A UNIVERSITY OF Galway professor has said there is still “cautious optimism” around drugs that are said to slow the progression of Alzheimer’s disease despite researchers claiming they make “no meaningful difference”.

A new Cochrane review has examined data from 17 clinical trials with over 20,000 participants, all looking at the impact of anti-amyloid drugs on people with mild cognitive impairment or mild dementia due to Alzheimer’s disease.

Anti-amyloid medicines bind to the protein which builds up in the brains of people living with Alzheimer’s, clearing deposits and slowing down cognitive decline.

Edo Richard, professor of neurology at Radboud University Medical Centre in the Netherlands, said his team noticed that results from trials over the last two decades “are not consistent”.

The studies included trials on lecanemab and donanemab, as well as aducanumab, which has been discontinued by its manufacturer, in addition to bapineuzumab, crenezumab and solanezumab, which were discontinued after failed trials.

While lecanemab and donanemab are EU-approved, these therapies are not yet available through the HSE, though they are currently under review by the Health Products Regulatory Authority (HPRA).

The analysis found that the effects of these drugs on cognitive function and dementia severity after 18 months was “trivial”.

According to Richard, who runs a dementia clinic, the differences made by the treatments were “far below the minimal effect that’s needed to be noticeable at all for patients and caregivers”.

He added: “I just think it’s extremely important that we’re honest to our patients about what they can expect.

“There’s nothing more that I would like as a doctor to finally be able to prescribe them a drug that provides a bit more hope to the patients and their families, but I’m always wary to avoid giving people false hope.”

The drugs could also increase the risk of swelling and bleeding in the brain, according to the study.

These side effects were seen in brain scans and caused no symptoms for most patients, although the long-term impact was unclear.

‘More work needed’

Dr Andrea Kwakowsky, Associate Professor in Pharmacology and Therapeutics at the University of Galway, acknowledged that the review is “disappointing” but added that “more work is needed to fully understand the potential of these therapies”.

She noted that only lecanemab and donanemab have been approved and are currently marketed and said that they have shown “modest cognitive and functional improvements”.

However, Dr Kwakowsky also noted that a major review by Francesco Nonino, neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna, found these benefits fall short of what doctors consider clinically meaningful.

But Dr Kwakowsky said one of the most important things to note is that many of the drugs discussed in the Cochrane review were never approved.

She added that lecanemab and donanemab, which are approved, are “promising options still under active evaluation in ongoing trials to better understand their efficacy and safety”.

Dr Kwakowsky said this “distinction is crucial” and that the Cochrane researchers “make some very strong claims”.

“Despite the modest results to date, there is still cautious optimism that these therapies could be more effective in specific subgroups of patients,” said Dr Kwakowsky.

Meanwhile, she said that taking into account the APOE4 genotype “might be a game-changer”.

The APOE4 gene increases your risk of developing Alzheimer’s disease and is a major contributor to brain swelling and bleeding, which are the main risks of anti-amyloid therapies.

Dr Kwakowsky said the review authors considered a subgroup analysis arranged by APOE4 status but were unable to do so because testing for this gene is not part of usual clinical practice.

“By integrating genetic testing into trial design and treatment planning and adopting an early-disease-stage-specific individualised approach, a safer, more effective treatment may be achieved,” said Dr Kwakowsky.

She added that “several shifts are occurring in the field” and that the “key to success is a better understanding of the underlying biology of Alzheimer’s disease”.

Dr Kwakowsky said this could result in a more “systematic approach to the disease rather than focusing on the better-established targets such as amyloid”.

Meanwhile, Dr Kwakowsky remarked that the Irish health system will require a “major infrastructure upgrade and guidelines in place to allow people with Alzheimer’s disease to access these therapies.

She also called for clearer guidelines, earlier and more accurate diagnosis, and robust monitoring to ensure patient safety.

-With additional reporting from Press Association