‘Leqembi’ for Alzheimer’s: Defence or Dead End?

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Last year, Leqembi made headlines by becoming the first drug to gain full FDA *approval to treat Alzheimer’s Disease. Two others are in the pipeline, but how big a deal are these drugs? Are they the best defence for our precious boomer marbles? Just a month after approval, many were already saying no.

Main Points

  • Leqembi has been approved to treat Alzheimer’s in the USA but not in Australia yet;
  • Suitable patients must be in early stage Alzheimer’s & have ‘amyloid plaque’ in their brains;
  • To check this, a PET scan is needed beforehand, then ongoing to monitor changes in the brain;
  • Brain swelling, bleeding & shrinkage were side effects for some Leqembi trialists;
  • Experts say that Leqembi slows the rate of cognitive decline by so little, it may not be noticeable;
  • There are more direct, safer ways to combat Alzheimer’s Disease.

(If you’d like to go straight to direct ways to avoid, prevent or even reverse Alzheimer’s – especially for boomers – check out our short eBook Dementia: Keep Your Marbles.)

A Big Deal, Really?

On one level, Leqembi (generic name lecanemab) is a big deal. After 25 years and billions of dollars spent on Alzheimer’s Diseases (AD), it’s the first to gain full approval.

The Alzheimers Association said at the time, Leqembi ‘changes the course of the disease in a meaningful way‘ but, as we’ll see, the changes in patients are not only not meaningful, they’re mostly not detectable.

Perhaps groups like this were excited because major breakthroughs for AD have been few, and those few haven’t been star performers. In short, there hasn’t been a lot of good news for those worried about AD. By the way, it’s no secret that the Alzheimer’s Association also partly funded the development of Leqembi and its forerunner, Aduhelm.

Two Out Of Three Is BAD

It’s been 100 years since Alzheimer’s Disease was discovered and only three drugs have been approved to treat it.

All three emerged in the last 20 years. Two were withdrawn due to side effects (Tacrine and Aduhelm), which is why full approval wasn’t granted for them. Leqembi is the last candidate standing, so far. (Get the full history in our blog post).

Eli Lilly and Roche have drugs in Phase III clinical trials with results described as ‘promising’, but both are based on the same mode of action as Aduhelm and Leqembi, and all three of the new drugs have the same side effects as Aduhlem – brain swelling and bleeding – but at lower levels.

Another side effect of Leqembi is brain shrinkage, which is usually a measure of the progress of AD; that is, as the disease progresses, the brain usually shrinks.

As a Leqembi clinical trial side effect, brain shrinkage has been little reported. It fact, it’s been ignored, says Professor Scott Ayton, from the Howard Florey Institute of Neuroscience and Mental Health in Melbourne. We may hear more about this as more experts examine the trial data but, clearly, brain shrinkage is not a welcome effect from an AD treatment.

We’re talking about the possibility of brain damage (from a treatment)… I find it very peculiar that these data, which are very important, have been completely ignored by the field.

Scott Ayton, Neuroscientist, Howard Florey Institute of Neuroscience and Mental Health

On a Road to Nowhere

All up, there are two AD drugs withdrawn, one approved and two more in the pipeline.

Of these, four share the same mode of action – reducing a protein called ‘amyloid-beta’. This is a problem because this mode of action for treating Alzheimer’s has been questioned for decades.

Confused? Let me explain.

In drug development, it’s common to use a ‘biomarker’ or lab measurement to test if a drug works. It’s been the case since 1992 when the *FDA (the US Food & Drug Administration) introduced Accelerated Approval to speed up drug development for serious conditions with unmet need. It’s clear that Alzheimer’s Disease (AD) qualifies.

In AD research, the biomarker is ‘amyloid -beta’, a protein found in plaques in the brains of some AD sufferers. The trouble is, it’s also found in the brains of those without AD.

For 25 years, reducing this protein has been the yardstick for treating AD. That is, if amyloid-beta levels went down, the drug was a success. Yet, there were serious doubts about whether this ’cause and effect’ link existed, from as far back as the 1990s.

Ever since the 1990s, researchers and clinicians have been spending uncountable hours (and uncountable dollars) trying to turn the amyloid hypothesis into a treatment for Alzheimer’s’. Every single one of these interventions has failed in the clinic. Every last damn one.

Dr Eric Lowe, former AD researcher, in Science

More recently in 2022, Aduhelm was taken off the market in Europe because this link couldn’t be found. Others have said so for some time: Fierce Biotech editor Ben Adams says: ‘The amyloid theory just won’t die…the FDA has just resurrected it for a long and healthy future.’ Bloomberg agreed; ‘For Alzheimer’s patients, their families, researchers, and the pharmaceutical industry, the bigger question is whether drugs targeting amyloid have been a multi-billion dollar dead end.’

In other words, the longer the amyloid-beta hypothesis persists, the more drugs will be based on it, like the two in the pipeline from Eli Lilly and Roche.

How Effective Is Leqembi?

In the clinical trial that convinced the FDA to approve the drug, Leqembi slowed the rate of cognitive decline in early stage AD by 27% over 18 months; a benefit of 5.1 months. This does look like a big deal

But as Matthew Schrag, Assistant Professor of neurology at Vanderbilt School of Medicine, puts it, the 27% is a relative number, not an absolute one. He says: ‘this is a really deceptive number…the treatment really only improved patients’ condition by about 2.5% …most patients probably would not be aware of the difference.’ (Confused? See how being selective about numbers can skew results, in our blog post Risky Business: The 4 Medical Risk Numbers You Must Know.)

Schrag is not the only sceptic.

Other neurologists say: people on Leqembi just got worse slightly more slowly. Neuro-psychologist Karen Sullivan says much the same thing: ‘the real world impact of this may not be noticeable to families’. Jerry Avorn, professor of medicine at Harvard Medical School agrees: ‘It will just make Grandma forget a tiny bit less.’ In reality, she might start to forget a tiny bit less, slightly more slowly.

Meanwhile, many patients will ‘wrongly expect the medication to improve their memory and thinking skills’. That is, they’ll think that their symptoms will improve. They won’t; symptoms will just get worse slightly more slowly or the placebo effect may kick in and they’ll think their symptoms are improving.

You can understand why people may be optimistic, when patient advocate groups make pronouncements like: ‘The Alzheimer’s Association celebrates today’s U.S. Food and Drug Administration action to grant traditional (full) approval of Leqembi.’ Why, you might ask?

...this is a really deceptive number… the treatment really only improved patients’ condition by about 2.5%… most patients probably would not be aware of the difference.

Neurologist Matthew Schrag

You might expect groups like the Alzheimer’s Association to be independent advisories for people with Alzheimer’s yet, as we’ve seen, that’s not the case. They can be financially involved in developing drugs for the conditions on which they advise.

How Easy Is It To Get Leqembi?

This interview with Dr Bill Brooks answers this in detail.

In short, while Leqembi was approved in July 2023 in the USA, the TGA (Therapeutic Goods Administration) is still considering its approval in Australia. Currently, the only people with local access are patients on the Leqembi clinical trial.

If Leqembi does gain approval here, only patients with early stage Alzheimer’s (Mild Cognitive Impairment) and confirmed presence of amyloid plaque in their brains will be eligible. In other words, they must have amyloid plaque present before Leqembi can reduce it.

To confirm that will require a brain scan using PET (Positron Emission Tomography) which, according to Brooks, isn’t easy to get and is not covered by Medicare. Ongoing scans will also be required to monitor for brain swelling and bleeding.

In short, for now, Leqembi is not available Down Under.

How To Make a Real Impact on AD?

We’re told that Leqembi won’t improve patients’ memories or thinking skills, so why wait?

There are more direct ways to make a noticeable impact on these functions right now – but you probably won’t have heard about them. They’re based on independent trials in clinics around the world, but without industry funding, they haven’t made too many headlines.

As a snapshot, here is what a few of them have to say:

  • Dr Dean Sherzai: ‘….90% of us can avoid getting it, and for the 10% with strong genetic risk, the disease can be delayed by 10 to 15 years
  • Dr Dale Bredeson: ‘…our generation will be the last generation to fear Alzheimer’s Disease’.
  • Dr Timothy Smith: … whether you have a healthy, dementia-resistant brain is completely up to you
  • Dr Mark Hyman: ‘Dementia can be reversed if caught early enough, by attending to all the factors that affect brain function…’

‘….90% of us can avoid getting (dementia) and for the 10% with strong genetic risk, the disease can be delayed by 10 to 15 years

Dr Dean Sherzai, Consultant Neurologist, Loma Linda University, CA, USA

Below are just three ways to reduce your risk of dementia. There are many more (collected from around the world in our eBook Dementia: Keep Your Marbles). Some aren’t new and, the good news is, most are under your control.


Researchers from the Rush University Medical Centre in Chicago ran a couple of diet trials over 5 years, with almost 1,000 men and women aged 58 to 98. All were from retirement homes and none had dementia at the start of the trial.

They were put on the MIND diet, a combination of a Mediterranean Diet and the DASH diet (Dietary Approaches to Stop Hypertension). Their cognitive function was tested before, during and after the trial period, using 21 comprehensive measures.

At the end of the trials, the leaders concluded that ‘by eating the right foods, you could protect your brain from neuro-degeneration and slow age-related cognitive decline by up to 8 years’. That is eight years, not eight months.

(By the way, this was not a tiny trial. It’s was 60% of the size of the confirmatory trial (1800 people) for Leqembi that granted its final approval in July 2023.)

‘…by eating the right foods, you could protect your brain from neuro-degeneration and slow age-related cognitive decline by up to 8 years’.

MIND Diet Study reported in Mental Health Daily


In a smaller study over a much longer period, University of Gothenburg researchers tracked the fitness of 200 women from 1968 to 2012, to check the relationship between fitness and dementia.

Only 5% of the fittest women had developed dementia at the end of the 44-year study, compared with 32% of the women with a low fitness score. In the same study, researchers found that the onset of dementia in women with high fitness scores was 11 years later, compared to those with a medium fitness score. Sure, the trial was small, but the result was pretty clear.

Exercise reduces the risk of dementia in women ‘by almost 90 per cent.’

Title of the article reporting the Gothenburg study


As we saw, brain shrinkage is an indicator of the progress of AD and it’s measured directly in patients, not via biomarkers.

So, it was big deal in 2013, when Emeritus Professor David Smith and colleagues at Oxford University showed that giving vitamin B supplements to seniors with high homocysteine levels resulted in a 700% reduction in brain shrinkage. High levels of this amino acid are a known risk factor for Alzheimer’s disease and 40% of people over age 50 have them, so they’re very relevant to age and to AD.

As Malcolm Kendrick, doctor and author, put it: ‘Had any drug shown such a significant effect on brain shrinkage, I am 100% certain that the finding would have been shouted from the rooftops. We would be looking at a massive blockbuster. probably the biggest selling drug in the world – ever.’ 

Kendrick asks the obvious question: ‘Why, you might ask, is no-one doing anything about this?’ He gives the obvious answer, too: ‘..they (vitamins) cannot be patented; therefore any profit margin is far too puny to be of interest to them (drug companies).’ For that reason, it’s unlikely there will ever be drug industry funding into the efficacy of B vitamins or any other non-drug treatment, for Alzheimer’s.

That’s a pity because, if a tiny fraction of the drug research money were used for large-scale testing of non-drug-based dementia therapies, there would be mountains of data available for analysis by everyone. We’d all know once and for all, based on huge trials.

Had any drug shown such a significant effect on brain shrinkage, I am 100% certain that the finding would have been shouted from the rooftops. We would be looking at a massive blockbuster. probably the biggest selling drug in the world – ever.

Dr Malcolm Kendrick

AD Defence In Your Own Hands

In the meantime, there is a pile of research into the causes of AD and non-drug-based ways to prevent it, albeit a much smaller pile than for drug-based ways.

If you’d like a closer look, check out our eBook: Dementia: Keep Your Marbles.



Discover how Aussie boomers can delay or prevent Alzheimer’s Disease

Kim Brebach

Kim Brebach

Hi, I’m Kim Brebach, boomer, information researcher, technical writer and Joiner of Dots at M&M. In my spare time, I review wines and love to cook.

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