Monthly Archives: November 2024

Cognitive Decline Associated with Heart Failure, Atrial Fibrillation, and Coronary Artery Disease

The recent scientific statement from the American Heart Association, published in their journal Stroke, highlights a crucial link between cardiovascular diseases and cognitive health. The paper “Cardiac Contributions to Brain Health,” delves deep into the intricate relationships among heart failure, atrial fibrillation, coronary heart disease, and cognitive impairment, including the increased risk of dementia.

This detailed review collates the latest research that explores the connections between cardiovascular well-being and brain health, specifically focusing on cognitive impairments or neuropsychological dysfunctions. The statement draws significant attention to the interconnected nature of heart and brain health, underscoring its importance for overall well-being. It also emphasizes that both stroke and cognitive decline are substantial determinants of brain health, which are chronic and disabling conditions that profoundly impact individuals and society at large. Fernando D. Testai, M.D., Ph.D., FAHA, the chair of the statement writing group and a prominent figure in neurology and rehabilitation at the University of Illinois, advocates for managing heart health from an early age. This proactive approach is essential to prevent cardiovascular diseases, protect brain health, and reduce the likelihood of cognitive decline later in life.

Dr. Testai further elaborates that dementia, often perceived as an incurable and relentless condition, might be influenced by early interventions focused on a healthy lifestyle and the treatment of vascular risk factors. Such measures could preserve normal brain function and mitigate the impact of Alzheimer’s disease and other dementias.

Specifically, heart failure, a significant public health concern linked with high blood pressure, obesity, and Type 2 diabetes, has been shown to significantly affect cognitive functions required for tasks like self-care and medication management, particularly in older adults. Studies indicate that nearly half of the individuals suffering from heart failure experience cognitive impairments that can affect language, memory, and executive functions. Heart failure may cause brain injuries through mechanisms like reduced blood flow leading to mini-strokes or silent brain injuries, chronic inflammation, and neurohormonal activation.

Similarly, atrial fibrillation, the most prevalent heart rhythm disorder among adults, has been found to increase the risk of cognitive impairment by 39%, according to a large meta-analysis. The condition, which is closely linked to stroke, also shares multiple risk factors with dementia, such as high blood pressure and Type 2 diabetes. These risk factors can induce structural and functional brain changes that lead to cognitive decline. Current treatments for atrial fibrillation, such as anti-clotting medications and rhythm control procedures like catheter ablation, may potentially reduce the risk of cognitive dysfunction.

Coronary heart disease, another focus of the statement, is also significantly associated with an increased risk of dementia and cognitive impairment. Research involving more than one million adults shows that those with heart disease are 27% more likely to develop dementia than those without. Heart attacks, in particular, are linked to a sharp decline in cognitive functions, such as memory and executive functions. Coronary heart disease impacts brain function through mechanisms like inflammation that affects the blood-brain barrier and reduced blood flow to the brain, which can lead to cognitive impairments.

The study underscores the necessity of a holistic approach to patient care that integrates heart health management throughout an individual’s life. Emphasizing prevention over cure, Dr. Testai calls for more research to solidify the understanding of how cardiovascular care can enhance brain health and how various factors such as gender, race, and ethnicity may influence the relationship between cardiovascular and brain health. The push towards early intervention and promoting heart health through resources encouraging healthy lifestyles is crucial to reducing the risk of cognitive impairment and improving overall quality of life.

More information: Fernando D. Testai et al, Cardiac Contributions to Brain Health: A Scientific Statement From the American Heart Association, Stroke. DOI: 10.1161/STR.0000000000000476

Journal information: Stroke Provided by American Heart Association

Research Indicates Sweet Tooth May Elevate Risks of Depression, Diabetes, and Stroke

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New research from the University of Surrey has established a link between a predilection for sugary foods and an increased risk of depression, diabetes, and stroke. Published in the Journal of Translational Medicine, this comprehensive study utilised anonymised dietary preferences from 180,000 participants sourced from the UK Biobank. By employing artificial intelligence, researchers were able to classify these individuals into three distinct dietary profiles:

The ‘Health-Conscious’ profile includes individuals favouring fruits and vegetables over animal products and sugary treats. The ‘Omnivore’ profile describes those with a diverse palate, including meats, fish, some vegetables, sweets, and desserts. Lastly, the ‘Sweet Tooth’ profile is characterised by a preference for sugary foods and beverages, with less interest in healthier alternatives like fruits and vegetables.

The Surrey research team further analysed the UK Biobank data, focusing on blood samples tested for 2,923 proteins and 168 metabolites. Proteins play a crucial role in the body, aiding in everything from infection defence to muscle function and cognitive processes. Metabolites, however, are small molecules that arise during digestion and other metabolic processes, providing insights into the body’s functional state. The researchers could discern significant biological differences by examining the variations in these proteins and metabolites across the groups.

Professor Nophar Geifman, the study’s senior author and a Professor of Health and Biomedical Informatics at the University of Surrey, commented on the findings, stating that one’s dietary preferences could be directly connected to one’s health outcomes. He highlighted that those with a strong inclination towards sugary foods — identified as the ‘Sweet Tooth’ group — were found to be 31% more likely to suffer from depression. This group also displayed elevated rates of diabetes and vascular heart issues in comparison to their counterparts.

Professor Geifman emphasised the significance of employing data-driven AI techniques to identify and categorise individuals based on their dietary habits, noting that these categories correlate meaningfully with health outcomes and biological markers. He pointed out the detrimental role processed sugars often play in modern diets, advocating for a societal shift towards more mindful eating habits while clarifying that the intent is not to dictate dietary choices but to provide information.

The study also examined the three groups via standard blood biochemistry tests. It was found that the ‘Sweet Tooth’ group had increased levels of C-reactive protein, a marker for inflammation, higher glucose levels and poor lipid profiles, indicative of heightened risks for diabetes and cardiovascular diseases. Conversely, the ‘Health-Conscious’ group reported higher dietary fibre intake and reduced risks for heart failure, chronic kidney diseases, and stroke. The ‘Omnivore’ group presented with moderate health risks.

These findings are further contextualised by data from the British Nutrition Foundation, which indicates that between 9% and 12.5% of caloric intake in the UK derives from free sugars —sugars added to foods or beverages. Notably, biscuits, buns, cakes, pastries, and fruit pies are significant sources of free sugars for adults. At the same time, sugary soft drinks and alcoholic beverages also contribute significantly to the overall intake of free sugars.

More information: Hana F. Navratilova et al, Artificial intelligence driven definition of food preference endotypes in UK Biobank volunteers is associated with distinctive health outcomes and blood based metabolomic and proteomic profiles, Journal of Translational Medicine. DOI: 10.1186/s12967-024-05663-0

Journal information: Journal of Translational Medicine Provided by University of Surrey

Chronic Pain from Alcohol Withdrawal May Be Permanent for Heavy Drinkers

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Increased sensitivity to typically non-painful stimuli, known as “allodynia,” ranks among the principal physical manifestations of alcohol withdrawal. Allodynia reflects a heightened response to mechanical stimuli, signalling chronic pain. A recent study conducted by scientists at Scripps Research and published in Pharmacological Research on October 11, 2024, delves into how the severity and persistence of this sensitivity correlate directly with the quantity of alcohol consumed over time. According to their findings, in animal models where alcohol consumption was moderate, the hypersensitivity to pain reverted to normal levels within approximately a week of cessation. However, in models simulating heavy alcohol intake, this sensitivity extended beyond the cessation period, indicating a potentially permanent change.

The research highlights that the protracted pain associated with withdrawal in heavy drinkers is linked to alterations in endocannabinoids, which are vital chemical messengers in the nervous system. The study pinpoints a specific endocannabinoid that could be a promising target for developing treatments aimed at mitigating allodynia in individuals suffering from alcohol use disorder (AUD).

Marisa Roberto, PhD, the study’s senior author and a professor in the Department of Neuroscience at Scripps Research, articulates that while temporary changes in mechanical sensitivity induced by long-term alcohol intake can be reversed in cases of moderate drinking by halting consumption, the alterations observed in heavy drinkers are likely irreversible without pharmacological intervention. The study proposes that modulating the metabolism of the endocannabinoid 2-AG could offer a new avenue for treating neuropathic pain, which is frequently exacerbated by chronic and excessive alcohol consumption.

AUD affects nearly 29 million individuals in the U.S. and significantly increased during the COVID-19 pandemic. It is particularly associated with neuropathic pain that often intensifies during withdrawal phases. This type of pain is more prevalent among women, both under the influence of alcohol and during withdrawal phases. Yet, the underlying mechanisms driving the increase in sensitivity due to alcohol and its withdrawal remain largely unexplored.

The researchers utilised two rat models to study the effects of alcohol consumption and subsequent withdrawal on allodynia. One model simulated a higher preference for alcohol, indicative of heavy drinking, while the other represented moderate drinking levels. After 5 weeks of alcohol consumption followed by 26 days of abstinence, it was observed that, before alcohol exposure, rats in the heavy-drinking model exhibited a baseline increased sensitivity, which did not further escalate with alcohol consumption. In contrast, the moderate-drinking rats showed a spike in sensitivity levels during alcohol intake. However, upon withdrawal, allodynia was evident in both groups, albeit the moderate drinkers saw a return to normal sensitivity levels after several days, with a noted delay in female rats.

Significantly, the time frame of observed allodynia in the heavy-drinking rats did not show signs of subsidence even after an extended period of abstinence, which, when extrapolated to human timelines, equates to about 30 months. This suggests a potentially permanent condition necessitating urgent pharmacological treatment, as indicated by Vittoria Borgonetti, PhD, co-first author of the study. Nonetheless, she advises that further testing is required to validate these findings in human contexts.

Further investigations into the dorsal root ganglia of the rats revealed that alcohol withdrawal led to diminished levels of 2-AG in the heavy-drinking models, with these reduced levels correlating directly with the observed allodynia. This discovery earmarks 2-AG metabolism as a potential therapeutic target. Additionally, altered levels of eicosanoids, immune signalling molecules, were noted in the female rats, underscoring significant sex differences in the impacts of AUD and chronic pain, a gap in knowledge that the research team intends to address in future studies.

Looking ahead, the team plans to explore whether restoring physiological levels of 2-AG at the onset of withdrawal through pharmacological modulators could prevent or alleviate mechanical allodynia triggered by alcohol consumption. They also aim to assess how treatments might affect males and females differently, tailoring therapeutic approaches to individual needs.

More information: Vittoria Borgonetti et al, Excessive alcohol intake produces persistent mechanical allodynia and dysregulates the endocannabinoid system in the lumbar dorsal root ganglia of genetically-selected Marchigian Sardinian alcohol-preferring rats, Pharmacological Research. DOI: 10.1016/j.phrs.2024.107462

Journal information: Pharmacological Research Provided by Scripps Research Institute

Hoarding Disorder: Promising Results from ‘Sensory CBT’ Treatment Approach

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Imagery rescripting, a technique commonly used in cognitive behavioural therapy (CBT), is showing promising results as a potential treatment strategy for individuals with hoarding disorder, according to a recent study conducted by psychology researchers at the University of New South Wales (UNSW). This technique involves rehearsing alternative outcomes of discarding items through the power of imagination, suggesting a new avenue for addressing the complex challenges those hoarders face.

Hoarding disorder is a condition that significantly impairs individuals’ ability to function and tends to worsen with age. Those affected by this disorder often develop deep emotional attachments to their possessions, leading to excessive accumulation of items and severe difficulty in discarding anything, regardless of its actual value. This behavioural pattern can result in considerable clutter encroaching upon the livable space within their homes, often preventing normal home activities and posing serious health and safety risks. The disorder can isolate individuals, exacerbate stress, and deter them from seeking treatment due to stigma and a lack of effective interventions.

The research team, led by Mr Isaac Sabel from the Grisham Research Lab at UNSW, an experimental clinical psychology group, has explored the benefits of imagery rescripting in treating hoarding disorder. This method engages individuals in altering the anticipated adverse outcomes associated with discarding items by substituting them with positive or neutral alternatives. By doing so, it addresses the intrusive and distressing mental images that frequently occur in those with hoarding disorder, which can hinder their ability to part with items.

The study encompassed 176 participants who exhibited strong hoarding tendencies. They participated in an online intervention that involved selecting an item they had struggled to discard. Participants were asked to write down their feared outcomes if they were to discard the item and then engage in an exercise to rescript these outcomes based on one of four different therapeutic approaches: imagery rescripting, cognitive restructuring, imaginal exposure, and a control condition focusing on positive imagery. Following these interventions, the participants were encouraged to attempt to discard the item.

The findings revealed that those who engaged in imagery rescripting reported increased happiness, motivation, and a greater likelihood of discarding the item than those who underwent other interventions. This technique also proved more effective in reducing negative emotions such as anxiety, sadness, and anger while enhancing feelings of relaxation and happiness around the act of discarding. Furthermore, the study indicated that the effectiveness of imagery rescripting might be influenced by an individual’s ability to visualise vividly; participants who could more clearly imagine various scenarios tended to find discarding less challenging.

These promising results have been further validated in a second study led by UNSW researchers. This study compared imagery rescripting with thought listing, another previously found effective in facilitating the discarding process. Preliminary findings suggest that imagery rescripting not only outperformed thought listing in improving motivation and positivity around discarding but also showed potential for broader application in treating hoarding disorder.

Hoarding disorder affects approximately 2.5% of the working-age population in Australia, equating to around 715,000 individuals. The condition is often linked to significant psychological distress and social impairments comparable to those experienced by individuals living with schizophrenia. It can lead to unsanitary living conditions, increased risk of accidents, and substantial social and financial costs to restore homes to a safe, liveable state.

The study conducted by UNSW highlights the potential of imagery rescripting not only as a treatment for reducing the distress associated with discarding but also as a means of addressing the deeper psychological issues that fuel hoarding behaviour. By focusing on sensory-rich details to create immersive and emotionally evocative experiences, this technique offers a novel therapeutic avenue that could be particularly beneficial in early interventions and for individuals in remote areas where access to traditional therapy is limited.

More information: Isaac Sabel et al, Imagining Letting Go: a Preliminary Test of Written Imagery Rescripting to Facilitate Discarding in a High Hoarding Sample, Journal of Psychopathology and Behavioral Assessment. DOI: 10.1007/s10862-024-10171-y

Journal information: Journal of Psychopathology and Behavioral Assessment Provided by University of New South Wales

A Study on the Positive Impact of Fermented Black Garlic Extract in Treating Prostate Cancer

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Researchers at the University of Cordoba and the Maimónides Biomedical Research Institute (IMIBIC) are exploring the potential benefits of fermented black garlic extract as a protective agent against inflammation and prostate cancer progression. This investigation utilises human prostate cancer cell models in a laboratory setting.

In Spain, prostate cancer ranks as the third most common cause of cancer-related deaths among men. The disease can evolve from benign prostatic hyperplasia to localised prostate cancer and eventually to metastatic castration-resistant cancer—a stage for which treatment options are severely limited.

The OncObesity and Metabolism group, comprised of researchers from the University of Córdoba and IMIBIC, conducted the study. This team focuses on the antitumour properties of natural compounds that could be integrated into diets to combat various cancer types.

Recent research undertaken by Raúl M. Luque, María Loreta Libero, and Antonio J. Montero centred on the effects of fermented black garlic extract on prostate cancer cells. Building on previous findings from mouse experiments, which highlighted the extract’s anti-inflammatory properties and acknowledged the significant role of inflammation in prostate cancer development, the team assessed its impacts on cellular disease models.

Antonio Montero reported that the team tested the extract on different prostate cancer cell models, discovering its ability to diminish several indicators of tumour aggressiveness, such as cell proliferation while sparing normal prostate cells. This finding suggests that the compound could be a dietary supplement without adverse effects on healthy cells.

The team’s principal investigator, Raúl Luque, elaborated on the anticancer capabilities of the compound. He noted that following the demonstration of these effects, the research aimed to identify which molecular pathways were influenced by the compound. It was found that the extract altered key cancer-related signalling pathways, particularly those associated with inflammation. Montero explained that the treatment lessened the inflammatory milieu typically observed in this form of cancer, with increased efficacy in pro-inflammatory conditions. This reduction in local inflammation might contribute to the decreased aggressiveness of the cancer observed following treatment with the extract.

Luque suggested that the findings indicate the compound’s potential as an effective option to mitigate some of the complications faced by patients advancing towards more severe and aggressive stages of prostate cancer.

The next phase of research would involve a pilot study with individuals who have a familial history of prostate cancer or a clinical trial with existing patients to assess further whether the progression of the disease can be slowed or halted by this compound.

More information: Maria Loreta Libero et al, The Protective Effects of an Aged Black Garlic Water Extract on the Prostate, Nutrients. DOI: 10.3390/nu16173025

Journal information: Nutrients Provided by University of Córdoba

Intestinal Hormones May Be Crucial in Combating Fatty Liver Disease

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The global rise in fatty liver disease, primarily fuelled by high-fat diets and obesity, presents a significant and growing health challenge. Characterised by the excessive storage of fats in the liver, this condition increases the risk of various metabolic disorders and underscores the complex interplay between diet and liver health. Although traditional research has predominantly focused on understanding fat metabolism directly within the liver, recent studies have begun to highlight the pivotal influence of the gut in this multifaceted process. Among the key players in this interaction are proglucagon-derived peptides (PGDPs) such as glucagon, GLP-1, and GLP-2. These hormones, all derived from the proglucagon molecule, have been shown in previous studies to influence lipid accumulation in the liver indirectly. However, how they contribute to liver fat accumulation remains largely unclear.

In a groundbreaking study led by Associate Professor Yusuke Seino of Fujita Health University, published on 14 July 2024 in the journal Nutrients, new light has been shed on the role of PGDPs in regulating fat absorption and subsequent liver fat buildup. The research team, including Mr Koki Nishida, Mr Atsushi Suzuki, and Mr Yoshiki Hirooka from Fujita Health University, as well as Mr Yoshikata Hayashi from Nagoya University, employed genetically modified mice lacking PGDPs (GCGKO mice) to explore their response to a high-fat diet over seven days, aiming to uncover new preventative strategies for fatty liver.

The findings were revealing. “When both GCGKO mice and control mice were subjected to a high-fat diet for one week, the GCGKO mice demonstrated a significantly lower increase in hepatic free fatty acid and triglyceride levels, as well as reduced adipose tissue weight,” explained Dr Seino. This reduction in lipid accumulation was linked to decreased lipid absorption through the CD36 pathway in the intestinal tract despite the mice’s reduced liver fat-burning (β-oxidation) capacity.

Furthermore, the research identified a decrease in the expression levels of genes associated with free fatty acid oxidation in the high-fat diet-fed GCGKO mice. Notably, the duodenum’s mRNA levels of Pparα (peroxisome proliferator receptor alpha) and Cd36 (cluster of differentiation 36) were lowered, correlating with diminished fat uptake in the intestines and increased faecal cholesterol content. This indicates that the absence of PGDPs prevents diet-induced fatty liver primarily by reducing intestinal fat absorption.

Interestingly, the study also pointed to lower plasma triglyceride levels during the oral fat tolerance test in HFD-fed GCGKO mice, further substantiating the reduced lipid absorption. Moreover, the research underscored a complex relationship between diet, hormonal responses, and intestinal microbiota. Notable shifts in gut bacteria were observed in HFD-fed GCGKO mice, with increases in Parabacteroides and decreases in Lactobacillus, which are associated with resistance to obesity. These microbial changes highlight the potential of dietary and hormonal interventions to enhance gut health and metabolic functions.

Expanding on the implications of their findings, Dr Seino suggested, “A more detailed examination of how PGDPs specifically regulate lipid absorption in the gut could clarify the relationship between diet, hormones, and intestinal bacteria to a degree that allows us to recommend a diet that is less conducive to obesity and fatty liver disease.” Looking to the future, he added, “Oral dual antagonists of GLP-2 and glucagon could potentially become effective therapies for obesity and fatty liver, particularly due to their roles in insulin sensitivity and lipid metabolism.”

In conclusion, these findings open the door to the development of targeted therapies designed to tackle this prevalent health issue, potentially improving the health outcomes for millions of individuals globally affected by fatty liver disease. This study enhances our understanding of the biochemical pathways involved and sets the stage for innovative treatments that could revolutionise the management of fatty liver disease.

More information: Koki Nishida et al, Impaired Fat Absorption from Intestinal Tract in High-Fat Diet Fed Male Mice Deficient in Proglucagon-Derived Peptides, Nutrients. DOI: 10.3390/nu16142270

Journal information: Nutrients Provided by Fujita Health University