful of nuts or seeds 20mg

(Flax, chia, almonds etc)

LUNCH

A cup of cooked quinoa (1/3 cup raw) 43mg

A serving (100g) of either broccoli, 36mg

cauliflower or Brussels sprouts

Avocado (1/2) 14mg

SNACKS

A tablespoon of almond or peanut butter 10mg

Hummus (1/2 cup) 34mg

Two slices of wholegrain bread 17mg

DINNER

A serving of tofu (125g) or beans 35-40mg

Half a cup of shiitake mushrooms 27mg

A serving (100g) of either broccoli, 36mg

cauliflower or Brussels sprouts

TOTAL 332mg

In reality you are unlikely to achieve this every day, and it would be quite limiting on your food choices, so a realistic target would be to achieve 300mg of choline from food. If you are aiming to achieve 500mg, which is the low end of optimal – more than this may be optimal in pregnancy – that leaves a shortfall of around 200mg of choline, suggesting the need for supplementation.

The most direct source of choline is from soya-derived lecithin granules and capsules. A flat tablespoon of lecithin granules (7.5g), which has a neutral and pleasant taste and can be sprinkled on cereals, in shakes and soups or eaten as is, provides 1,500 mg of phosphatidylcholine and around 200mg (13 per cent) of choline. Some ‘high phosphatidyl choline’ lecithin, sometimes called ‘high PC lecithin’ is 18 per cent choline, thus you need less – approximately a flat dessertspoon.

One tablespoon of lecithin granules equals three 1,200mg lecithin capsules (if ‘high PC’ two capsules would suffice). We suggest that this is a sensible addition to a completely vegan diet. (If you aspire to be plant-based most, but not all of the time the addition of two eggs, or an egg and a fish serving, would achieve 500mg a day of choline.)

You can also find ‘brain food’ supplements providing a combination of different kinds of phospholipids, not just choline, but its hard to get enough choline from these if your only other food sources are plant-based foods. 

In summary, we need both omega-6 and omega-3 fats, as well as phospholipids.

Have one or two servings a day of dark green, leafy veg – especially those that grow in colder climates such a kale, broccoli, brussels sprouts, or a serving of seaweed as sources of both choline and omega-3.
Have a serving of quinoa, beans or tofu every day, if not two, for choline.
Have a dessertspoon of high PC lecithin, or two capsules of high PC lecithin granules every day. These guidelines are especially important if you are planning a pregnancy, pregnant or breast-feeding.

If you are not completely vegan the best food source for phospholipids and choline are eggs. Eat six eggs a week. The choline is in the yolk. The advice regarding omega-3 – eat three servings of fish a week, is good for choline too but it is present in all fish, not just oily fish high in omega-3 fats.

Have you taken the Cognitive Function Test to find out your Dementia Risk Index score? It’s completely FREE and you can choose to pay for the COGNITION programme afterwards if you need personalised recommendations to help you put diet and lifestyle tips into action.

The BBC’s recent story headed ‘Dementia: Brain check-up tool aims to cut risk at any age’ is a step in the right direction since early prevention is the key to reducing risk. However, the online brain health check, hosted by the Alzheimer’s Research Trust, is very basic, with only a dozen questions, and ignores the key evidence-based and common nutritional risk factors for Alzheimer’s disease. It covers ‘stay sharp’ which is about mental stimulation, ‘stay connected’ which is about social interaction and ‘love your heart’. 

What the test ignores

It ignores the two strongest nutritional risk factors, namely homocysteine lowering B vitamins and omega-3 intake from seafood. The US National Institute for Health’s research [1] attributes 22% of Alzheimer’s risk to each of these. 

‘Love your heart’ gives advice to keep your cholesterol and blood pressure in check and manage diabetes. This refers an individual to their GP who is likely to prescribe statins to lower cholesterol and hypertensive drugs to lower blood pressure. Neither reduce Alzheimer’s risk. A recent major review [2] of the evidence concludes ‘prospective, randomized, placebo‐controlled clinical trials that have failed to provide evidence for the benefit of statin therapy’ and there is ‘insufficient [evidence] to tell us whether reducing BP for dementia risk reduction is effective.’

The same review recommends omega-3 supplementation is start early and maintained and B vitamin supplementation to lower homocysteine, which is cited as the most evidence-based prevention approach considered. This report says “In view of the high population attributable risk, it is important that raised homocysteine can readily be lowered by the oral administration of three B vitamins (folate, B6, and B12). The doses of these vitamins that are required to lower homocysteine are considerably larger than can readily be obtained from the diet.” This is based on evidence of the VITACOG trial [3] which was part funded by the Alzheimer’s Research Trust.

A GP could lower a person’s risk much more effectively by measuring homocysteine in the blood and recommending B vitamin supplements, as well as upping omega-3 intake by eating fish and/or supplementing. This combination has reduced the rate of brain shrinkage by up to 73% in those with pre-dementia [4] but only few GPs do.

The Think Brain Health check does not assess diet, or make specific recommendations, and there’s no mention of protective  supplements, but refers people to the NHS’s ‘eight tips for healthy eating’. These recommend ensuring starchy carbohydrates make up over a third of what you eat, reducing saturated fat and salt. There is no evidence that these reduce risk for Alzheimer’s. Too many carbs may actually be a promoter of cognitive decline. They also recommend eating less sugar, lots of fruit and veg and having at least 2 portions of fish a week, including at least 1 portion of oily fish. There is evidence that these recommendations may reduce dementia risk.

Food For the Brain’s Cognitive Function Test

In sharp contrast foodforthebrain.org’s validated Cognitive Function Test and Dementia Risk Index questionnaire (139 questions) both objectively measure a person’s cognitive function and calculates their risk, then gives specific and actionable instructions as to how a person can reduce their risk, inviting them back every six months to track their progress.

The Cognitive Function Test is free and for those who wish to improve, we have launched COGNITION, a new way to Upgrade your Brain at a low cost of just £5 per month. You can access both tests once logged into your account.

References

1. Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.

2. Peters R, Breitner J, James S, Jicha GA, Meyer PF, Richards M, Smith AD, Yassine HN, Abner E, Hainsworth AH, Kehoe PG, Beckett N, Weber C, Anderson C, Anstey KJ, Dodge HH. Dementia risk reduction: why haven’t the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. Alzheimers Dement (N Y). 2021 Dec 8;7(1):e12202. doi: 10.1002/trc2.12202. PMID: 34934803; PMCID: PMC8655351.

3. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010 Sep 8;5(9):e12244. doi: 10.1371/journal.pone.0012244. PMID: 20838622; PMCID: PMC2935890.

4. Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(2):547-57. doi: 10.3233/JAD-150777. PMID: 26757190; PMCID: PMC4927899.

A recent study of 1,178 women found that those carrying the APOE4 gene taking Hormone Replacement Therapy (HRT) had a better delayed memory score compared to APOE4 carriers that were not taking HRT, and to non-APOE4 carriers.[1] They also had slightly larger brain volumes in certain areas. This study suggested that HRT may help to prevent Dementia. This study was an observational trial, not a clinical trial, meaning the statement remains a hypotheses and requires further randomised controlled trials to investigate further. We analysed the paper and provided our comments below.

Clinical Trials on HRT

Clinical trials to date have not shown benefit of HRT with improving cognitive function. A systematic review of the clinical trial evidence for the effect of HRT on cognitive outcomes did not find benefit.[2] The Women’s Health Initiative Memory Study (WHIMS) conducted a double-blind, placebo-controlled clinical trial examining 8300 women 65 years of age or older over a 2- year period to observe the effects of HRTs and dementia progression. The trial failed to find a beneficial effect for HRT in reducing dementia risk, instead finding an increase in all types of dementia.[3]

The ApoE4 Gene

Roughly 1 in 5 people carry the ApoE4 gene, which accounts for 4 to 6% of risk for dementia and can be modified, downregulating the gene, with positive diet, nutritional supplement and lifestyle changes.[1]

Find out your risk for Dementia

In our Dementia Risk Index, as part of the Cognitive Function test, and COGNITION programme to reduce dementia, we excluded HRT because the evidence was not conclusive or consistent.

Have you tried our free Cognitive Function Test yet? Find out your Alzheimer’s disease risk using our evidence backed Dementia Risk Index. If your risk is high, our clever new programme COGNITION can help you make the right nutrition and lifestyle changes to help improve your score.

References

[1] Saleh RNM, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther. 2023 Jan 9;15(1):10. doi: 10.1186/s13195-022-01121-5. PMID: 36624497; PMCID: PMC9830747.

[2] Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1(1):CD004143.

[3] Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in post- menopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651-2662.