Home Mental Health & Well-Being New Drug for Alzheimer’s Accelerates Rate of Brain Shrinkage by 20%

New Drug for Alzheimer’s Accelerates Rate of Brain Shrinkage by 20%

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Don’t be fooled by the rhetoric promoting the new Alzheimer’s anti-amyloid drug. The results – increased brain shrinkage, a third getting brain bleeding or swelling and no clinically meaningful benefit – are not good.

However, reading this week’s headlines claiming a “turning point” in the fight against Alzheimer’s, you’d be mistaken in thinking something new has occurred since Eli Lilly’s press release regarding their new drug, “donanemab”, a month ago.

This week’s front pages stimulated the publication of the actual study in the Journal of the American Medical Association, giving more details of the results. This was reported positively in every major newspaper.

Yet not one reported that the drug treatment accelerated the rate of brain shrinkage by over 20% compared to placebo. The paper states, “At 76 weeks, MRI [scans] showed a greater decrease in whole brain volume”.

This is consistent with a meta-analysis of all anti-amyloid treatments, including “donanemab”, in the journal Neurology earlier this year, which concluded that: “Mild cognitively impaired participants treated with anti-amyloid drugs were projected to have a material regression toward brain volumes typical of Alzheimer’s dementia approximately eight months earlier than if they were untreated.”

In contrast, in treatment with homocysteine-lowering B vitamins, given to those with sufficient omega-3, “the rate of atrophy was significantly slowed by circa 70%”. B vitamins and omega-3 are only two of eight established prevention steps you can take yourself.

Alzheimer’s is characterised by brain shrinkage, particularly in the “hippocampus”, part of the medial temporal lobe at the brain’s centre. The new drug treatment was not associated with accelerated hippocampus shrinkage, just the whole brain. 

There was a very small reduction, of about 1%, in the shrinkage rate in this area of the brain compared to the placebo. The B vitamin study showed an 80% reduction in shrinkage in the medial temporal lobe.

While it is theoretically possible that, having selected people with lots of plaques, then targetting them with an aggressive drug, the brain may have shrunk as part of the process of amyloid destruction, this is not yet known, and therefore, this increased brain shrinkage is worrying.

The other main measure of Alzheimer’s and dementia, made by a health professional, is the Clinical Dementia Rating (CDR). This includes interviewing the patient’s carer or partner and thus is potentially subject to “hopeful” bias.

The new drug treatment results show a statistically significant improvement, showing just over half a point (0.67) less worsening, compared to placebo, on the 18-point CDR scale. But is this small change meaningful? A study in the Lancet suggests that minimum changes of 0.98 in mild cognitive impairment and 1.63 in mild Alzheimer’s disease are meaningful. This study was on those with early Alzheimer’s.

In contrast, a trial giving omega-3 fish oils to those with adequate B vitamin status showed more than double this beneficial clinical effect. In another, giving homocysteine-lowering B vitamins to those with adequate omega-3, almost two-thirds of the trial participants ended the trial with an overall Clinical Dementia Rating of zero.

This means they were no longer diagnostically labelled as having cognitive impairment. In other words, not less bad, but better.

Serious adverse effects, including deaths

More details in the recent “donanemab” paper were given on the adverse effects and trial deaths. “Treatment-emergent adverse events’ were reported by 759 of 853 participants (89%) receiving “donanemab” and “Either amyloid-related imaging abnormalities of oedema/effusion [swelling] or micro haemorrhages [bleeding] occurred in 314 participants (37%) receiving “donanemab”.

Also, in the “donanemab” group, three participants with serious amyloid-related imaging abnormalities subsequently died. Over a third had brain bleeding or swelling, and one in 287 died.

This compares to no adverse events in the B vitamin and omega-3 trials or other prevention approaches. If any nutritional supplement had anything like these adverse effects, it would be banned, not licenced.

According to the Financial Times, this new treatment will cost $26,000 a year (in addition to medical costs, including numerous scans). In the UK, this would be paid by the taxpayer. In contrast, taking homocysteine-lowering B vitamins, eating fish and/or having fish oil supplements would cost 20p or cents a day – less than £100 a year.

So, the question is, would you rather take a treatment that markedly slows both whole brain and medial temporal lobe shrinkage than a treatment associated with a greater loss of brain volume, a high risk of adverse effects and high costs?

The big push is to get approval from the UK’s NICE (National Institute for Health & Care Excellence) and the drug licensed in Europe. NICE has previously refused to consider the evidence for homocysteine-lowering B vitamins and omega-3, which is now overwhelmingly positive when both these nutrients are combined.

That is why we at Food for the Brain aim to make sure as many people as possible know that the real turning point for Alzheimer’s is prevention through diet, nutrition and lifestyle improvements, not expensive drugs with dangerous side effects.

You can take the free Cognitive Function Test yourself, and we encourage everyone to do so and take control of their brain health for the future.


Patrick Holford is a nutrition and mental health expert and founder of the Institute for Optimum Nutrition, VitaminC4Covid, and the charitable Food for the Brain Foundation

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