If you’ve heard of Leqembi and Kisunla – the game-changing dementia drugs – you might have scratched your head when recent headlines claimed their effect on dementia was ‘trivial’. I examine the review that made the headlines and find unexpectedly good news for boomers like us.
Main Points
- A recent review analysed 17 clinical trials of anti-amyloid drugs;
- It sought to answer two questions: 1. Do they work? 2. Do they harm?
- The study results were clear and correlated with earlier, independent studies;
- What they point to are safer, more effective ways to protect our brains.
Those ‘Trivial’ Headlines
Here are some of the headlines that appeared around the world in April 2026:
‘Effect of anti-amyloid Alzheimer’s drugs “absent or trivial”,’ Cochrane review finds’ – Scientific American.
‘Effect of “gamechanger” Alzheimer’s drugs “trivial” ‘ – The Guardian
‘Alzheimer’s drugs targeting amyloid do not produce clinically meaningful effects, concludes Cochrane review.’ – British Medical Journal
‘Cochrane finds Alzheimer’s drugs ineffective, as experts slam the review.’ – Healthed
These drugs were hailed by proponents as breakthroughs in the fight to treat Alzheimer’s disease, but a new independent review finds they make “no meaningful difference“.
If you’re wondering, Cochrane isn’t a person but an independent review organisation. More below.
So Who Cares?
Anyone concerned about dementia might care, because this review questioned the basis for the last 20 years of dementia research – including the two game-changers.
You see, back in 1992, the ‘Amyloid Cascade Hypothesis’ proposed that plaques of amyloid in people’s brains caused dementia and, since then, hundreds of drug candidates have been focused on wiping them out. (Read more here.)
This new review looked at a range of amyloid-reducing drugs and asked two simple questions:
- Does reducing amyloid clinically impact dementia?
- Does reducing amyloid do any harm?
How Was The Review Done?
To answer these two questions, the authors systematically reviewed the clinical trials of amyloid-reducing drugs: 17 trials of 15 drugs. Of the 15, 12 drugs hadn’t gained FDA approval, three had, and two of them are still on the market: the two game-changers, Leqembi (lecanemab) and Kisunla (donanemab). I’ll use their generic names (the ones in brackets) from now on, to be consistent with our sources.
To be included in the new review:
- The trials had to be of the highest standard (Randomised Controlled Trials or RCTs) and conducted over at least 18 months (results were compared at the 18-month point);
- The drugs had to be monoclonal antibodies (the ‘mab’ part of the drug name) that focused on reducing beta-amyloid;
- The mode of action (how they reduced amyloid) didn’t have to be the same.
In other words, the authors wanted to know if reducing amyloid mattered, regardless of how it was done or whether the drugs had been approved or not.
Also, to be clear, this was a systematic review – a study of studies – not a new clinical trial.
Who Conducted The Review?
Cochrane is short for The Cochrane Collaboration, a global, independent, non-profit network of health researchers and professionals whose main concern is verifying results of clinical trials. Unlike some collaborations which are partly funded by the companies whose trials they review, Cochrane is not.
Scientific American describes its work as ‘gold-standard, independent analysis of the evidence for and against specific health interventions or treatments’. In other words, Cochrane’s reviews are generally well accepted.
What Did The Review Say?
Cochrane’s conclusions were blunt:
‘Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease.’
In other words, reducing amyloid didn’t seem to have much effect on dementia.
The authors were also concerned about harm:
‘Amyloid‐beta‐targeting monoclonal antibodies increase the risk of amyloid‐related imaging abnormalities.’
These ‘abnormalities’ aren’t unexplained errors in imaging, they’re actual changes in patients’ brains detected by MRI scans. They’re common in people taking these two drugs and can be serious, like brain swelling and brain bleeding.
Further, the authors said: ‘Future research on disease‐modifying treatments for Alzheimer’s disease should focus on other mechanisms of action.’
So, What Does It Mean?
In plain language, continuing to reduce amyloid, regardless of what mechanism is used, probably won’t make any more impact on dementia; maybe it’s time to look elsewhere.
This brings to my mind the definition of insanity: doing the same thing time and time again, hoping for a different outcome. It won’t happen and you might go nuts in the process.
In summary, the review concluded that reducing amyloid may not meaningfully affect dementia but may cause harm, and future studies shouldn’t continue to pursue this direction.
This isn’t the first time amyloid as a dementia drug target has been questioned (the landmark experiment that proved it has been under a cloud since 2022). Cochrane is important because it’s the first time clinical trial data of 15 amyloid-reducing drugs have been analysed side by side, by an independent body. (More amyloid and dementia here.)
Future research on disease‐modifying treatments for Alzheimer’s disease should focus on other mechanisms of action.’
Did Others Agree?
As you can see from the media quotes at the top, not all experts agreed with Cochrane.
They varied on theme, summarised by the quote below from Bart De Strooper, group leader at the UK Dementia Research Institute at University College London (UCL), which was cited in Applied Clinical Trials. (There are many more at the UK Dementia Research Institute website.)
“By mixing failed drugs with the only antibodies that have actually changed clinical practice, it turns therapeutic progress into statistical noise.”
In other words, the failed drugs unfairly weighted the results of those which succeeded.
This would be a fair point if the successful drugs had shown spectacular clinical results. They didn’t.
A detailed analysis of lecanemab and donanemab’s clinical trials – long before the Cochrane review – showed that these drugs slowed the absolute rate of cognitive decline over 18 months by 3% – at best. That is, thinking and memory in patients who took the drugs declined 3% more slowly than those who didn’t.
I guess you can see why the terms ‘trivial’ and ‘no meaningful difference’ were used by Cochrane: patients and their loved ones probably wouldn’t notice a change this small.
By mixing failed drugs with the only antibodies that have actually changed clinical practice, it turns therapeutic progress into statistical noise…
Bart De Strooper, group leader at the UK Dementia Research Institute at University College London
Put Into Perspective
Even so, you can also see why the experts who disagree with Cochrane would continue to support the amyloid drugs: at least these drugs are doing something for dementia, even if it’s not much.
That said, there are drugs that make more impact than the amyloid-reducing game-changers and they’re a fraction of the cost.
These are drugs that modify symptoms – like memory loss, confusion and agitation – and include names like donepezil, rivastigmine and galantamine. The snag is, they don’t arrest progress of dementia – they just modify symptoms short term – so the disease get worse. These drugs also have adverse effects, but less serious ones.
So the symptom modifiers offer a bit of peace of mind, but only for a short time.
That’s why modifying the disease – not just easing symptoms short term – has been the focus of drug development for two decades. The reality is that amyloid-reducing drugs do modify the disease but by so little, few will notice.
(See the pie graph above for the split between these two types of dementia drugs.)
Alzheimer Disease: Are the Treatments Worse Than the Illness?
What’s The Good News?
So, whichever way you look at it – the individual trials of lecanemab and donanemab or the Cochrane review including them – the amyloid-reducing drugs probably won’t make much impact on dementia.
The good news is, this bad news is now out in the open.
As a result, anyone concerned about dementia probably doesn’t have to fret about the huge cost of the game-changing drugs or how long before governments subsidise them, or worry about the cost of ongoing brain scans or the brain swelling or bleeding they may find.
Perhaps boomers could choose not to worry about dementia drugs at all.
Instead, they could channel their energies into safe, effective ways to strengthen their brains – either before or after a dementia diagnosis – knowing that there is a wealth of independent evidence to support them.
How Exactly?
Let’s compare those same two game-changing dementia drugs with non-drug approaches, rather than comparing with other anti-amyloid drugs (as Cochrane did).
Below is a summary, where triallists were all elderly people with or without Mild Cognitive Impairment (MCI or early stage dementia) at the start of each study. As we saw above, RCT is short for Randomised Controlled Trial.
Comparison of Approved Anti-Amyloid Drugs With Non-drug Interventions
1. Lecanemab and Donanemab as Therapies for Alzheimer’s Disease: An Illustrated Perspective on the Data
2. “MIND Diet” Foods May Prevent Alzheimer’s & Age-Related Cognitive Decline
3. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease
4. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial
From this, it seems that non-drug interventions could improve cognitive function (delay or reverse decline), whereas anti-amyloid drugs could just slow the rate of decline. (I provide more examples with links below. The ones cited in the table above allowed the most direct comparison with the two drugs.)
By the way, a recent Randomised Controlled Trial of non-drug interventions (reference 8 below) showed that Mild Cognitive Decline could be reversed, making an impact that was 7.5-times that of the same two drugs. (I didn’t include it above because its data tables were too complex, but it’s definitely worth a read. The results graphs for cognitive score, complex memory, executive function, processing speed and more are very clear.)
What’s The Bottom Line?
As you’ll see if you read the references, the researchers who believe that dementia is modifiable without drugs mostly agree on these premises:
- Dementia is a metabolic disease (genes affect only 10% of cases);
- It’s caused by many factors, not accumulation of one protein in the brain;
- It develops over years, but improvements can be measured within months;
- Most of the causative factors are under our own control;
- In most cases, dementia can be prevented or delayed;
- If found early enough, dementia can be reversed.
This is the sort of good news that should be emblazoned across very newspaper around the world but, apart from us boomers – the ones most affected by dementia – the media and others seem singularly disinterested.
They seem far keener to grab our attention with stories of war, politics or miracle drugs than give us the science of DIY dementia prevention. So be it.
Two Recurring Themes
Checking the table above and the non-drug dementia studies, you may notice two recurring themes:
- The impact of diet (the fuel for that vital metabolism of the brain);
- The effect of exercise (on the rate of oxygen available to the brain).
(Other factors play roles, too, like stress, toxins, certain prescription drugs and poor sleep.)
It’s extraordinary how two such simple factors can have such critical impacts on our most precious assets – our brains – and it’s wonderful news.
Of course, it not just a matter of that vague ‘eat a healthy diet and get enough exercise’ suggestion from our doctors. The benefits are in the detail: the specific types of foods that benefit the brain (and those that harm it) and the specific types of exercise that directly benefit the brain.
Getting The Specifics
If you’ve read my first eBook, Dementia: Keep Your Marbles, you’ll know the high-level science behind how diet and exercise help to protect our brains.
You’ll also know that I love food and won’t diet for any reason, even protecting my brain. That’s why I wrote a companion eBook about eating to protect the brain, without going hungry or giving up the good life.
I felt that that most boomers would be like me: I love my food too much to diet but I do want a strong, resilient brain. If this sounds like you, you may like to see what’s inside Anti-Dementia Food. It’s a no-diet, no-nonsense guide to cooking brain superfoods into delicious meals you’ll never get tired of.
I’m also just finishing the second companion eBook called Anti-Dementia Moves.
It’s about how little you need of specific movements (with no need for equipment, sweat or gym membership) that make a big impact on your brain, your mobility and your independence. It’s been a joyous journey of discovery and I can hardly wait to share it with you.
Regardless of whether you read further or not, please be assured that, these days, most independent dementia researchers agree on one thing – and it’s the best news of all: ‘dementia is not a normal part of ageing and you don’t have to get it’.
ANTI-DEMENTIA FOOD
How you can feed your brain with real food
Those Other Studies
Other successful studies of non-drug interventions for early-stage dementia:
5. Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project
6. Preventing Alzheimer’s: Our Most Urgent Health Care Priority
7. Findings of a Pilot Study Investigating the Effects of Mediterranean Diet and Aerobic Exercise on Cognition in Cognitively Healthy Older People Living Independently within Aged-Care Facilities: The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study
8. Precision Medicine Treatment of Alzheimer’s Disease: Successful Randomized Controlled Trial
9. Signs of Alzheimer’s were everywhere. Then his brain improved
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