Analysis: Drugs, limited benefits in Alzheimer's disease

Drugs developed to slow the progression of Alzheimer's disease may have a much smaller impact than initially hoped, according to a recent analysis carried out under the auspices of Cochrane. Researchers claim that the effects of these treatments are "insignificant" from a clinical point of view, despite some apparently promising statistical results. The analysis included 17 clinical trials, carried out on a total of more than 20,000 patients with mild cognitive impairment or dementia. Among the drugs evaluated were: lecanemab, donanemab, aducanumab,

bapineuzumab, crenezumab and solanezumab (withdrawn after failures in the studies). The main conclusion: after about 18 months of treatment, cognitive improvements were "either non-existent or too small to be noticed by patients and caregivers". Neurologist Edo Richard stressed that the differences identified are "well below the minimum threshold necessary to matter in real life."

• Potential risks: edema and cerebral hemorrhage

In addition to limited effectiveness, researchers draw attention to important adverse effects: cerebral edema (swelling of brain tissue), cerebral hemorrhages detected by imaging. Although in many cases these effects did not produce immediate symptoms, their long-term impact remains uncertain. Not all experts agree with the conclusions of the analysis. Representatives of organizations in the field, such as the Alzheimer's Society, argue that the results are presented too pessimistically. The main criticism: the study combines older drugs, which have failed, with newer therapies, considered partially effective. Thus, the positive effect of recent treatments would be "diluted" in the overall analysis. In fact, regulatory authorities have assessed that some drugs, such as lecanemab and donanemab, still offer a modest benefit, especially in the early stages of the disease.

• The difference between "statistically significant” and "clinically significant”

A key point highlighted by the researchers is the difference between: statistical significance - measurable differences in studies, clinical relevance - real, perceptible benefits for the patient. As neurologist Francesco Nonino explains, many studies can show "positive” results on paper, without these translating into a concrete improvement in the lives of patients. The duration of most studies - around 18 months - is considered relatively short for a slowly evolving disease like Alzheimer's. It is possible that the real effects of treatments become more evident in the longer term, but this remains to be demonstrated. In parallel, institutions such as the National Institute for Health and Care Excellence are re-analyzing the data on these drugs, including the impact on quality of life and the costs to health systems.

• Caution and hope

The message from doctors remains a balanced one: it is essential that patients and their families receive realistic information, without creating unrealistic expectations. At the same time, for many families affected by dementia, even a few months' delay in cognitive decline can mean precious time, an argument that maintains interest in continuing research. Although anti-amyloid treatments do not represent, for now, a revolutionary solution, they remain an important piece in a much more complex puzzle of the fight against Alzheimer's disease.