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Leqembi’s Effectiveness Hinges on Sex: A Re-Examination of Alzheimer’s Modifying Drug

A research team has found that lecanemab was probably less effective in females than males in its Phase 3 trial. However, there was insufficient evidence to say the drug was totally ineffective in females.

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The latest Alzheimer’s-modifying drug, Leqembi (lecanemab), has been making waves since its approval by the American Federal Drug Administration (FDA) in 2023. Sales of this groundbreaking medication have surged to $87 million USD in the last quarter of 2024. However, a closer look at the Phase 3 clinical trial data reveals an intriguing disparity: lecanemab appears to be less effective in females than males.

In its Phase 3 trial, lecanemab demonstrated a significant slowdown in cognitive decline, with a remarkable 27% reduction overall. However, a subset of data suggested little to no benefit for female participants. The cause of this difference remained unclear, leaving some researchers questioning the prescribing of Leqembi to females.

A recent study conducted by McGill PhD candidate Daniel Andrews and neuroscientist Prof. Louis Collins aimed to re-examine the Phase 3 trial data using simulated trials on openly available Alzheimer’s patient data. Their findings confirmed that lecanemab was indeed likely less effective in females than males. Nonetheless, there was not enough evidence to conclude that the drug is entirely ineffective in females.

It’s essential for clinicians to be aware of this disparity when considering Leqembi as a treatment option for female patients. The potential benefits of the medication must be weighed against its possible side effects. These findings also highlight the importance of future studies accounting for sex differences in clinical trials, ensuring that treatments like Leqembi are more inclusive and effective across diverse populations.

Addiction

A New Approach to Reducing College-Aged Drinking Harms: Counter-Attitudinal Advocacy (CAA) Shows Promise

Researchers have developed and tested an intervention called Counter-Attitudinal Advocacy and compared it to to the well-established Personalized Normative Feedback (PNF) to evaluate their effectiveness in decreasing drinks per week, peak blood alcohol concentration and alcohol-related consequences relative to a control group.

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The excessive consumption of alcohol among young adults, particularly college students, poses significant health risks and social consequences. Heavy drinking can lead to blackouts, academic underperformance, interpersonal problems, and secondhand consequences for those who don’t drink, such as interrupted study sessions or having to care for intoxicated peers.

Recently, researchers from Brown University School of Public Health developed an innovative intervention called Counter-Attitudinal Advocacy (CAA). This approach involves advocating for a position that contradicts a personally held attitude or behavior. In the context of college drinking, CAA targets positive perceptions of heavy drinking and the belief that alcohol is an essential part of college life.

A randomized controlled trial at two sites involving 585 college students compared CAA to Personalized Normative Feedback (PNF), a well-established intervention. Researchers focused on drinks per week, a standard measure given the irregular drinking patterns of college students.

The results showed that participants who received PNF reported significantly fewer drinks per week than the control group, while those who received CAA reported significantly fewer consequences related to drinking. Notably, CAA had a harm reduction effect on consequences but not on consumption of alcohol, which it did not target.

According to co-lead investigator Kate Carey, “Both interventions take just 5-10 minutes, making them ideal for broad prevention efforts.” Carey emphasized that PNFs show participants how their drinking habits stack up against those of their peers, often exposing a common misconception that others drink more than they actually do. In contrast, CAA encourages participants to reflect on why it is a good idea to avoid alcohol-related problems and identify specific actions to minimize these risks.

CAA’s personalized approach frames the discussion broadly, focusing on why young people should avoid problems rather than directly telling them what to do. This makes the intervention more engaging and less confrontational. As participants respond to prompts, a research assistant or peer asks them to explain their written responses, which likely strengthens the intervention’s effect.

The researchers stress that having multiple brief interventions is essential since no single approach works for everyone. Offering evidence-based options increases the chances of reaching more people who are undergoing a period of heightened risk. With CAA providing another effective tool, especially for those who may not respond to PNF, this new approach holds promise in reducing college-aged drinking harms.

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“The Lasting Impact: How Alcohol Abuse Damages Decision-Making and Brain Function”

For the first time researchers demonstrate in an animal how heavy alcohol use leads to long-term behavioral issues by damaging brain circuits critical for decision-making.

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The Lasting Impact: How Alcohol Abuse Damages Decision-Making and Brain Function

For the first time, researchers have demonstrated in an animal study how heavy alcohol use leads to long-term behavioral issues by damaging brain circuits critical for decision-making. The findings, published in Science Advances, provide a new explanation of alcohol’s long-term effects on cognition.

The Study

In experiments led by research scientist Yifeng Cheng, rats were exposed to high amounts of alcohol for a month. After a nearly three-month withdrawal period, the rats were given a reward-based decision-making test along with a control group that had not been exposed to alcohol. The test was designed to be challenging, requiring memory and strategy to get the most reward.

The Results

The results showed that the alcohol-exposed rats performed considerably worse than the control group. This was due to dramatic functional transformations in the dorsomedial striatum, a part of the brain critical for decision-making. The researchers found that the alcohol had damaged neural circuits causing the rats to process information less effectively.

Long-Term Effects

One surprise was how long alcohol dependence impairs cognition and neural function, even after withdrawal. This may give us insight into why relapse rates for people addicted to alcohol are so high. “Alcohol-induced neural deficits may contribute to decisions to drink even after going to rehab,” said author Patricia Janak.

Future Directions

The researchers next hope to explore how alcoholism affects other areas of the brain that interact with the dorsomedial striatum, and what might be causing the differences between males and females. The study only found behavioral and neural impairments in male rats, but this does not suggest that female rats are immune from the effects of alcohol.

Conclusion

The findings of this study have important implications for our understanding of how alcohol abuse affects brain function and decision-making. By exploring these mechanisms further, we may be able to develop more effective treatments for addiction and improve outcomes for those struggling with substance use disorders.

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Addiction

Can Digital Games Help Adolescents Kick Bad Habits?

For adolescents struggling with substance abuse, traditional in-person interventions such as counseling are not always effective, and rural areas often lack access to these services. A researcher is thinking outside the box, aiming to help game designers develop fun, digital games that make ditching bad habits easier by meeting adolescents where they already are: online.

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The struggle with substance abuse is a reality many adolescents face. Traditional in-person interventions like counseling may not be effective for everyone, and rural areas often lack access to these services. Mansoo Yu, a researcher at the University of Missouri, is thinking outside the box to help game designers develop fun digital games that make ditching bad habits easier.

Yu analyzed 26 studies on digital interventions, including online games, virtual reality experiences, mobile app games, and video games, to identify the key elements that make these interventions effective in helping adolescents reduce drinking, smoking, and illicit drug use. His findings suggest that personalized games with social components for users to compete against friends and family, and content encouraging behavior change, are the most effective.

The research provides a blueprint for designing digital game-based interventions that can help adolescents reduce substance abuse and encourage positive development. Yu emphasizes the importance of meeting people where they already are – online. This approach increases accessibility in rural areas where in-person clinics and counseling services may not be available.

Unhealthy behaviors like smoking often serve as a way to cope with underlying mental health issues, including anxiety and depression. Therefore, successful digital game-based interventions should emphasize positive activities that can serve as alternatives to unhealthy behaviors. Yu suggests providing resources about healthier alternatives, such as sports, mentorship programs, music, painting, outdoor activities, or recreation centers.

Games that begin by asking for the user’s specific interests can create more personalized interventions, increasing user engagement. Yu hopes his research will help game designers develop customized and effective interventions to address substance abuse among adolescents.

Yu’s collaboration with colleagues from Ewha Womans University in South Korea led to a systematic review published in the international journal Children, titled “Game-based digital interventions for enhancing positive development and addressing substance use in adolescents.” This study aims to advance understanding of how digital games can be used as an effective intervention to help adolescents reduce substance abuse.

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