For the First Time, We Can Slow Alzheimer's

The battle against Alzheimer’s disease has ushered in a transformative era. The introduction of new medications that modestly slow its progression, coupled with the identification of biomarkers that facilitate early detection, has reignited hope for addressing a condition that currently impacts 50 million individuals globally. After years of challenges and the inability to discover effective treatments for a form of dementia that undermines memory and personal autonomy, the scientific community is observing a promising diagnostic and pharmacological evolution. A panel of experts shared a series of articles in The Lancet on Monday, shedding light on these advancements and discussing the significant controversies surrounding the new treatments — the first to modify the disease's trajectory, yet criticized for their high costs, potential side effects, and limited efficacy.

Juan Fortea, the head of the Neurobiology of Dementia group at the Sant Pau Research Institute and co-author of one of the articles in The Lancet, asserts that Alzheimer’s research is experiencing a “paradigm shift.” He clarifies, “While we are not curing the disease, this marks the first time in human history that we have been able to decelerate the progression of Alzheimer’s.”

This pivotal scientific advancement is driven by a new class of drugs designed to eliminate beta-amyloid protein, which accumulates in affected brains and contributes to the disease's progression.

Albert Lleó, head of Neurology at Sant Pau in Barcelona, emphasizes that this represents merely “the beginning of the journey”: “There are an additional 138 drugs currently under investigation. These are just the first among many to emerge.”

Research is also delving into the potential of semaglutide, which has already transformed obesity treatment.

The drugs generating significant hope are lecanemab and donanemab. In clinical trials, lecanemab demonstrated a 27% reduction in disease progression, while donanemab showed a 35% reduction. Both medications have received approval in the United States and several other countries, although the European Medicines Agency (EMA) has taken a more cautious approach, initially delaying lecanemab's approval until a year ago and still evaluating donanemab.

Both treatments have sparked considerable debate, even within the scientific community. Concerns have been raised regarding potential side effects — for instance, lecanemab has been associated with cerebral hemorrhages and the deaths of two patients — as well as skepticism about the clinical benefits: what does a 27% reduction in disease progression truly mean for families in their daily lives? Additional worries include the estimated annual cost of around $25,000 per patient and the fact that these drugs are intended for a very specific subset of patients in the early stages of the disease.

In the Lancet series, the authors — some of whom have disclosed conflicts of interest due to affiliations with the pharmaceutical companies producing these drugs — explore the “range of reactions” and the “skepticism” these medications have incited within the scientific community, questioning whether a similar response would have occurred with treatments for other diseases.

They draw comparisons between the efficacy, cost, and impact of the new Alzheimer’s treatments and other biologic drugs used for various conditions. For example, while serious adverse effects occurred in 1 in 300 patients treated with lecanemab and 1 in 65 with donanemab, trials of pembrolizumab (an immunotherapy for lung cancer) reported side effects in 27% of cases. Furthermore, the reduction in disability observed with anti-amyloid drugs for Alzheimer’s is comparable to that seen in trials of biologic drugs for rheumatoid arthritis or multiple sclerosis.

Based on the historical context of other biologic treatments across different diseases, the authors contend that the magnitude of effect may be strikingly similar. They note that in past instances, prices were similarly high, and side effects were not absent. Regarding the limited access for a niche group of patients — with experts estimating that currently only 5% of Alzheimer’s sufferers will benefit — the authors point out that in multiple sclerosis, the use of innovative drugs was restricted to 36% of patients in 2017, but this figure rose to 74% by 2020.

“What these authors are proposing is not a direct comparison with other diseases, but a demonstration that other medical therapies have yielded comparable effects, yet Alzheimer’s is often viewed through a lens that undervalues these advancements,” explains David Pérez, head of Neurology at the 12 de Octubre Hospital in Madrid, who did not participate in this series. He identifies several factors, including scientific skepticism and societal prejudices, that have fostered an environment ripe for controversy.

Pérez observes that the history of drug development for Alzheimer’s has been “bumpy,” characterized by repeated failures that have sown distrust within the scientific community. The contentious approval of aducanumab, a drug that was sanctioned in the U.S. under questionable circumstances but ultimately failed commercially and was retracted by its manufacturer, has further exacerbated this mistrust. “It was approved in a convoluted manner, without clear benefits, which generated an atmosphere of skepticism,” Pérez elaborates.

Nihilism and ageism also play significant roles in the discourse surrounding this disease, according to Lleó: “Often, diagnoses are not made accurately, and in the absence of effective treatments, the public lacks the impetus to seek timely diagnoses, as seen with conditions like stroke or cancer. Symptoms are frequently dismissed as part of normal aging. This perception contributes to the notion of a disease with limited avenues for intervention.”

Pérez further notes that ageism is a critical factor influencing the debate: “This disease predominantly impacts older individuals, who often lack the means to advocate for themselves and demand action from society. These patients represent a vulnerable demographic.”