Recently, a clinical trial was released using a drug-free ‘precision medicine’ approach to treating dementia. The results published were impressive – 4-7 times the impact of the two currently-approved drugs, the authors said – but can we believe them? I look beyond for proof beyond this trial.
Main Points
- The drugs compared are Lecanemab (from Eisai-Biogen) and Donanemab (from Eli Lilly);
- Both drugs target amyloid plaque in the brains of those with Alzheimer’s Disease;
- The clinical trial claimed improvements 4-7-fold higher than for these drugs;
- External evidence suggests that this claim is not over-stated.
For starters, here’s a link to the trial report: Precision Medicine Treatment of Alzheimer’s Disease: Successful Randomized Controlled Trial. For brevity here, I’ll refer to it as the Bredesen 2025 RCT as Dr Dale Bredesen was the driving force behind it and is possibly the most recognised of the authors.
(If you’re curious how all this fits into the bigger picture of dementia risk and prevention, you may care to peak inside my everyday-English summary of the latest research, my eBook, Dementia: Keep Your Marbles.)
The Trial Results
For context, the trial compared precision medicine to the current ‘standard care’ for dementia: training and stimulation but no intake of drugs to modify symptoms or the disease. That is, there was no placebo (no treatment at all) because it would have been unethical to withhold standard care from patients suffering from the disease.
Compared to standard of care, the precision medicine group showed improvements in:
- Neurocognitive functioning, composite memory, executive function, processing speed, cognitive symptom severity, and Alzheimer’s disease symptoms;
- Blood pressure (heart risk), body mass index (overweight risk), glycemic index (diabetes risk), lipid profiles (cholesterol), and methylation status (inflammation).
In other words, patients showed improvements in brain function (as measured) and in disease symptoms (as observed) as well as in health overall: their brains improved and so did their health. You can read the full analysis here, complete with graphs from the report.
The Two Drugs
Of over 400 candidates, only four drugs that ‘modify’ dementia have been approved, as distinct from drugs that just ease dementia symptoms. Two drugs were withdrawn (Tacrine and Aducanemab) due to lack of effect, serious side effects or both. Two remain on the market:
- Lecanemab (Leqembi from Eisai-Biogen) approved by the FDA in 2023; and
- Donanemab (Kisunla from Eli Lilly) approved in 2024.
1. Performance
Both of these drugs target amyloid plaque (or amyloid-beta) in the brains of dementia sufferers – said to be the cause of dementia. Both drugs reduce amyloid and so, it is believed, slow the rate of cognitive decline – the rate at which memory and thinking fade. The headline figures for drug performance in the trials were impressive:
- Lecanemab slowed cognitive decline by 27% over 18 months; and
- Donanemab slowed it by 35% over 18 months.
To be clear, both drugs slowed the rate of memory and thinking loss, not the loss itself. That is, patients didn’t experience roughly one third lower loss; they experienced loss slowed by one third.
The problem is, even these figures are statistical sleights of hand: they compared the drug and placebo to each other (relative reduction), not comparing both of them over 100 trialists (absolute reduction).
The absolute slowing of cognitive decline was less impressive – 2.5% for Lecanemab and 2.3% for Donenemab – independent analyses confirmed. That is, the rate of loss of memory and thinking was slowed by less than 3% (not ~30%) over 18 months, a difference ‘below the individual threshold of perception for most patients’.
This is a very deceptive figure...(the change) is so small that most patients probably would not be aware of the difference in their trajectory.
No wonder Harvard Medical School said ‘It (lecanemab) will just make Grandma forget a tiny bit less’ and the The Lancet’s editorial said: ‘many patients will ‘wrongly expect the medication (lecanemab) to improve their memory and thinking skills’.
2. Side Effects
The modest performance of these drugs isn’t the only issue.
Adverse side effects are common. In their respective clinical trials, 45% of patients suffered side effects with lecanemab, 89% for donanemab. In other words, half the patients or more suffered side effects like brain swelling and brain bleeding. The side effect numbers gained far less attention than the headline figures; the latter still quoted as proof that these drugs work.
3. Price
Another issue is price.
Because of the frequency of side effects, all patients taking these drugs must have regular monitoring for brain damage. By the time the costs of genetic tests, frequent brain scans (MRI, CT, ultrasound), safety monitoring and other care are added to the drug costs (roughly USD25,000 each), the total per person in the USA can be up to USD100,000 per year. The Bredesen Protocol of Precision Medicine, called ReCODE (Reversing Cognitive Decline), costs less than USD2,000 a year.
In concluding his analysis of the two drugs, Professor Alberto Espay from Cincinnati Uni, was blunt. These are his words in quote highlighted below:
The small and uncertain benefits, the worrisome and poorly understood risks, and the very high costs of treatment suggest that these drugs are promoted largely out of theoretical rather than practical benefits. For patients and society—both of whom bear the costs of this treatment—caveat emptor.
Prof. Alberto Espay University of Cincinnati, USA
Perhaps you can see why governments in the UK, Canada, NZ and Australia are reluctant to pay for these drugs. Even in the USA, coverage by government and private insurance is limited. In the other countries, these drugs are approved but there is no government subsidy. That is, if patients want to use them, they pay the full price.
Maybe, it’s a case of too little bang for too many bucks, with too much collateral damage?
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(If you haven’t read it yet – and want to know what researchers say about the causes of dementia and how to prevent, delay or reverse it – including Bredesen’s ReCODE – you may like to explore what’s inside Dementia: Keep Your Marbles.)
DEMENTIA:
KEEP YOUR MARBLES
How you can prevent, delay, even reverse Alzheimer’s Disease
