A recent review concludes that drugs designed to slow Alzheimer’s disease progression deliver no meaningful benefits to patients and increase the risk of brain swelling and bleeding. Researchers found the effects on early-stage Alzheimer’s and dementia patients to be either absent or consistently small.
Review Highlights Limited Impact
The Cochrane review analyzed 17 studies with 20,342 participants, mostly aged 70 to 74, who had mild cognitive impairment, dementia, or both. It included trials for lecanemab, donanemab, and discontinued drugs like aducanumab, bapineuzumab, crenezumab, and solanezumab.
After 18 months, the drugs showed trivial effects on cognitive function and dementia severity. Edo Richard, professor of neurology at Radboud University Medical Centre in the Netherlands, noted that trial results over two decades remain inconsistent. He emphasized that the differences fall far below the minimal noticeable effect for patients and caregivers.
Experts Weigh In on Efficacy
Francesco Nonino, neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna in Italy, stated: “Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients. There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect.”
Nonino highlighted that while early trials showed statistical significance, these do not always translate to clinical relevance. He also pointed out the 18-month study duration as relatively short for a slowly progressive condition like Alzheimer’s, noting potential longer-term use in practice.
Richard, who operates a dementia clinic, informs patients candidly about the small effects, burdensome requirements like frequent IV infusions, scans, and tests, and side effect risks. He shared: “I think you will probably not benefit from these drugs, and they’re burdensome for you and your family. It’s extremely important that we’re honest to our patients about what they can expect.”
Brain Swelling and Bleeding Concerns
The review identified heightened risks of brain swelling and bleeding, detectable on scans but often asymptomatic. Long-term consequences remain unclear.
Charities Challenge the Conclusions
Dr. Richard Oakley, associate director of research and innovation at the Alzheimer’s Society, argued that combining failed and successful trials paints an overly bleak picture. He noted that UK regulators approved lecanemab and donanemab for modest but meaningful benefits in early-stage Alzheimer’s, urging nuanced interpretation.
Jonathan Schott, professor of neurology and group leader at the UK Dementia Research Institute at UCL, explained that grouping varied drugs, many ineffective against beta-amyloid and failed in trials, inevitably leads to findings of overall clinical ineffectiveness.
Dr. Susan Kohlhaas, executive director of research at Alzheimer’s Research UK, stressed that even months-long delays in decline offer valuable time for families. She cautioned against broadly dismissing anti-amyloid treatments, as they differ in action, and research targets broader mechanisms.
NHS Re-evaluation Underway
Lecanemab and donanemab await NHS approval after NICE deemed benefits too small for costs. NICE now re-examines evidence following appeals by manufacturers Eli Lilly and Eisai, focusing on caregiver quality of life and NHS infusion costs.
