Positive Health Online

You may have heard of a search for new tests to find those most likely to get Alzheimer’s disease. But is this misdirected?

Perhaps so, according to the Alzheimer’s Prevention Expert Group (APEG) –  a collaboration of top UK, American and Chinese academics who consider this to be “..a misguided waste of money”.  Controversially, their stance challenges the major thrust of charities such as Alzheimer’s Research (ARUK), which strongly supports the search for a reliable test for the disease. APEG explains that there is already a widely used way to spot failing memory and thinking skills - hallmarks of dementia and Alzheimer’s. These include a neuropsychological test battery (NTB) and a Cognitive Function Test (CFT).

Both are routinely used in memory clinics to diagnose mild cognitive impairment and support the diagnosis of dementia. Over the last decade, the charity foodforthebrain.org  has used the CFT to find people at risk and advise them on how to reduce their risk with simple dietary and lifestyle changes. They have already tested nearly half a million people to date.

Cognitive function declines steadily from the age of 18. This means that it is possible to spot individuals whose cognitive function is dropping off faster than the average, giving time to encourage preventative actions with personalised advice on their diet and lifestyle changes.

Mainstream Testing

Alzheimer’s, which makes up two-thirds of dementia cases, involves the shrinking of certain areas of the brain as neurons die off. It can be detected with a specialised brain scan several years before a diagnosis. These ‘PET’ scans can be used to diagnose Alzheimer’s and/or vascular dementia.  The trouble is that such scans are expensive and not likely performed early enough to discover those ‘at risk’. 

As well as shrinkage, another marker for Alzheimer’s is a toxic protein called p-tau. This creates clumps of tangled nerves in the brain. These can be found in the fluid that bathes the brain, but again there is a problem. Detecting it can be done with a lumbar puncture, but this is a risky and expensive process and certainly not suitable for testing tens of thousands of people. 

At first sight, if a blood test could identify those heading towards Alzheimer’s earlier this could be a cheaper and less invasive alternative to such scans. However, the search is likely driven by a quite different ulterior motive – to create and sell drugs – much like cholesterol and statins. What’s more its unlikely to be an improvement!

A recent New York Times article pointed out that, such a test would result in people being diagnosed with ‘pre’ Alzheimer’s, even if they have no obvious symptoms. That’s because having the marker would be considered enough to justify a diagnosis of the disease or, at least, the prescription of a drug.

This is what happens with amyloid protein. Amyloid forms plaque in the brains of those with Alzheimer’s. The latest drugs, such as lecanemab and aducanumab, remove this. But not all those with Alzheimer’s have plaque, and people can develop dementia without plaque. What’s more none of these drugs have a clinically significant effect, and they come with the risk of severe adverse effects, including death from brain bleeding and swelling, especially in those with a history of stroke.

Perhaps the most convincing reason why the new blood marker hunt is ‘misguided’ is that there is something very cheap and very safe that can prevent the accumulation of p-tau tangles in the brain – B vitamins.

Cognitive Function and Nutrient Tests

If you are not taking in enough B6, folate or B12, which becomes harder to absorb as you get older, blood levels of a toxic amino acid called homocysteine rise. This increases the level of p-tau and inhibits the brain from clearing it. According to pharmacology professor David Smith, a member of APEG (foodforthebrain.org/apeg): “Homocysteine is not a diagnostic marker for dementia, but it is a modifiable risk factor. Raised levels of homocysteine account for some 20% of dementia cases and homocysteine testing is relatively inexpensive and available.”

Smith, who was second in charge at Oxford University’s School of Medical Sciences, ran the VITACOG trial which found that high doses of B vitamins given to people with Mild Cognitive Impairment (MCI) and high homocysteine, not only slowed the rate of brain cell death by up to 73% but also arrested cognitive decline. He, and his APEG colleagues, favour using a Cognitive Function Test, which is free, to identify those at risk then testing risk factors and biomarkers such as homocysteine to be included in the research funds being made available for testing blood biomarkers because this is one thing you can actually do something about.

Other useful tests for risk factors include omega-3 and vitamin D levels, since low levels of these nutrients also increase risk; and HbA1c, the standard measure used to diagnose diabetes, since lower levels help protect the brain and high levels indicate those who need to reduce their intake of sugar and processed foods.

These tests are corroborative rather than diagnostic but importantly they identify prevention actions that people can take. This two-step paradigm of testing cognitive function early then having further blood tests, such as homocysteine, omega-3, vitamin D and HBA1c for glucose control, help guide diet and lifestyle prevention.

The Glutathione Index Test

More recently, a simple home pin-prick blood test, The Glutathione Index test, has become available, which can predict your dementia risk. Your brain consumes more energy than any other organ. This combustion creates exhaust – oxidants – that age your brain. These oxidants also make skin wrinkly, and joints stiff and literally create inflexibility in the brain that leads to cognitive decline.

Those with diets high in antioxidant foods literally halve their risk for dementia compared to those with low intakes, according to a recent study of 2,716 people aged over 60.[1]

Also, critical antioxidants such as vitamin C and vitamin E, if supplemented together, reduced the risk of developing Alzheimer’s by as much as two-thirds.  Taking either cut risk by a quarter in a study of 4,740 elderly residents of Cache County, Utah.[2]

A study of all studies to date demonstrated that ‘either a high vitamin E or high vitamin C intake showed a trend of attenuating [dementia] risk by about 26 per cent’ according to China’s leading Alzheimer’s prevention expert Professor Jin Tai Yu of Fudan University in Shanghai. This study shows that these nutrients are ‘grade 1’ top level dementia prevention factors.[3]

Vitamin C, which is water based and protects you against smoke and pollution, and vitamin E, which is fat based, and protects you from burnt and fried fats are both in the bloodstream outside of cells. Once the Vitamin C has been used by the body it is ‘spent’ or ‘oxidized’. This oxidised vitamin C is reloaded, in other words, returned to its useful, active antioxidant state, by glutathione. Spent (oxidised) vitamin E is reloaded by Co-enzyme Q10, which is why these nutrients are often included together in antioxidant supplements.

https://foodforthebrain.org/are-blood-tests-for-alzheimers-a-misguided-waste-of-money/

Outside Your Cells

Inside cells, especially brain cells, is the most potent antioxidant of all; glutathione. It is the master antioxidant. Your glutathione status is the best measure of your anti-ageing potential, keeping brain and body actively rejuvenated. The charity foodforthebrain.org has developed a simple home pin-prick test, called the Glutathione Index, to help you know if your brain is ageing too fast.  

Every second there are hundreds of thousands of metabolic ‘fires’ going on inside the energy factories in our brain cells. Think of Glutathione as the water in the fire engine. It gets rapidly used up keeping your brain protected. The ‘spent’ or oxidised glutathione, much like steam, then has to be cooled to reload the fire engine. This is done by vitamin C and an enzyme called Glutathione Reductase, returning Glutathione back to its fully loaded active antioxidant form. How Glutathione and vitamin C recycle each other is one of the hottest discoveries in brain anti-ageing.

https://foodforthebrain.org/are-blood-tests-for-alzheimers-a-misguided-waste-of-money/

Inside Your Cells

Brain scientists have discovered that the ratio between the fully loaded Glutathione and the spent Glutathione, called the Glutathione Index, identifies risk for dementia. This is what the charity is measuring and researching, along with the free Cognitive Function Test, which anyone can take.

The worse the ratio, the worse a person’s cognitive function is. It’s a bit like having a direct measure of how fast your brain is ageing “Patients with dementia have a reduction in glutathione and its ability to be recycled. [4] This ratio, the Glutathione Index, is a biomarker for many diseases, including both type 1 and 2 diabetes, liver cirrhosis, multiple sclerosis and Alzheimer’s disease.” says Dr Konrad Kowalski, the analytic chemist in the brain team which has developed the Glutathione Index test at Food for the Brain’s lab.

“It’s too early to know the perfect number but it is looking like a Glutathione Index of 500 means your brain can roll with the punches, while below 200 a person definitely needs to be both changing their diet and supplementing antioxidants. Having a way to measure brain ageing with a home test kit from a pin prick of blood, means we can realistically see what the impact of specific diet changes and antioxidant supplements might be.”

Further Information

Foodforthebrain.org is looking for volunteers to both take the blood test (which costs £69) and complete a Cognitive Function Test and a diet and lifestyle questionnaire now, then in three months, and again six months later. The volunteers will also follow, as best as possible, personalised advice on how to increase their antioxidant potential to anti-age their brain.

Patrick Holford is founder of foodforthebrain.org, a not-for-profit independent registered charity, and Chair of the Alzheimer’s Expert Group.  https://foodforthebrain.org and https://foodforthebrain.org/apeg

Evidence

The VITACOG trials, evidence for homocysteine as causal and lowering it with B vitamins as disease modifying and a consensus statement regarding this evidence, in the Journal of Alzheimer’s Disease, is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836397/

The validation of foodforthebrain.org’s Cognitive Function Test in the International Journal of Geriatric Psychiatry is here: https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.3993

The evidence in relation to p-tau and homocysteine is here: https://foodforthebrain.org/the-p-tau-delusion/

References

1. Peng, M., et al. Dietary Total Antioxidant Capacity and Cognitive Function in Older Adults. J Nutr Health Aging (2023).
2. Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124. doi: 10.1177/1060028016673072. Epub 2016 Oct 5. PMID: 27708183.
3. Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020;91(11):1201-9. Epub 2020/07/22. doi: 10.1136/jnnp-2019-321913. PubMed PMID: 32690803; PMCID: PMC7569385.
4. Martínez de Toda I, Miguélez L, Vida C, Carro E, De la Fuente M. Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer's Disease. J Alzheimers Dis. 2019;71(1):153-163. doi: 10.3233/JAD-190198. PMID: 31356205.; see also Park SA, Byeon G, Jhoo JH, Kim HC, Lim MN, Jang JW, Bae JB, Han JW, Kim TH, Kwak KP, Kim BJ, Kim SG, Kim JL, Moon SW, Park JH, Ryu SH, Youn JC, Lee DW, Lee SB, Lee JJ, Lee DY, Kim KW. A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase. Clin Psychopharmacol Neurosci. 2023 Nov 30;21(4):758-768. doi: 10.9758/cpn.23.1053. Epub 2023 Jul 14. PMID: 37859449; PMCID: PMC10591176; see also Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009 Feb-Apr;30(1-2):1-12. doi: 10.1016/j.mam.2008.08.006. Epub 2008 Aug 30. PMID: 18796312; PMCID: PMC2696075.