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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

The Seasons’ Influence on Your Body: How Time Affects Tolerance, Weight Gain, and More

Researchers have found that drug effectiveness, alcohol tolerance, and carbohydrate metabolism change with the seasons. Their findings are based on a comprehensive seasonal gene expression map, which investigated over 54,000 genes in 80 tissues in monkeys across one year. The study has implications for drug prescription and precision medicine.

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As we navigate through the changing seasons, our bodies undergo subtle yet significant changes that can impact our tolerance to medication, weight gain, and even alcohol consumption. Researchers from Nagoya University in Japan have made a groundbreaking discovery by creating a comprehensive seasonal gene expression map, which analyzed over 54,000 genes in 80 tissues of monkeys across one year.

The study, published in Nature Communications, reveals that our biological clock is calibrated to the seasons, influencing various physiological processes such as hormone secretion, metabolism, sleep patterns, immune function, and reproduction. The researchers identified multiple “seasonally variable genes” responsible for changes in drug metabolism, particularly affecting a quarter of common medications.

These seasonal fluctuations can impact treatments for cancer, diabetes, high cholesterol, psychiatric conditions, hormonal therapies, and immunosuppressants used in organ transplantation. Moreover, the study found that mice reared under winter conditions recovered from alcohol intoxication more quickly than those reared under summer conditions.

Interestingly, women’s bodies show a different pattern of carbohydrate metabolism compared to men’s, peaking during winter and spring in the duodenum. This increased energy extraction is essential for survival during scarce food periods, which may explain why people often gain weight during these times.

The findings suggest that chronotherapy – tailoring treatments to specific seasonal conditions – may revolutionize our responses to various health issues. By considering the time of year when administering medications, we can better address the dynamic changes in human physiology and behavior throughout the seasons.

As Professor Takashi Yoshimura said, “Our research will contribute to chronotherapy and the future of precision medicine.” This exciting discovery opens up new avenues for personalized treatment approaches, taking into account the intricate relationships between our genes, environment, and body’s responses.

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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 article you provided is well-structured and easy to follow. However, I made some minor changes to improve clarity and flow:

* Added a brief summary at the beginning to set the context for the reader.
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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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