Experts challenge the Cochrane findings, arguing newer Alzheimer’s therapies deliver modest but meaningful benefits, despite the review’s negative conclusions.
Leading Australian dementia researchers have pushed back against a newly released Cochrane review questioning the effectiveness of anti-amyloid therapies for patients with Alzheimer’s.
They warn the review’s conclusions could misrepresent the clinical value of a new generation of treatments already reshaping Alzheimer’s disease care.
As reported in The Medical Republic last week, the researchers said their review showed that anti-amyloid medications had no clinical benefit for people with early Alzheimer’s disease.
The Australian Dementia Network (ADNeT) said it was concerned the review’s conclusions were based on a pooled analysis that included early-stage drugs and subtherapeutic dosing regimens long known to be ineffective and abandoned during development.
The Cochrane review, published in the Cochrane Database of Systematic Reviews, analysed 17 randomised controlled trials involving more than 20,000 participants and found that while anti-amyloid monoclonal antibodies reduced amyloid plaque burden on imaging, this did not translate into meaningful improvements in cognition, function or independence over 18 months.
It also identified increased rates of amyloid-related imaging abnormalities, including brain swelling and microbleeds.
“[The review] is the best independent test of whether a dramatic effect on amyloid PET scans translates into a meaningful benefit for patients,” Professor Vissel from the School of Clinical Medicine at UNSW told media last week.
“Its answer is sobering. Even when plaques are successfully cleared, the hoped-for improvements in memory, thinking, daily function and independence do not meaningfully follow. In plain English, these drugs clear plaques far more convincingly than they preserve memory, thinking and independence.”
But ADNeT director Professor Chris Rowe said combining unsuccessful early compounds with newer, optimised therapies distorted the findings and failed to reflect how modern anti-amyloid drugs were developed and used.
“The inclusion of earlier failed drugs shown not to work is illogical and distorts the results of the final review,” he said.
“These early-stage drugs were from trials where the drug was shown not to work as they did not reduce the amyloid on PET scans and so were abandoned as treatments.
“Learning from these earlier failed drugs led to the successful development of newer drugs at the right dose, proven to remove amyloid plaques and slowing of decline in memory and thinking.
“This is the standard trial and error approach for research to develop new therapies for any disease or health condition.”
The dispute comes as Australia enters a pivotal phase in Alzheimer’s treatment following approval by the Therapeutic Goods Administration of two anti-amyloid therapies, lecanemab and donanemab, over the past year.
Both agents have demonstrated modest slowing of disease progression in phase III trials, although neither is currently listed on the Pharmaceutical Benefits Scheme, limiting access.
Professor Rowe characterised the therapies as an incremental but significant advance, comparing their emergence to early chemotherapy and antiretroviral treatments.
“We are at the beginning of a revolution in innovative ways to treat, diagnose and prevent dementia. These new anti-amyloid therapies are the most significant breakthrough in decades for the treatment of Alzheimer’s,” he said.
“The benefit is modest as they buy time but do not cure the disease. This is like the first treatments that emerged with chemotherapy for cancer or anti-HIV drugs for AIDS. Over time new drugs were added, resulting in much greater long-term benefits.
“This is where the treatment of AD now sits. Current research and trials will develop drugs that add to the benefit from anti-amyloid treatments. Treatment of a disease is more effective when given early.”
Professor Rowe said ADNeT was trialling new blood tests for AD for widespread use to “make earlier diagnosis and therefore better treatment outcomes a reality”.
“Bringing these innovations to the Australian community in a timely and equitable way will improve outcomes for patients and their families and reduce long term costs to our health and aged care systems,” he said.
“Negative stories from this distorted review cannot be allowed to detract from the momentum and progress in Alzheimer’s early diagnosis and treatment over the past 24 months.”
Critics of the amyloid hypothesis, including Professor Vissel, argued the Cochrane analysis represented the most rigorous independent assessment to date and raised fundamental questions about whether plaque reduction should remain the central therapeutic target.
Despite measurable reductions in amyloid on PET imaging, the review found effect sizes on cognitive and functional outcomes were small and below thresholds typically considered clinically meaningful.
The review also reinforced safety considerations, with higher rates of amyloid-related imaging abnormalities observed in treated patients, although serious adverse events and mortality were not significantly increased.
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For clinicians, the divergence highlights an increasingly nuanced therapeutic landscape, where modest efficacy signals must be weighed against risks, cost and patient expectations, particularly in early-stage disease where treatment appears most effective.
ADNeT has called for sustained national investment aligned with the federal government’s National Dementia Action Plan to ensure timely and equitable access to emerging treatments.
With dementia now the leading cause of death in Australia and cases projected to more than double by 2065, the stakes remain high.
For health professionals, the debate underscores a central tension in contemporary Alzheimer’s care – whether incremental slowing of decline constitutes meaningful benefit and how best to translate evolving evidence into practice.
