{The pharmaceutical company Eisai claims that, unlike drugs that are already approved for treatment of Alzheimer’s, this one is able to slow the progression of the process rather than decrease the symptoms. This is a good thing, but, is only the first step towards finding an effective treatment for Alzheimer’s. As experts in neuroscience, specializing in Alzheimer’s research, we are following the search for treatment options for this condition extremely closely. We offer the knowledge of academics to the public. Promising but modest findings Lecanemab is an antigen that is able to attach to beta-amyloid protein accumulated in the brain and allows the immune system to get rid of the proteins. In Alzheimer’s this protein is formed into aggregates and is thought to be a factor in the beginning of the progress in the course of disease. Eisai so chose patients with the greatest chance of benefitting from the treatment: those who are in the initial phases of disease, or those suffering from mild cognitive impairments that have a large amount of beta-amyloid. That’s the situation with about seven-in-eight people with a diagnosis of Alzheimer’s, and for about the majority of people with slight cognitive impairment. After 18 months of treatment, one-third of those treated had normal levels of beta-amyloid. A treatment of 18 months with lecanemab slows functional and cognitive loss by 27 per cent in patients with mild Alzheimer’s disease or Alzheimer’s-related cognitive impairment. (Shutterstock) This isn’t the first time a product has gotten rid of beta-amyloid, but this is the first time that a treatment has led to statistically clear cognitive and functional benefits. The effect, however, is small: on the 18-point scale for rating clinical dementia the patients who were treated lost one-half of a point. The effect on the life of a person who is treated is therefore minimal. Because Alzheimer’s disease is slow in the early stages of the disease, it is vital to establish if the effects persist for more than 18 months. Unsettled side effects does not come with all positive news. It caused a 25 per cent faster reduction in the size of brain. Researchers have linked these atrophy results to removal of beta-amyloid. However, this is not an accepted notion in all circles, since the brain levels of beta-amyloid are not sufficient to account for this shrinkage. The implications of shrinkage are not known. One-sixth of those treated developed cerebral edema — the accumulation of water which indicates inflammation. The treatment also led to more cerebral hemorrhages — approximately one in six — compared to those who received the placebo. But, just one out of 30 people actually experienced symptoms related to these two conditions. Although minor microhemorrhages are common in the elderly they can affect the brain’s capacity to adapt. This may increase the brain’s vulnerability to Alzheimer’s disease. Fortunately, certain subgroups of patients might benefit more from this therapy. Men and people who are 75 or older were able to enjoy a 40% reduction in cognitive decline. People without an e4 version in the APOE gene, the principal risk factor for Alzheimer’s had fewer adverse negative effects, but experienced a more slower progression of the disease. Conversely, people carrying two copies of APOE the e4 variant — which comes from both parents — are six times as likely to develop symptoms from cerebral hemorrhage, or even edema. In addition, these people did not generally experience any positive effects from lecanemab. Having a single copy of APOE e4 seems to allow patients to benefit from the treatment but also increase the chance of experiencing side effects. These data offer hope that healthcare experts will be able to identify patients who are the most likely to benefit from the treatment. A treatment that is resource intensive All indications are that lecanemab will be resource intensive. Before we can give lecanemab to patients we must ensure that the brain of the patient has significant concentrations of beta-amyloid. This requires expensive imaging equipment, as well as a team of well-trained professionals. The antibody will also need to be administered every two weeks, requiring greater involvement from patients as well as their family members and health experts. To reduce the chance of adverse side effects, regular imaging will also be essential. In addition, there is the cost of the medication itself that hasn’t yet been revealed. According to experts it could cost close to $20,000 annually. In short, the health-care system as well as scientists will need invest significant funds in order to provide this new treatment to the most equitable number of people. More medical and neuropsychological follow-ups will be required, and new brain imaging facilities will have to be built and specialized personnel will have to be trained. We should be hopeful that this new approach is worth the effort. Let’s also hope that future clinical trials will show higher efficacy for women as well as in people with APOE e4. After all, lecanemab is just the beginning, and more is required to completely cure Alzheimer’s disease.
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