Monthly Archives: August 2024

University of Hawaii Study Reveals Faster Biological Aging Among Native Hawaiians

In a study from the University of Hawaiʻi at Mānoa, researchers have uncovered that Native Hawaiians exhibit a higher rate of accelerated biological ageing compared to White and Japanese American residents. The study also highlights the impact of living in adverse environments, such as neighbourhoods with low socioeconomic status, contributing to accelerated biological ageing regardless of ethnic background. However, life experiences might provide a buffer against this acceleration.

The research led by Alika Maunakea, a Native Hawaiian professor of epigenetics and a researcher in health disparities at the John A. Burns School of Medicine, indicates that individuals residing in socioeconomically disadvantaged areas can mitigate some of the effects of accelerated ageing. Those who participate in regular physical activity, achieve higher educational levels, and maintain healthier diets appear to experience biological ageing rates more aligned with their chronological age. These factors were associated with a lower BMI and a reduced risk of diabetes.

The study delved into cancer research data to establish these findings. Maunakea and his team analyzed DNA samples from 376 participants in the UH Cancer Center’s ongoing multiethnic cohort. Biological ageing is considered the progressive decline in cellular and physiological functions, reflecting the body’s actual age on a molecular and cellular level, which can differ from chronological age. This type of ageing is assessed through DNA methylation, an epigenetic process that influences gene activity and indicates biological age. This process allows scientists to determine whether an individual is ageing faster or slower than their chronological age.

While previous research on DNA methylation and biological age has primarily focused on populations of European ancestry, studies on ethnically diverse populations have been limited. This gap is significant as these populations often experience higher incidences and earlier onsets of diseases such as diabetes, heart disease, and certain cancers, particularly evident in Native Hawaiians. This group also suffers from the highest all-cause mortality rates compared to other major ethnic groups in Hawaiʻi. Through this study, Maunakea hopes to illuminate the biological mechanisms underlying health disparities in Native Hawaiians to address these issues better.

Maunakea emphasizes these findings’ substantial public health implications, suggesting that they could inform health policy. While it may be challenging to change certain neighbourhood-level factors affecting health, such as residential location and environmental conditions, individual lifestyle choices related to education, physical activity, and diet can be enhanced through federal, state, and community initiatives. One such example is MAʻO Organic Farms in Waiʻanae, which combats health and socioeconomic disparities in the region.

Reflecting on the personal significance of the study’s outcomes, Maunakea, born and raised in Waiʻanae, views the results as confirmation that lifestyle plays a crucial role in health. He argues that being Native Hawaiian does not predetermine one’s health trajectory, even in economically challenged areas. The molecular data from the study demonstrates that adopting healthier lifestyles reduces disease risk and likely enhances longevity. This insight gives Maunakea hope for significant improvements in health and well-being for Native Hawaiians within his lifetime.

More information: Alika K. Maunakea et al, Socioeconomic Status, Lifestyle, and DNA Methylation Age Among Racially and Ethnically Diverse Adults, JAMA. DOI: 10.1001/jamanetworkopen.2024.21889

Journal information: JAMA Provided by University of Hawaiʻi at Mānoa

Public Health Initiatives Aimed at Reducing Dementia Risk Could Potentially Save the UK Economy Up to £4 Billion

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Public health interventions aimed at reducing dementia risk factors could potentially save up to £4 billion in England by lowering dementia rates and enhancing overall health and longevity, according to recent findings by researchers from University College London (UCL).

The findings, published in The Lancet Healthy Longevity, indicate that various interventions—such as reformulating food products to decrease sugar and salt consumption, implementing low emission zones to improve urban air quality, and introducing minimum pricing per unit of alcohol to curb consumption—could yield significant benefits beyond their direct health impacts.

Dr Naaheed Mukadam from UCL Psychiatry, the study’s lead author, stated, “Extensive research suggests that dementia incidence could be reduced by addressing risk factors throughout a person’s life. Numerous risk factors, including smoking, alcohol consumption, and high blood pressure, increase the likelihood of developing dementia later in life and can be effectively mitigated through public health strategies. Although many of these initiatives aim not to reduce dementia, their substantial impact on dementia risk suggests that they could be financially justifiable by the savings in dementia-related costs alone, which should be a routine consideration in cost-benefit analyses.”

The economic modelling conducted in the study assessed the potential impact of population-wide interventions on dementia rates and associated costs, projecting over 70,000 gains in Quality Adjusted Life Years (QALY) across the population. These interventions targeted six key risk factors: smoking, alcohol use, obesity, hypertension, head injuries, and air pollution.

A prior study in 2022, also co-authored by Dr Mukadam, established that various interventions targeting such risk factors are cost-effective without even accounting for their impact on dementia by reducing costs associated with other health issues like hypertension and diabetes. The latest research further suggests that these interventions become even more cost-effective when factoring in the costs associated with dementia.

In their examination of public health strategies, the researchers estimated that modifying food products to reduce salt and sugar intake could save £2.4 billion and £1.1 billion and achieve QALY gains of 39,433 and 17,985, respectively. Additionally, a 10% hike in cigarette prices could save £157 million in dementia-related costs, and mandating bicycle helmets for children could prevent head injuries, potentially saving £91 million in dementia costs in the future.

Dr. Mukadam’s earlier 2020 study found that individual measures like hearing aids, nicotine gum for smoking cessation, or medication to manage high blood pressure could annually save £1.9 billion in England.

This latest research aligns with the findings from the third Lancet Commission on dementia prevention, intervention, and care, led by Professor Gill Livingston of UCL Psychiatry, which posits that nearly half of dementia cases could be prevented or delayed by addressing 14 risk factors throughout life.

Professor Livingston, the senior author of the economic modelling paper, noted, “While the quest for effective dementia treatments is a significant challenge for scientists, clinicians, and governments, there is hope. Moreover, we can prevent many instances of dementia by targeting risk factors early. As the population ages and the societal costs of dementia escalate, the need for public health measures to prevent dementia becomes increasingly urgent.”

Dr. Mukadam further emphasized the need for policy-based approaches that alleviate individual responsibility, stating, “People can reduce their own risk of dementia through lifestyle changes, but effective public policies are essential. These interventions, while initially costly, more than pay for themselves over time by reducing future health and social care expenses. Studies suggest that such interventions could be particularly impactful in reducing health disparities in low- and middle-income countries or among lower-income groups, thereby improving the health of the entire population.”

Samantha Benham-Hermetz, Executive Director of Alzheimer’s Research UK, also highlighted the economic and societal toll of dementia, noting the staggering costs and doubling hospital expenditures over the past decade primarily due to emergency admissions. With an ageing population, these costs are set to rise further. She pointed out, “Up to 45% of dementia cases are preventable, and there are cost-effective public health measures available that could significantly reduce the risk of dementia. This presents a dual opportunity for the government to extend healthy life expectancy while optimizing the use of public funds.”

More information: Naaheed Mukadam et al, Benefits of population-level interventions for dementia risk factors: an economic modelling study for England, The Lancet Healthy Longevity. DOI: 10.1016/S2666-7568(24)00117-X

Journal information: The Lancet Healthy Longevity Provided by University College London

Study: Diabetes and Weight-Loss Drugs Halve Risk of Alcohol-Use Disorder

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A recent study conducted by researchers at Case Western Reserve University School of Medicine suggests that semaglutide, a medication commonly used in widespread diabetes and weight-loss drugs Wegovy and Ozempic, may significantly decrease the incidence and recurrence of alcohol abuse or dependence. Published in Nature Communications, this research underscores a potentially innovative treatment avenue for alcohol-use disorder (AUD) — a condition responsible for approximately 178,000 deaths annually in the US, as per the Centers for Disease Control.

The study delved into the electronic health records of almost 84,000 patients with obesity, discovering that those treated with semaglutide exhibited a 50% to 56% reduction in the onset and recurrence of AUD over the following year, compared to patients treated with other anti-obesity drugs. This impressive outcome highlights semaglutide’s role as a glucagon-like peptide-1 receptor agonist (GLP-1), which not only helps manage blood sugar levels in type 2 diabetes and curb appetite.

Rong Xu, the study’s lead researcher and a professor of biomedical informatics at the School of Medicine, expressed optimism about the results. Xu, the director of the Center for AI in Drug Discovery at the medical school, worked alongside Nathan Berger, the Hanna-Payne Professor of Experimental Medicine, and Pamela Davis, the Arline H. and Curtis F. Garvin Research Professor. Nora D. Volkow, director of the National Institute for Drug Abuse, also contributed to the study.

Berger noted the methodological consistency with the team’s earlier studies this year, which showed semaglutide’s associations with reduced suicidal thoughts and a decrease in both new diagnoses and recurrence of cannabis-use disorder. These findings were echoed in a subsequent review of electronic health records for around 600,000 patients with type 2 diabetes, further supporting the link between semaglutide treatment and reduced diagnoses of AUD.

Despite the promising data, Davis emphasised the need for further randomised clinical trials to establish semaglutide’s clinical utility for treating AUD comprehensively. The current findings provide preliminary real-world evidence pointing towards the potential benefits of semaglutide for managing AUD, marking a significant step forward in the search for effective treatments for this pervasive health issue.

More information: William Wang et al, Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population, Nature Communications. DOI: 10.1038/s41467-024-48780-6

Journal information: Nature Communications Provided by Case Western Reserve University

Alcohol Consumption in Elderly Doubles Risk of Brain Hemorrhage Due to Falls

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Falls are the leading cause of both fatal and non-fatal injuries in older adults across the United States, also topping the charts for traumatic brain injuries. In 2021 alone, falls claimed the lives of 36,500 older Americans and 3,805 older residents of Florida. Research into the potential link between alcohol use and the severity of these incidents is limited, but existing studies suggest a possible connection. The scarcity of detailed investigations into how alcohol consumption affects the likelihood and severity of falls highlights a significant gap in our understanding of this issue.

Recognizing this knowledge gap, Florida Atlantic University’s Schmidt College of Medicine, in collaboration with other researchers, initiated one of the first studies to analyze the correlation between self-reported alcohol use and the incidence of severe head trauma among older individuals. Utilizing data from the Geriatric Head Trauma Short Term Outcomes Project (GREAT STOP), which tracked a cohort of patients aged 65 and older who sustained blunt head trauma from falls at two major trauma centers, the study involved over 3,000 participants. Researchers found that 433 (13.5%) suffered intracranial haemorrhage (ICH), with 561 (18.2%) reporting alcohol consumption.

The results revealed a troubling link between alcohol use and increased risk of ICH. Richard Shih, M.D., the study’s corresponding author and a professor of emergency medicine at FAU, noted that occasional alcohol consumption doubled the odds of ICH compared to non-drinkers. In contrast, daily consumption increased the odds by 150%. The study also demonstrated a clear dose-response relationship between the frequency of alcohol use and the incidence of ICH, with more frequent drinkers facing significantly higher risks.

Demographically, the study observed that alcohol users who suffered head traumas tended to be younger, averaging 78 years, compared to non-users who averaged 83 years. The prevalence of ICH was markedly higher in alcohol users (22%) compared to non-users (12%), and the risk escalated with increasing alcohol consumption. The absolute risk differences associated with alcohol use were substantial, showing a marked increase from occasional to daily drinkers.

Several risk factors for falls have been identified in older adults, including polypharmacy, sudden drops in blood pressure, and unsafe home environments. Shih’s study suggests that alcohol consumption should also be considered a significant, independent, and modifiable risk factor. He explained that alcohol affects balance, concentration, and awareness, thus increasing the likelihood of falls. Additionally, as individuals age, their ability to metabolize alcohol diminishes, compounded by a higher body fat-to-body water ratio, which results in a higher concentration of alcohol in the bloodstream.

Despite these findings, current fall prevention guidelines from entities like the Centers for Disease Control and Prevention’s STEADI initiative of the American Geriatrics Society do not currently address the relationship between alcohol use and falls. Shih advocates for the inclusion of alcohol use assessment and mitigation strategies in fall prevention protocols, stressing the need for comprehensive strategies that consider all significant risk factors to reduce the incidence of falls among older adults effectively.

More information: Alexander Zirulnik et al, Alcohol use is associated with intracranial hemorrhage in older emergency department head trauma patients, Journal of the American College of Emergency Physicians Open. DOI: 10.1002/emp2.13245

Journal information: Journal of the American College of Emergency Physicians Open Provided by Florida Atlantic University

Study Reveals Children May Develop Premature Aging Signs Due to Parental Alcohol Abuse

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Researchers at the Texas A&M School of Veterinary Medicine and Biomedical Sciences (VMBS) have unveiled compelling evidence that children of parents grappling with alcohol use disorders may inherit predispositions to premature ageing, with ramifications extending into their adult lives.

The manifestations of such accelerated ageing include severe conditions such as elevated cholesterol levels, cardiovascular issues, arthritis, and early-onset dementia. These health challenges can originate from either parent; however, the effects are notably exacerbated when both parents suffer from alcohol misuse, particularly affecting male children.

Dr. Michael Golding, a distinguished professor in the Department of Veterinary Physiology and Pharmacology at VMBS, explained the underlying concerns that have puzzled scientists for years: why do children from alcohol-affected homes have a higher propensity to fall ill? “These children often exhibit behavioural challenges, struggle with stress management, and frequently encounter conflicts with educational and legal authorities,” Golding noted.

Until now, the debate centred around whether the root cause of such early ageing and increased disease susceptibility was environmental stress or a hereditary factor from the parents. Golding clarified, “It has become clear that these children inherit mitochondrial dysfunction as a direct consequence of their parents’ alcohol abuse. This dysfunction precipitates early signs of age-related diseases, typically manifesting in their forties.”

With this new knowledge, Golding is optimistic that medical professionals can intervene more effectively, enhancing mitochondrial health through lifestyle modifications such as physical activity and dietary improvements, potentially mitigating the inherited dysfunctions as individuals age.

The study also delves into the broader implications of alcohol on ageing, mainly focusing on a biological phenomenon known as senescence—where cells diminish in function and cease to divide, impairing the body’s ability to rejuvenate itself. “Senescence is particularly critical in brain health, leading to cognitive decline and memory issues,” added Golding. Long-standing evidence suggests that excessive alcohol consumption accelerates senescence, particularly in adults.

Utilising a mouse model, Golding’s research has demonstrated that senescence is a prominent feature inherited by offspring from parents who consume alcohol up to or exceeding legal limits daily. “This condition is linked to increased fat deposition in the liver and subsequent scarring, a scenario that is markedly prevalent in male descendants when both parents are alcohol-dependent, significantly raising their risk of developing liver diseases,” he stated.

Focusing on the intricate biological connections between parental alcohol consumption and offspring development, Golding’s laboratory has also shed light on paternal influences on conditions like Fetal Alcohol Syndrome (FAS). Alongside continuing his advocacy for reduced alcohol intake among parents pre-conception, Golding highlighted the numerous developmental challenges children face due to FAS—ranging from physical abnormalities to behavioural and cognitive impairments.

The findings underscore not just the immediate impacts of parental drinking but also its prolonged effects on the ‘healthspan’ of children—defined as the duration of life spent in good health, free from chronic and debilitating diseases. “Understanding these multi-generational health impacts reveals that healthy living benefits can also be passed down, enhancing the quality of life for future generations,” Golding concluded. He advocates for potential parents to adopt healthier lifestyles pre-conception to benefit their children’s health from birth through adulthood significantly.

More information: Alison Basel et al, Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model, Aging and Disease. DOI: 10.14336/AD.2024.0722

Journal information: Aging and Disease Provided by Texas A&M University

Recent Research Emphasises Worldwide Inequalities in Mobility Restrictions and Utilisation of Assistive Technologies

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A recent investigation involving over 175,000 individuals across 25 nations has revealed that people in low—and middle-income countries encounter more significant challenges in their daily activities and are less inclined to use assistive devices than their counterparts in high-income countries. This revelation underscores concerns about the disproportionate global burden of disability, particularly prevalent in poorer regions.

Although global statistics show a decline in mortality and cardiovascular diseases, along with an extension in life expectancy, the health outcomes in less affluent nations remain substantially inferior to those in wealthier countries. The disparity in the prevalence of disabilities across various regions remains less explored. This pioneering prospective study surveyed participants on mobility, vision, and hearing limitations, discovering that such impairments are widespread, with mobility, bending, and visual challenges being the most common. Notably, one-third of the respondents reported experiencing at least one form of limitation, with older adults and women being the most affected groups.

The study revealed that limitations in daily activities are notably more prevalent in lower-income settings. Instances of walking and visual impairments are two and five times higher, respectively than in more affluent nations.

Raed Joundi, the study’s lead author and a researcher at the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences, emphasised the scarcity of comprehensive data on activity limitations and their impact globally. The study aimed to bridge this gap by examining the frequency of fundamental activity limitations, the adoption of assistive technologies, and the resultant health outcomes across 25 countries.

As part of the extensive Prospective Urban Rural Epidemiological (PURE) study led by PHRI and Salim Yusuf, the senior scientist, the research was published in The Lancet on July 25, 2024. It gathered data from individuals aged between 35 and 70 using standardised questionnaires and monitored them over an average of 11 years, extending up to 20 years in some cases.

The findings also highlighted that simple yet essential assistive devices such as canes or glasses could significantly alleviate the daily challenges faced by individuals with disabilities. However, in poorer nations, the use of such basic aids was less than half that observed in wealthier countries.

Yusuf stressed the critical importance of access to assistive devices in enhancing the quality of life and enabling individuals to reach their potential despite disabilities. He pointed out the significant gap in access as a pivotal area for health policy and intervention in low—and middle-income countries.

Moreover, the research linked mobility restrictions with severe health issues, including elevated risks of mortality, cardiovascular diseases, pneumonia, and falls, underlining the profound impact of activity limitations on health.

Joundi called for developing policies and programmes to ensure disabled individuals in less affluent countries access essential assistive devices and other resources necessary for maintaining health. He also advocated for a deeper understanding of the factors leading to these limitations and the formulation of public health strategies to prevent them, aiming for a future where individuals can enjoy longer, healthier, and more fulfilling lives.

More information: Raed A Joundi et al, Activity limitations, use of assistive devices, and mortality and clinical events in 25 high-income, middle-income, and low-income countries: an analysis of the PURE study, The Lancet. DOI: 10.1016/S0140-6736(24)01050-X

Journal information: The Lancet Provided by McMaster University

Research Reveals Adolescent Sports Boost Bone Health in Older Adults

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Loss of bone mineral density (BMD) as individuals age significantly contributes to osteoporosis—a degradation of bone tissue. In Japan, this deterioration is a primary cause of falls among older adults, leading to fractures and extended nursing care. Addressing osteoporosis in the ageing population can reduce disease prevalence and healthcare expenditures.

Lifestyle choices made early in life, particularly during adolescence, can profoundly impact health outcomes in later years. Engaging in physical activity during these formative years contributes to the accumulation of bone mass, which peaks in the 20s and then diminishes as one age. Research indicates that increasing peak bone mass by 10% during adolescence could postpone the onset of osteoporosis by as many as 13 years. Nevertheless, the specific types of sports activities during adolescence that benefit BMD and overall bone health in later life remain unclear.

Aiming to fill this knowledge gap, a team of researchers from Juntendo University in Japan has explored how different sports played during adolescence affect bone density in later years. Their findings were published in the 14th volume of ‘Frontiers in Physiology’ on 12 October 2023. The research team included Professor Yoshifumi Tamura of the Faculty of International Liberal Arts, alongside colleagues from the Sportology Center and the Department of Metabolism & Endocrinology at the Graduate School of Medicine.

Professor Tamura elaborated on their discoveries, noting the challenges in boosting BMD once it has declined and highlighted the crucial role of maximising bone mass during youth to sustain bone health into old age. Their research provides pivotal insights into how exercise in youth can prevent osteoporosis and supports the creation of early intervention strategies.

The study surveyed 1,596 elderly individuals aged 65 to 84 from the Bunkyo Health Study in Tokyo. Assessments included physical fitness tests, vitamin D levels, and BMD measurements of the femoral neck and lumbar spine using dual-energy X-ray absorptiometry. Participants were also interviewed about their involvement in sports during adolescence, and additional data on their health and lifestyle were collected.

Findings showed that while BMD levels in the femoral neck and lumbar spine were generally normal among men, women exhibited lower values, with a significant number on osteoporosis medication. The study also highlighted disparities in conditions like diabetes and lifestyle factors such as smoking and alcohol consumption between genders. Popular sports during the participants’ youth included baseball, basketball, judo, table tennis, tennis, volleyball, and swimming.

Basketball, in particular, was associated with higher femoral BMD in older adults and women, with body weight and vitamin D levels also influencing BMD. Women who had engaged in volleyball and swimming showed higher lumbar spine BMD, though no sports were linked to lumbar spine BMD in men. Factors such as body weight, vitamin D levels, and diabetes presence were also important.

The results suggest that engaging in high-impact sports during adolescence leads to better bone density and health in later life, with benefits extending beyond athletes to the general population who participated in sports during their school years.

This underscores the significance of encouraging impactful sports activities in schools, as early sporting engagement can lay the groundwork for robust bone health throughout life. “Engaging in physical exercise during adolescence has long-term benefits on BMD, extending over fifty years into older age,” concluded Professor Tamura, emphasising the long-lasting impact of adolescent sports on health in later years.

More information: Hikaru Otsuka et al, Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study, Frontiers in Physiology. DOI: 10.3389/fphys.2023.1227639

Journal information: Frontiers in Physiology Provided by Juntendo University Research Promotion Center

Chances of Anxiety and Suicide Attempts Could Increase Substantially Following Hospitalization for Heart Issues

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In an enlightening study published in the Journal of the American Heart Association, it was discovered that individuals hospitalized for heart disease, stroke, or other cardiovascular conditions are significantly more likely to be diagnosed with mental health issues such as anxiety, depression, and suicidal behaviours within the first year post-discharge, compared to those without cardiovascular disease. The research, led by Huan Song, M.D., PhD, a professor of epidemiology at the West China Biomedical Big Data Center at West China Hospital, Sichuan University in Chengdu, China, highlights the essential link between physical and mental health following such diagnoses. Unlike previous studies, this analysis incorporated environmental and lifestyle factors. It examined the effects of genetic predispositions on the relationship between cardiovascular and psychiatric conditions, using data from the UK Biobank—a large-scale biomedical database with health information from about 500,000 adults.

Cardiovascular conditions defined in the study included ischemic heart disease and cerebrovascular diseases such as stroke, blood clots, heart failure, and irregular heart rhythms. The analysis focused on the prevalence of psychiatric disorders diagnosed after hospitalization for these conditions, contrasting it with a control group matched for age, gender, and health status but free from prior cardiovascular or psychiatric conditions. The findings revealed an 83% increased likelihood of a psychiatric disorder diagnosis within a year of a cardiovascular-related hospital admission, with a sustained 24% increased risk extending nearly eight years after the event. Exceptionally high risks were noted for anxiety, depression, and suicidal behaviours, with those experiencing stroke or other cerebrovascular events facing more than three times the risk of psychiatric disorders within the first year and a 49% increased risk after that.

Mariell Jessup, M.D., FAHA, chief science and medical officer of the American Heart Association, emphasized the importance of integrating mental health care into cardiovascular patients’ treatment and recovery process. The findings affirm that after a cardiovascular diagnosis and hospitalization, patients face a higher risk for mental health issues, thus necessitating mental health screening and early intervention as critical components of patient care. Routine screenings and referrals for mental health services are recommended, aligning with the association’s guidelines for comprehensive care encompassing psychological and physical health.

Dr. Song also highlighted the necessity for individuals experiencing mental health difficulties post-cardiovascular events to seek immediate support. Healthcare professionals can provide valuable support and direct patients to mental health specialists or support networks essential for managing these challenges. It’s crucial for patients, families, and caregivers to be proactive in recognizing signs of mental distress and to communicate any changes to the healthcare team promptly.

However, the study acknowledges its limitations, such as the potential underrepresentation of less severe cardiovascular cases that did not require hospitalization and reliance on hospital admission data for cardiovascular diagnosis. Additionally, since the data primarily represents white British adults, the findings may not fully apply to other racial, ethnic, or geographic groups.

This comprehensive analysis underscores the intricate interplay between cardiovascular health and mental well-being, advocating for an integrated approach to patient care that addresses both dimensions to enhance overall patient outcomes. This approach not only aids in recovery but also supports long-term health management, highlighting the necessity for vigilant monitoring and intervention in the mental health of cardiovascular patients.

More information: Jie Yang et al, Cardiovascular Disease, Genetic Susceptibility, and Risk of Psychiatric Disorders and Suicide Attempt: A Community‐Based Matched Cohort Study Based on the UK Biobank, Journal of the American Heart Association. DOI: 10.1161/JAHA.123.031280

Journal information: Journal of the American Heart Association Provided by American Heart Association

Is the ‘Treat-All’ Approach for Chronic Hepatitis B Virus Infection in China Fully Implemented?

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Chronic hepatitis B (CHB) remains a significant public health issue, particularly in China, where the disease is prevalent. In response, the 2022 Chinese guidelines for the prevention and treatment of CHB have adopted a more aggressive stance, broadening treatment criteria and simplifying management protocols to improve overall disease control. This essay elaborates on Mengyang Zhang et al.’s study, published in the Journal of Clinical and Translational Hepatology, which assesses these new guidelines and evaluates the impact of a “Treat-all” strategy in managing CHB. The review begins by emphasising the substantial health burden of untreated CHB, which can progress to severe liver diseases like cirrhosis and hepatocellular carcinoma (HCC), particularly underlining the situation in China, where HBV is a major cause of liver-related death.

The “Treat-all” strategy outlined in the guidelines advocates for initiating treatment in all individuals with detectable HBV DNA or positive HBsAg, aiming to reduce the disease burden by preventing the progression to more severe liver conditions. The rationale is that early treatment can enhance quality of life, minimise infectivity, and manage comorbidities such as fatty liver disease and HBV reactivation in the context of immunosuppressive therapies. This approach supports evidence that early antiviral treatment can prevent the progression of liver disease and reduce the incidence of HCC, suggesting a significant shift towards proactive disease management.

The expanded criteria in the 2022 guidelines now recommend treatment for nearly all patients with detectable HBV DNA, mainly targeting those at higher risk of disease progression. This includes adults over 30, due to the increased risk of disease progression and HCC, and children aged 1-7, who have a higher chance of achieving a functional cure and present significant liver damage. Furthermore, treatment is advised for at-risk adults exhibiting symptoms like elevated ALT, cirrhosis, considerable fibrosis, extrahepatic manifestations, or a family history of HCC.

A central discussion point in the review is the treatment of patients with HBeAg-positive chronic HBV infection, which traditionally was not immediately treated due to perceived minimal liver damage. Recent studies challenge this view, showing significant histological damage even in this phase and suggesting that early antiviral treatment can prevent disease progression and reduce HCC risk. The article also stresses the cost-effectiveness of early treatment initiation, utilising decision-tree Markov models to demonstrate that expanding antiviral treatment to all HBsAg-positive patients could drastically reduce liver-related events and overall healthcare costs, aligning with WHO’s goals to decrease HBV-related mortality by 65%.

Despite the promising prospects of the “Treat-all” strategy, it also presents challenges such as the potential for overtreatment, the necessity for sustained adherence to antiviral therapy, and managing the risks associated with treatment withdrawal, like viral relapse and liver failure. The review calls for continued research and adaptation of treatment strategies to address these challenges and improve patient outcomes effectively.

The 2022 Chinese guidelines for CHB mark a significant advancement in the proactive management of chronic hepatitis B. By advocating a “Treat-all” approach, despite its associated challenges, there is a substantial potential to reduce the burden of HBV-related liver diseases and contribute to the elimination of hepatitis B as a public health threat by 2030. The insights provided by Mengyang Zhang et al. are crucial. They emphasise the importance of early treatment and explore both the benefits and challenges of a more inclusive antiviral treatment approach in the context of global health strategies.

More information: Mengyang Zhang et al, “Treat-all” Strategy for Patients with Chronic Hepatitis B Virus Infection in China: Are We There Yet? Journal of Clinical and Translational Hepatology. DOI: 10.14218/JCTH.2024.00091

Journal information: Journal of Clinical and Translational Hepatology Provided by Xia & He Publishing Inc.

Australians surpass their counterparts in affluent English-speaking nations by 1-4 years in lifespan

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A study published in the open-access journal BMJ Open reveals that Australians live longer than their counterparts in five other high-income English-speaking countries, including the UK and the US, with a lifespan advantage of 1 to 4 years. The analysis, which scrutinised international longevity data from 1990 to 2019, shows that most of Australia’s longevity benefits range from 45 to 84. Australians generally experience lower mortality rates from issues such as drug and alcohol misuse, treatable cancers, and cardiovascular and respiratory diseases.

Despite significant gains in life expectancy during the 20th century across high-income nations, progress has slowed markedly since the beginning of the 21st century. This slowdown, even before the disruptions caused by the COVID-19 pandemic, is concerning. Factors contributing to this include plateauing reductions in cardiovascular disease deaths and increases in fatalities related to drug overdoses, mental health issues, and neurological conditions. Furthermore, the disparity in life expectancy between the wealthiest and poorest segments of these countries has expanded over recent years, highlighting the issue of inequality.

The researchers aimed to explore differences in lifespan among six affluent English-speaking countries: Australia, Canada, Ireland, New Zealand, the UK, and the USA, representing some of the most prosperous global economies. They utilised national life tables from the Human Mortality Database and detailed mortality data by age, sex, and cause from the World Health Organization Mortality Database to assess these disparities.

The study’s key findings reveal that Australia consistently outperformed its peers in terms of life expectancy at birth from the early 1990s onwards. Australian women led by 1.26 to 3.95 years and men by 0.97 to 4.88 years as of 2018. Notably, Australia had a significant 4 to 5 year life expectancy advantage over the USA and a 1 to 2.5 year advantage over the other mentioned countries.

Canada generally held the second-highest life expectancy throughout the observed period, recently matched by Ireland and New Zealand. However, the USA consistently lagged, recording the lowest life expectancy every year since 2001, and the UK frequently occupied the second lowest position in the most recent decade. The disparities in life expectancy at birth between the best and worst-performing countries have widened over time, with the gaps doubling for men and increasing by 30% for women between Australia and the USA from 1990 to 2019.

The research highlighted that Australians benefit from lower death rates across nearly all age groups, particularly between ages 45 and 84. Critical health issues contributing to life expectancy differences in this age range include ischaemic heart disease, other circulatory diseases, cancers, respiratory diseases, and neurological conditions, predominantly Alzheimer’s disease and related dementias. Additionally, Australia shows lower mortality from external causes like drugs, alcohol, and certain cancers.

Regarding regional differences within countries, the study found the lowest life expectancy in certain US states. In contrast, all regions in the UK and Ireland surpassed life expectancy thresholds of 81 years for women and 76.5 years for men. Australia exhibited the least within-country inequality in life expectancy, particularly noticeable after age 40, with Canada following. In contrast, inequality among both sexes was most pronounced in New Zealand, Ireland, and the USA.

While acknowledging limitations such as potential inconsistencies in the cause-of-death coding at older ages, the researchers suggest several factors for Australia’s superior performance, including a high proportion of overseas-born residents and robust public health policies on issues like smoking, gun ownership, and mental health. Despite its leading position, Australia faces challenges in reducing health disparities, especially among its indigenous populations and in combating obesity.

The study concludes by positing that Australia could serve as a model for other English-speaking countries, particularly those performing less well like the USA and UK, to improve both lifespans and reduce inequalities in life expectancy.

More information: Rachel Z Wilkie et al, Life expectancy and geographic variation in mortality: an observational comparison study of six high-income Anglophone countries, BMJ Open. DOI: 10.1136/bmjopen-2023-079365

Journal information: BMJ Open Provided by BMJ Group

Recent Studies Show Promise for Enhancing the Efficacy of Widely Used Diabetes and Weight-Loss Medications

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Recent findings from the University of Michigan suggest that a network of proteins within the central nervous system could enhance the efficacy and mitigate side effects of common diabetes and weight-loss medications. They were published today in the Journal of Clinical Investigation; the research centres on two proteins, melanocortin three and melanocortin 4, located predominantly on the surface of brain neurons. These proteins are crucial in regulating feeding behaviours and maintaining energy balance in the body.

Roger Cone, a U-M physiologist who spearheaded the research, explained that melanocortin three and melanocortin 4 influence a range of functions, from monitoring long-term energy reserves to interpreting signals from the gut about short-term fullness or satiety. The study mainly looks at GLP-1 agonists—such as semaglutides and tirzepatides—renowned for their effectiveness against not only type 2 diabetes but also obesity, heart disease, and potentially addiction. These drugs operate by emulating a natural hormone produced by the gut when complete, which then prompts the brain to curb feeding behaviour.

Cone posed a critical question: “How do GLP-1 drugs, which modulate satiety signals, perform when we prime the melanocortin system?” To explore this, his team conducted experiments using mouse models, comparing the effects of various hormones that decrease food intake. They tested these hormones in typical mice, in those lacking the MC3R protein genetically, in mice treated with chemicals that inhibit MC3R, and in those administered a drug that enhances MC4R activity. Since MC3R naturally curtails MC4R activity, blocking MC3R while boosting MC4R has comparable outcomes.

The study, led by first author Naima Dahir, a postdoctoral research fellow in Cone’s lab, discovered that either inhibiting MC3R or boosting MC4R activity heightened the mice’s sensitivity to GLP-1 drugs and other hormones impacting feeding behaviour. Mice treated with a combination of a GLP-1 drug and either an MC4R agonist or an MC3R antagonist experienced up to a fivefold increase in weight loss and reduced feeding compared to those treated solely with GLP-1 drugs.

“Our findings reveal that activating the central melanocortin system significantly increases the response to not just GLP-1s, but to all anti-feeding hormones we tested,” noted Cone. The research team also monitored brain activity associated with nausea—a common side effect of GLP-1 drugs—and found no increase in such activity when GLP-1 drugs were used alongside modifications to the melanocortin system. In contrast, we stimulated melanocortin neurons, which markedly enhanced the GLP-1 drug-induced activation of neurons in brain areas responsible for feeding.

These results suggest that combining existing GLP-1 drugs with an MC4R agonist could amplify the drugs’ desired effects fivefold without exacerbating unwanted side effects. This approach could allow patients who are particularly sensitive to side effects to use lower doses or enhance outcomes for patients who are unresponsive to current drug dosages. However, further drug development and clinical trials are necessary before such treatments can be implemented.

Although the research was conducted in mouse models, Cone remains optimistic about its applicability to humans. “The melanocortin system is highly conserved in humans,” he remarked. “Based on our decades of research into these proteins, which has shown consistent results between mice and humans, I believe these findings will likely be transferable to clinical settings.”

More information: Naima S. Dahir et al, Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice, Journal of Clinical Investigation. DOI: 10.1172/JCI178250

Journal information: Journal of Clinical Investigation Provided by University of Michigan

Ageing and Dementia-Related Memory Decline: The Predictive Role of Dendritic Spine Head Diameter in Elderly Memory Retention

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Memory declines with age, often marked by a diminished ability to recall personal experiences. Traditionally associated with the degeneration of dendritic spines—critical elements of synaptic connections in the brain—this process has been reevaluated in light of new research. A study published in Science Advances, conducted by teams from the University of Alabama at Birmingham and Rush University Medical Center in Chicago, proposes that retaining memories from past experiences depends more on the quality rather than the quantity of synaptic connections in older people.

Jeremy Herskowitz, Ph.D., associate professor in the Department of Neurology at UAB and corresponding author of the study, characterizes the findings as a significant departure from established beliefs. For decades, the dominant theory posited that memory decline was primarily due to the loss of dendritic spines, indicating synaptic deterioration. This study reveals that, although synapses diminish with age—a process considered normal from ages 40 to 85—the remaining synapses can compensate for this loss, challenging the previous understanding of memory decline’s mechanics.

The implications of this discovery are particularly promising for the elderly population. Herskowitz explains that the study demonstrates an enduring synaptic plasticity in older individuals, which can still effectively support memory retention. This insight suggests that therapies aimed at remodelling dendritic spines and synapses could significantly enhance memory preservation and cognitive function in ageing individuals or those suffering from memory impairments associated with Alzheimer’s disease.

The Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) at Rush University provided the foundation for this research. This project enrols Catholic nuns, priests, and brothers over the age of 65 who are free from known dementia at enrollment and agree to donate their brains for research post-mortem. The study examined brain samples from 128 ROSMAP participants, with an average age of 90.5 years at death, who had undergone annual cognitive testing covering multiple domains.

In their analysis, Herskowitz and his team stained and photographed thin slices of brain tissue, constructing three-dimensional digital reconstructions of 55,521 dendritic spines across 2,157 neurons. They utilized innovative statistical and machine learning techniques to assess correlations between various spine morphology measurements and multiple indicators of brain function, age, and Alzheimer’s disease pathology. Their findings highlighted that larger dendritic spine head diameters in the temporal cortex were associated with better episodic memory performance, underscoring the importance of synaptic strength over quantity in memory preservation in old age.

This research, which spanned over two and a half years and continued through the COVID-19 pandemic under strict conditions, opens new pathways for therapeutic interventions focusing on enhancing synaptic strength and spine head diameter. These approaches could potentially offer more significant benefits for older adults, particularly those in the preclinical phases of Alzheimer’s disease, emphasizing the fundamental role of synapses in brain function and the dynamic process of synaptic formation and elimination as part of brain plasticity.

More information: Courtney K. Walker et al, Dendritic spine head diameter predicts episodic memory performance in older adults, Science Advances. DOI: 10.1126/sciadv.adn5181

Journal information: Science Advances Provided by University of Alabama at Birmingham