Daily Archives: 30 August 2024

Uncertain Impact of New Alzheimer’s Medications on Population Health, Researchers Indicate

Researchers from Cambridge have raised concerns about the efficacy of new amyloid immunotherapy drugs in significantly reducing the impact of Alzheimer’s disease. Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the team from Cambridge Public Health highlights several significant hurdles that could curtail the benefits of these treatments. These include a questionable risk-benefit ratio, limited patient eligibility, and the substantial costs of widespread implementation. Alzheimer’s disease accounts for approximately 70% of the 55 million dementia cases globally, though its precise definition remains contentious. A hallmark of the disease is the accumulation of amyloid proteins, which form plaques in the brain. According to the cascade hypothesis, which is a leading theory, this accumulation triggers a series of events that culminate in dementia symptoms.

The development of treatments aimed at reducing these symptoms and slowing the disease’s progression has been sluggish. However, recent breakthroughs in amyloid immunotherapy involving using the immune system to clear amyloid plaques have generated significant interest. Results from two completed phase III randomised controlled trials showed that these drugs could reduce the rate of cognitive and functional decline. However, the reductions were statistically significant but clinically minimal. Despite these findings, the Cambridge researchers point out that the differences in decline between patients on the drug and those on placebo were minimal, making it difficult for physicians to discern any real advantage after 18 months. Moreover, the trials revealed severe side effects such as brain swelling and bleeding. In one study of the drug donanemab, three deaths were attributed to the treatment.

The long-term impacts of these drugs, beyond the duration of the trials, remain largely unknown. Long-term placebo-controlled trials would be challenging, particularly as some drugs have already been approved. The US Food and Drug Administration has approved two such drugs. At the same time, the European Medicines Agency has recommended against approving one (lecanemab) due to the marginal benefits not outweighing the risks. The UK’s Medicines and Healthcare Products Regulatory Agency is poised to decide on these drugs.

Edo Richard, a professor of neurology at Radboud University Medical Centre in the Netherlands and co-author of the study, expressed concern about the enthusiasm surrounding these drugs. He stressed the importance of providing balanced information to help patients make informed decisions, especially given the desperation many feel when facing early-stage Alzheimer’s. Media reports suggest these drugs are suitable for all Alzheimer’s patients; however, the trials only included participants with early symptomatic Alzheimer’s and excluded those with other contributing conditions. These trial participants represent a tiny fraction—less than 8%—of the early Alzheimer’s population typically seen in health services, who are usually a decade or more older.

Dr Sebastian Walsh, NIHR Doctoral Fellow in Public Health Medicine at Cambridge Public Health and lead author, noted that even if approved, the drugs would only be suitable for a small subset of Alzheimer’s patients. Potential users would need extensive assessments before gaining access, and the benefits observed in trials were minimal. Effective administration would require identifying and treating patients at the earliest stages of the disease when symptoms are mild, a process that can be difficult.

The logistical and resource challenges of deploying such treatments are formidable. Even if the drugs are approved for a limited number of patients, many more would need assessments to determine their eligibility. This requirement would place additional strain on already stretched health services. Professor Carol Brayne, Co-director of Cambridge Public Health, highlighted the difficulty of rolling out these treatments on a large scale, even in high-income countries, and pointed out that most dementia occurs in low- and middle-income countries, where resources are even scarcer.

She also mentioned the potential for a more significant impact from addressing inequalities and health experiences throughout life, noting that the complexity of dementia often extends beyond a single protein issue. The team concludes that the current evidence does not support the use of amyloid immunotherapy in significantly reducing the suffering caused by dementia at a community level. As such, ongoing research into alternative approaches remains critical. With the global population ageing, finding effective support mechanisms for those living with dementia is more urgent than ever. Still, the promise shown by amyloid immunotherapies for select groups is insufficient to tackle the broader risk of dementia.

More information: Sebastian Walsh et al, Considering challenges for the new Alzheimer’s drugs: Clinical, population, and health system perspectives, Alzheimer s & Dementia. DOI: 10.1002/alz.14108

Journal information: Alzheimer’s & Dementia Provided by University of Cambridge

Research indicates that hepatitis E could be transmitted sexually

Leave a Reply

A new study conducted by researchers at Ohio State University has uncovered that the hepatitis E virus (HEV), found associated with sperm in pigs, might indicate that the virus could be transmitted sexually and may be linked to male infertility. HEV is primarily recognized as the leading cause of acute viral liver infections in humans globally, particularly prevalent in regions with poor sanitation. Interestingly, in the United States, the virus is endemic among pigs, residing primarily in organs rather than muscle tissue, and can be eliminated by cooking the meat thoroughly.

Given the associations between HEV and severe complications during pregnancy, as well as instances of male infertility in less developed areas, the research team explored the virus’s behaviour in pigs due to their reproductive anatomy’s resemblance to that of humans. After introducing HEV to pigs, the study observed that the virus circulated in the bloodstream and was excreted in faeces, suggesting that the pigs were infected but exhibited no clinical symptoms. This condition is often asymptomatic in humans as well. Crucially, the researchers discovered HEV on the heads of sperm cells, which could infect and replicate within human liver cells in laboratory settings.

Kush Yadav, the study’s lead author and a PhD student at Ohio State’s Center for Food Animal Health, highlighted the significance of their findings, stating, “This is the first study to demonstrate an association of the hepatitis E virus with sperm cells. Our future research will focus on understanding this relationship more deeply and determining through further animal model studies whether sexual transmission of the virus occurs, as its presence in human settings remains uncertain.” This groundbreaking research was recently published in the journal PLOS Pathogens, shedding light on a potentially new route of HEV transmission.

Sexually transmitted organisms, including HEV, can find a protective environment in the testicles, shielded by a blood-testis barrier that immune cells cannot breach. In addition to reproductive disorders, HEV is also suspected to cause pancreatic and neurological disorders in humans. Historically, HEV infections, even among pregnant individuals, were thought to be solely due to fecal-oral transmission routes.

The study also employed fluorescence microscopy to investigate pig semen 84 days after HEV inoculation, where Yadav detected viral particles on approximately 19% of the sperm cells collected from the infected pigs. He noted, “It’s unclear whether the viruses are on the outside or inside of the sperm cells or if hepatitis E can complete a replication cycle in the sperm head, so it appears sperm may be more of a carrier rather than a susceptible cell.” This discovery also showed a correlation between the presence of HEV and sperm damage, which could alter their structural integrity and decrease their motility, potentially leading to fertility issues.

Scott Kenney, an associate professor of veterinary preventive medicine and Yadav’s supervisor, emphasized the broader implications of their findings, suggesting that “Between 20 and 50% of male infertility cases remain unexplained. Hence, we are advocating for more extensive screening for the hepatitis E virus as a potential cause for these cases.” Additionally, the results of this study suggest that sexual partners of pregnant women who test positive for HEV should also be screened. However, the evidence for sexual transmission in humans has yet to be established conclusively.

Moreover, these findings have significant implications for the swine industry, where most pig litters are produced through artificial insemination, and donor sperm is distributed widely from extensive breeding facilities. Kenney remarked, “This could be part of the problem with HEV being endemic across the country and raises questions about whether it causes a reduction in the reproductive capacity of the pigs. While HEV doesn’t cause enough damage to pigs to limit production profitability, if we could implement some cost-effective screening or vaccination at these upstream boar facilities, maybe we could reduce the introduction of the virus into new herds.” This research opens new avenues for understanding HEV transmission and its broader impact on human and animal health.

More information: Kush K. Yadav et al, Infectious hepatitis E virus is associated with the mature sperm head, PLoS Pathogens. DOI: 10.1371/journal.ppat.1012240

Journal information: PLoS Pathogens Provided by Ohio State University

Regular Exercise of 2-3 Sessions Weekly Significantly Reduces Current Risk of Insomnia

Leave a Reply

Regular engagement in exercise, occurring 2-3 times weekly over a decade, correlates with a decreased risk of current insomnia and enhances the likelihood of achieving the advisable 6-9 hours of sleep nightly, as detailed in a comprehensive 10-year international study published in the open access journal BMJ Open. This study reinforces the well-established link between regular physical activity and improved overall health, highlighting that exercise not only enhances sleep quality but could also alleviate symptoms of chronic insomnia. The analysis, however, noted that the impact of variables such as gender, age, body mass index (BMI), overall fitness levels, general health, and the type of exercise on this relationship remains somewhat ambiguous.

The researchers left no stone unturned in their quest to understand the relationship between exercise and sleep. They meticulously assessed weekly exercise frequency, duration, and intensity, along with symptoms of insomnia, actual sleep duration, and daytime sleepiness among middle-aged adults across 21 centres in nine European countries. Drawing participants from the European Community Respiratory Health Survey, the study included 4399 individuals (2085 men and 2254 women) who provided data on their physical activity habits at the start (ECRHS II; 1998-2002) and ten years later (ECRHS III; 2011-2014). They also provided information on insomnia symptoms using the Basic Nordic Sleep Questionnaire, sleep duration, and daytime sleepiness assessed by the Epworth Sleepiness Scale.

Among the participants, 37% remained inactive over the ten years, 18% became active, 20% became inactive, and 25% consistently engaged in physical activity. Notably, participants in Norway exhibited the highest rates of consistent activity, whereas those in Spain and Estonia showed the highest inactivity rates. Consistently active participants typically were younger men with slightly lower body weight who were less likely to smoke and more likely to be employed.

After adjusting for factors like age, gender, BMI, smoking status, and location, those consistently active were significantly less likely to experience difficulties in falling asleep by 42%, showed a 22% reduced risk of any insomnia symptoms, and had a 40% lower likelihood of reporting multiple insomnia symptoms. Moreover, other factors such as age, being female, and higher body weight were also independently linked to insomnia symptoms.

Regarding total nightly sleep hours and daytime sleepiness, after adjustments, those who were consistently active were more likely to maintain regular sleep patterns. In contrast, those persistently inactive were more likely to experience disrupted sleep. Specifically, consistently active individuals were 55% more likely to be normal sleepers and significantly less likely to experience extremely short (less than 6 hours) or long (more than 9 hours) sleep durations. Meanwhile, those who transitioned from inactive to active status showed a 21% improvement in achieving standard sleep patterns compared to those who remained inactive.

Despite some limitations, including the inability to objectively measure changes in physical activity levels between the two-time points and reliance on self-reported data, the study’s findings have practical implications for individuals struggling with insomnia. The researchers concluded that consistent physical activity has a beneficial effect on insomnia symptoms, underscoring the importance of maintaining exercise habits over time. This aligns with previous research that emphasizes the positive effects of physical activity on insomnia symptoms, providing individuals with actionable insights to improve their sleep quality.

More information: Erla Bjornsdottir et al, Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study, BMJ Open. DOI: 10.1136/bmjopen-2022-067197

Journal information: BMJ Open Provided by BMJ Group

Consuming Entire Small Fish May Extend Lifespan, According to Japanese Research

Leave a Reply

A study conducted by Dr. Chinatsu Kasahara alongside Associate Professor Takashi Tamura and Professor Kenji Wakai at the Nagoya University Graduate School of Medicine in Japan has uncovered compelling evidence that links the consumption of small fish, eaten whole, with a notable reduction in mortality from all causes and cancer, particularly in Japanese women. The research, published in Public Health Nutrition, explores the life-extending benefits of regularly consuming small fish such as whitebait, Atlantic capelin, Japanese smelt, and small dried sardines. These fish are typically eaten whole, including their heads, bones, and organs, providing a rich source of micronutrients like calcium and vitamin A.

Dr. Kasahara, the study’s lead researcher, mentioned that the protective effects of fish consumption on health and mortality risks are well-documented. Yet, few studies have focused explicitly on the impact of small fish consumption on health outcomes. Driven by a lifelong personal practice of eating small fish—a habit she now passes on to her children—Dr. Kasahara was mainly motivated to investigate this area further.

The study encompassed a large cohort of 80,802 Japanese individuals, comprising 34,555 men and 46,247 women aged between 35 and 69, from various regions across Japan. At the study’s outset, participants’ frequency of small fish consumption was meticulously gauged using a food frequency questionnaire. Over an average follow-up period of nine years, the researchers recorded 2,482 deaths, of which around 60% (1,495 deaths) were attributed to cancer.

Among the study’s key findings was the significant decrease in all-cause and cancer-related mortality observed among women who regularly consumed small fish. Women who ate small fish once to three times a month, one to two times a week, or three times or more per week experienced 0.68, 0.72, and 0.69 times the risk of all-cause mortality, respectively, and 0.72, 0.71, and 0.64 times the risk of cancer mortality compared to those who seldom ate small fish.

After adjusting for potential confounding factors such as age, smoking and alcohol habits, BMI, and other dietary nutrients and foods, it became clear that women who frequently consumed small fish had a lower likelihood of dying from any cause. These findings advocate for integrating small fish into daily diets as a straightforward yet potent strategy to enhance longevity in women.

Conversely, while a similar trend was observed in men, the results were not statistically significant. The researchers speculated that this could be due to a smaller sample size among men or other unmeasured factors, such as the portion sizes of small fish consumed. They also considered that differences in the types of cancer-causing mortality between the sexes might reflect a gender-specific association.

Despite these promising results being specific to the Japanese population, Dr. Kasahara believes these findings have broader implications. She expressed enthusiasm about the potential relevance of their findings to other nationalities. She highlighted the need for further research to explore the mechanisms underlying these associations and to validate these findings in different populations.

Furthermore, the study reiterates the importance of small fish as an affordable and nutrient-rich food source, particularly in developing countries where nutrient deficiencies are prevalent. Dr Kasahara emphasised the unique nutrients and physiologically active substances found in small fish that could be crucial in maintaining health, underscoring the inverse relationship between small fish intake and mortality risk in women.

Associate Professor Tamura noted that while eating small fish is generally limited to coastal or maritime nations like Japan, there is a growing suspicion that it could universally extend life expectancy. However, additional evidence is needed to fully understand the potential role of small fish intake in reducing mortality risk.

More information: Chinatsu Kasahara et al, Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study, Public Health Nutrition. DOI: 10.1017/S1368980024000831

Journal information: Public Health Nutrition Provided by Nagoya University