Patrick Holford

New Drug for Alzheimer’s Disease May Slow Cognitive Decline

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Patrick Holford, (2022, September 30). New Drug for Alzheimer’s Disease May Slow Cognitive Decline. Psychreg on Psychiatry & Neuroscience. https://www.psychreg.org/new-drug-alzheimers-disease-slow-cognitive-decline/
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After 40 failed trials for drugs injecting anti-amyloid antibodies (AAAs) one, Lecanemab, has finally shown a modest benefit on cognitive function in those with early-stage Alzheimer’s. But they come with a terrible cost: adverse effects that include brain swelling and haemorrhage which occurred in one in five trial participants.

When a similar drug, Aducanumab, was conditionally approved by the US FDA last year, despite 9 out of 10 of their experts voting against it, many resigned in protest. Yet the pressure on pharma to get an amyloid drug to market, having spent over $42 billion, is immense.

Let’s consider the alternative: prevention with simple, doable changes to diet, lifestyle and supplementation with B vitamins and omega-3 fish oils.

The two most relevant measures of success of any treatment are a reduction in the rate of brain shrinkage and a reduction in clinical dementia symptoms which lead to a diagnosis.

In relation to brain shrinkage, the best AAAs have achieved is 2% less brain shrinkage. In a landmark trial by Professor David Smith and colleagues at the University of Oxford, B vitamin supplements, given to those with pre-dementia (mild cognitive impairment) have achieved a reduction in the rate of brain shrinkage of 52%, up to 73% in those with sufficient omega-3. This effect was shown in those with raised blood levels of homocysteine, a marker for B vitamin status that is raised in approximately half of the pre-dementia patients and many more with Alzheimer’s. We now know that B vitamins need omega-3 to make the biggest difference, and vice versa.

What about actual clinical improvement, called Clinical Dementia Rating (CDR), which is what counts for the person concerned? A CDR score of zero means no clinically significant cognitive impairment. In the Oxford trial on B vitamins, 65% of participants on B vitamins with higher omega-DHA status ended the two-year trial with a clinical dementia rating of zero compared with 25% receiving a placebo.

In a Swedish omega-3 trial those with sufficient B vitamin status also had a marked reduction in clinical dementia rating, measured by the CDR sum of boxes (CDR-SB), which was reduced by 1.5 points compared with placebo after 6 month’s treatment with omega-3.

The improvement in clinical dementia rating reported for Lecanemab, which was a modest absolute difference in the score, out of 18, of 0.45 as measured by CDR-SB. This was marginally better than a 0.39 difference for Aducanumab, compared to placebo. In other words, no AAA drug has even reduced CDR-SB score by 1 point.

A trial in Holland, called B-proof, which had shown no significant effects overall in those supplementing B vitamins, recently reported that those with higher Omega-3 levels had a significant improvement in cognitive function. A French and Chinese study reported a similar finding – the combination of B vitamins and omega-3 shows clear improvements in cognitive function – better than achieved by AAA drugs, without adverse effects.

So, on all three counts – brain shrinkage, cognitive function and clinical dementia rating – B vitamins plus omega-3 – wins out at a fraction of the cost since nutrients cannot be patented which is the requirement for the scale of profitability required by pharma.

But, there are two other points to make. Firstly, B vitamin and omega-3 status are but two of eight known actions that reduce risk or improve these critical criteria. Others are sugar, antioxidant-rich fruit and veg, vitamin D, exercise, cognitive stimulation, gut health, sleep and stress. Having a high blood sugar level from age 35 predicts Alzheimer’s risk. Being diabetic or having high insulin levels, which is a consequence of eating too much-refined sugar and carbs, doubles the risk. Having a high carb intake is associated with increasing amyloid plaques in the brain – so why not tackle the upstream cause? 

One study reported that those who ate the healthiest diet had an 88% decreased risk of developing dementia and a 92% decreased risk of developing Alzheimer’s disease.

Increasing lean muscle mass with resistance exercise is associated with better cognitive function and brain volume. The charity Food for the Brain has a free, validated online cognitive function test, followed by a Dementia Risk Index questionnaire, that not only measures your cognitive function but also shows you exactly what your risk is and how to reduce it by targeting your ‘weakest links’ in these eight known prevention steps.

Then, there’s the issue of side effects. For each of these prevention steps, there are none. Or rather, there are plenty – less risk for diabetes, heart disease, arthritis, premature ageing, better energy, sleep and weight control to name a few.

For AAA drugs, the side effects are potentially devasting. Since 1 in 5 can be expected to experience brain swelling and microbleeds, regular brain scans will be necessary to monitor for these frequent complications. Is it right to expose an older person with cognitive decline to this scale of risk and medical intervention for such a modest benefit? The annual cost of treatment is expected to be above $10,000 but that doesn’t include the cost of medical monitoring or the cost of treatment when things go wrong. The cost-benefit equation just doesn’t add up.

Writing in the Financial Times last year Professor Smith: ‘Your editorial is correct in saying “A resurrection of the amyloid approach must not divert resources and attention away from other ways to tackle dementia, which are in earlier stages of research and might give better results.” These alternative approaches include identifying and then treating modifiable risk factors for dementia, of which about a dozen are already known. These account for about half of the cases of Alzheimer’s disease.’

The high price proposed for the drug is disturbing, especially when a very much cheaper alternative treatment is available: high doses of B vitamins and omega-3 from seafood or supplements. He estimates that early intervention, targeting all the prevention steps recommended by Food for the Brain could cut a person’s risk by two-thirds.


Patrick Holford is a nutrition and mental health expert. He is the founder of the Institute for Optimum Nutrition Advice, VitaminC4Covid, and the charitable Food for the Brain Foundation, which studies how to prevent Alzheimer’s disease.


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