The Food and Drug Administration’s (FDA) approval of lecanemab in 2023 marked a significant milestone in the treatment of Alzheimer’s disease. This novel therapy has been shown to modestly slow disease progression in clinical trials. However, concerns about side effects, such as brain swelling and bleeding, have led some patients and physicians to hesitate about using the medication.

Researchers at Washington University School of Medicine in St. Louis conducted a retrospective study to investigate the adverse events associated with lecanemab treatment in their clinic patients. The study, published in JAMA Neurology on May 12, focused on 234 patients with very mild or mild Alzheimer’s disease who received lecanemab infusions at the Memory Diagnostic Center.

The results of the study are reassuring. Only 1% of patients experienced severe side effects that required hospitalization. Patients in the earliest stage of Alzheimer’s, with very mild symptoms, had the lowest risk of complications. This information can help inform patients and clinicians as they discuss the treatment’s risks.

“This new class of medications for early symptomatic Alzheimer’s is the only approved treatment that influences disease progression,” said Barbara Joy Snider, MD, PhD, a professor of neurology and co-senior author on the study. “But fear surrounding the drug’s potential side effects can lead to treatment delays. Our study shows that WashU Medicine’s outpatient clinic has the infrastructure and expertise to safely administer and care for patients on lecanemab, including the few who may experience severe side effects, leading the way for more clinics to safely administer the drug to patients.”

Lecanemab is an antibody therapy that clears amyloid plaque proteins, extending independent living by 10 months, according to a recent study led by WashU Medicine researchers. The medication is recommended for people in the early stage of Alzheimer’s, with very mild or mild symptoms. In this study, only 1.8% of patients with very mild Alzheimer’s symptoms developed any adverse symptoms from treatment compared with 27% of patients with mild Alzheimer’s.

“Patients with the very mildest symptoms of Alzheimer’s will likely have the greatest benefit and the least risk of adverse events from treatment,” said Snider. “Hesitation and avoidance can lead patients to delay treatment, which in turn increases the risk of side effects. We hope the results help reframe the conversations between physicians and patients about the medication’s risks.”

The study found that most cases of amyloid-related imaging abnormalities (ARIA), a side effect associated with lecanemab, were asymptomatic and only discovered on sensitive brain scans used to monitor brain changes. Of the 11 patients who experienced symptoms from ARIA, the effects largely resolved within a few months, and no patients died.

“Most patients on lecanemab tolerate the drug well,” said Suzanne Schindler, MD, PhD, an associate professor of neurology and a co-senior author of the study. “This report may help patients and providers better understand the risks of treatment, which are lower in patients with very mild symptoms of Alzheimer’s.”

Overall, the study demonstrates that lecanemab can be safely administered and tolerated by most patients in a real-world setting, especially those with very mild symptoms of Alzheimer’s disease. This information can help alleviate concerns about side effects and encourage more patients to consider treatment with this novel therapy.

The intricate dance of protein quality control within cells has been revealed by researchers led by biochemist Alexander Buchberger at Julius-Maximilians-Universität Würzburg (JMU). A recent study published in Nature Communications sheds light on the crucial role played by the ubiquitin-selective unfoldase p97/VCP enzyme in eliminating malformed proteins and aggresomes.

In cells, proteins are constantly being produced, assembled, transported, and broken down. This delicate balance is vital to prevent serious illnesses, as even small changes can have devastating consequences. To maintain this balance, cells have developed complex systems to control protein quality. One such system involves the formation of aggresomes – a type of cage that collects and isolates proteins prone to clumping.

While the formation of aggresomes has been extensively studied, their protein content and degradation pathways remained poorly characterized. The recent study changes this by revealing that the breakdown of aggresomes requires multiple players, with p97/VCP enzyme emerging as the most critical.

The researchers conducted experiments blocking p97/VCP enzyme and observed that aggresomes no longer disintegrated and were destroyed. This indicates that p97/VCP plays a pivotal role in breaking down aggresomes into smaller components. The findings have significant biomedical implications, particularly for understanding neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

Mutations in the p97/VCP enzyme cause neuro-muscular degenerative diseases, including certain forms of dementia and ALS – amyotrophic lateral sclerosis. Moreover, disrupted degradation processes within cells could also contribute to Parkinson’s disease, which is characterized by Lewy bodies – roundish inclusions containing harmful protein deposits that disrupt nerve cell metabolism.

The research team concludes that their findings suggest mutations in the p97/VCP enzyme disrupt aggresome degradation, potentially contributing to Lewy body formation and neuro-muscular degenerative diseases. This study highlights the importance of understanding protein quality control mechanisms within cells and how disruptions in these processes can lead to devastating diseases.

The secret to aging successfully may not be what you think. Instead of focusing on physical exercise or mental stimulation alone, research suggests that cultivating curiosity can play a significant role in maintaining cognitive health and even preventing Alzheimer’s disease. An international team of psychologists has found that older adults who maintain a curious mindset and seek out new knowledge relevant to their interests may be able to offset or prevent dementia.

This finding challenges prior research that suggested curiosity decreases with age. The study, published in the journal PLOS One, was led by UCLA psychologist Alan Castel and involved a large sample of participants between the ages of 20 and 84. The researchers aimed to tease apart two types of curiosity: trait curiosity (a general level of inquisitiveness) and state curiosity (a momentary feeling of curiosity experienced when engaging with specific topics).

To assess these forms of curiosity, the researchers asked participants to complete an online questionnaire and guess answers to hard trivia questions. Analysis showed that while trait curiosity did decline across the adult lifespan, state curiosity increased sharply after middle age and continued upward well into old age.

The study’s lead author, Mary Whatley, notes that this finding may be related to selectivity theory, which suggests that as people get older, they become more selective about what they want to learn. This aligns with research on lifelong learning, where many older adults engage in activities like taking classes or picking up hobbies.

Castel’s own work on memory has shown that people tend to quickly forget information that doesn’t engage their curiosity. Anecdotally, many older adults report that staying curious is crucial for maintaining cognitive health and preventing dementia.

This study was supported by the National Institutes of Health’s National Institute on Aging, the Leverhulme Trust, and the Alexander von Humboldt Foundation. The findings suggest that cultivating curiosity can be a key factor in healthy aging and may even help prevent or offset Alzheimer’s disease.