Obstructive sleep apnea may directly cause early cognitive decline

by Frontiers

Credit: Unsplash/CC0 Public Domain

Obstructive sleep apnea (OSA) is a potentially dangerous condition. During sleep, the throat muscles of people with OSA relax and block the airflow into the lungs, so that they repeatedly stop breathing. Common symptoms of OSA include restless sleep, loud snoring, daytime sleepiness, and prolonged headaches in the morning—highly debilitating for patients and their partners.

09 april 2023--OSA is currently underdiagnosed: it may occur in as much as 15 to 30% of men and 10 to 15% of women, or approximately 1 billion adults worldwide, of whom an estimated 80% don't know they have it. Major risk factors for OSA include middle or old age, being obese, smoking, chronic nasal blockage, high blood pressure, and being male.

Now, researchers from the UK, Germany, and Australia have shown for the first time that in middle-aged men, OSA can also cause early cognitive decline, even in patients who are otherwise healthy and not obese. The results are published in Frontiers in Sleep.

"We show poorer executive functioning and visuospatial memory and deficits in vigilance, sustained attention, and psychomotor and impulse control in men with OSA. Most of these deficits had previously been ascribed to co-morbidities," said Dr. Ivana Rosenzweig, a neuropsychiatrist who heads the Sleep and Brain Plasticity Centre at King's College London, and the lead author of the study.

"We also demonstrated for the first time that OSA can cause significant deficits in social cognition."

Rare cohort without co-morbidities

Rosenzweig and colleagues studied a group of 27 men between the ages of 35 and 70 with a new diagnosis of mild to severe OSA but without any co-morbidities. Such patients are relatively rare, because most men and women with OSA have co-morbidities such as cardiovascular and metabolic disease, stroke, diabetes, chronic systemic inflammation, or depression.

The men were not currently smokers or alcohol abusers, and were not obese (i.e., with a body mass index (BMI) below 30). As a control, the researchers studied a group of seven age-, BMI-, and education-matched men without OSA. The OSA diagnosis was confirmed by a so-called WatchPAT test of their respiratory function during sleep at home, and also by video-polysomnography at King's College sleep center.

With the latter method, the brain waves of sleeping subjects were measured by electroencephalography (EEG), while their blood oxygen levels, heart rate, breathing, and eye and leg movements were tracked.

The scientists also tested the subjects' cognitive function with the CANTAB or 'Cambridge Neuropsychological Test Automated Battery' of tests.

Premature cognitive decline

The results showed that patients with severe OSA had poorer vigilance, executive functioning, short-term visual recognition memory, and social and emotion recognition than the matched controls. Patients with mild OSA performed better in these domains than patients with severe OSA, but worse than the controls.

"The most significant deficits…were demonstrated in the tests that assess both simultaneous visual matching ability and short-term visual recognition memory for non-verbalizable patterns, tests of executive functioning and cued attentional set shifting, in vigilance and psychomotor functioning, and lastly, in social cognition and emotion recognition," wrote the authors.

The authors conclude that OSA is sufficient to cause these cognitive deficits, which previous studies had attributed to the most common co-morbidities of OSA such as systemic hypertension, cardiovascular and metabolic diseases, and type 2 diabetes.

Unclear mechanism

But what is the mechanism by which OSA causes premature cognitive decline? The authors speculated that the cognitive deficits are due to intermittent low oxygen and high carbon dioxide in the blood, changes in blood flow to the brain, sleep fragmentation, and neuroinflammation in OSA patients.

"This complex interplay is still poorly understood, but it's likely that these lead to widespread neuroanatomical and structural changes in the brain and associated functional cognitive and emotional deficits," said Rosenzweig.

Whether co-morbidities have similar negative effects on cognition above and beyond those caused directly by OSA is not yet clear.

"Our study is a proof of concept. However, our findings suggest that co-morbidities likely worsen and perpetuate any cognitive deficits caused directly by OSA itself," said Rosenzweig.

"What remains to be clarified in future studies is whether co-morbidities have an additive or synergistic effect on the latter deficits, and whether there is a difference in brain circuitry in OSA patients with or without co-morbidities."

More information: Ivana Rosenzweig et al, Distinct cognitive changes in male patients with obstructive sleep apnea without co-morbidities, Frontiers in Sleep (2023). DOI: 10.3389/frsle.2023.1097946 , www.frontiersin.org/articles/1 … le.2023.1097946/full

Provided by Frontiers 

 

Modified Mediterranean ketogenic diet may benefit adults at risk for Alzheimer's disease

by Atrium Health Wake Forest Baptist

Credit: Unsplash/CC0 Public Domain

Following a Mediterranean-based ketogenic diet may decrease the risk of Alzheimer's disease, according to a new study from scientists at Wake Forest University School of Medicine.

09 april 2023--In the study, researchers compared a low-fat diet with a diet consisting of healthy fats/protein and low carbohydrates—the modified Mediterranean ketogenetic diet—and found that the modified diet showed robust changes in a biological pathway that is linked to Alzheimer's disease.

The findings were published online today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

According to the Alzheimer's Association, more than 6.5 million Americans are living with Alzheimer's disease, and 1 in 3 seniors die with the disease or another form of dementia.

"We hope that better understanding this complex relationship between diet, cognitive status and gut health will lead to new interventions to prevent and treat Alzheimer's disease," said Suzanne Craft, Ph.D., professor of gerontology and geriatric medicine at Wake Forest University School of Medicine.

This study builds upon previous research from Craft's team showing that a modified ketogenic diet may prove beneficial in the prevention of cognitive decline.

The randomized, single-site study involved 20 adults, nine diagnosed with mild cognitive impairment (MCI) and 11 with normal cognition. These participants were randomly assigned to follow either the low-carbohydrate modified Mediterranean-ketogenic diet or a low-fat, higher carbohydrate diet for six weeks then, after a six-week "washout" period, to switch to the other diet.

Stool samples were collected from participants at the beginning and end of each diet period, and six weeks after the washout of the second diet to analyze changes in gut microbiome—the good and bad bacteria that live in the gastrointestinal tract.

Researchers found that participants with MCI on the modified Mediterranean ketogenic diet had lower levels of gamma-aminobutyric acid (GABA) and of GABA-producing microbes. Participants on this diet also had higher levels of GABA-regulating bacteria. GABA is the primary inhibitory neurotransmitter in the central nervous system, and GABA dysfunction is associated with neuropsychiatric conditions including Alzheimer's disease.

"Our study is the first to show that diet modulates GABA differently in MCI," Craft said.

The study also showed that participants with MCI who had curcumin in their diets also had lower levels of BSH-containing bacteria. These bacteria regulate bile acids produced by the liver and gut. Lower levels suggest reduced gut motility, a phenomenon in which food and waste take longer to transit the gut. Abnormal bile acid profiles have been observed in adults with Alzheimer's disease.

"These findings provide crucial insight into how diet may affect the microbiome and improve brain health," Craft said. "Larger studies are needed to assess the role diet interventions play in patients with cognitive impairment."

More information: Amanda Hazel Dilmore et al, Effects of a ketogenic and low‐fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease, Alzheimer's & Dementia (2023). DOI: 10.1002/alz.13007

Provided by Atrium Health Wake Forest Baptist

 

Lifespans into the 140s predicted by centuries-old Gompertz law

by Justin Jackson , Medical Xpress

Dividing changes in mortality rates between compression and postponement. Credit: PLOS ONE (2023). DOI: 10.1371/journal.pone.0281752

A recent paper in the journal PLOS ONE suggests that humans have yet to reach their maximum age and that there might not even be one. In the paper, "Mortality postponement and compression at older ages in human cohorts," David Mcarthy of the Terry College of Business, University of Georgia, and his former Ph.D. student, Po-Lin Wang, currently at Muma College of Business, University of Southern Florida, use mathematical modeling of longevity trends, without reference to any biological, social or medical science to extrapolate the future of human longevity.

09 april 2023--Typically in the introductory section of an academic study, the author provides context on the paper's topic, including relevant citations to help understand what body of work the study is building on.

The first citation in the introduction is a psalm from the King James Bible, which the authors suggest indicates that ancient Hebrews, around 2,500 years ago, believed the maximum age a human could reach was 80 years old. Next, there is a citation of a poem by Horace, from which the authors suggest that the ancient Romans estimated the maximum lifespan of humans to be 100 or 110 years old.

There is the uncited reference to the current human longevity record being 122, unchanged since 1997, which is likely referring to Jeanne Calment, a wealthy French woman who holds the record for the world's most extended verified lifespan. While it is an astonishing age to reach, it has been long predicted to be feasible that someone should reach this age as an outlier. What accompanies that prediction is an expectation that there would not be anyone else close to them in age, and in fact, the next closest oldest verified lifespan is a full three years less. Currently (and I do mean currently), there are eight people over the age of 114 on the planet, all women, with the oldest being 116.

It should also be noted that the lead author of the study, David McCarthy, is an editorial board member and frequent contributor to the Journal of Pension Economics and Finance and describes himself as a policy expert. Mathematical models are commonly used for setting pension goals and life insurance premiums, and predicting the ages that people will live has a long history in the world of finance. For most of that history, a preferred mathematical law from the 19th century has been relied upon with reasonable accuracy.

Gompertz law

The Gompertz law used in the study is a 202-year-old mathematical formula to model mortality rates. The law states that mortality rates increase exponentially with age, meaning the risk of death increases by a magnitude approximately every decade after age 50. The Gompertz law is named after Benjamin Gompertz, a British mathematician who first proposed the law in 1825.

Gompertz himself only believed that his model was reliable up to the age of 85; Gompertz died at age 86. Still, at 86, Gompertz was nine years older than the life expectancy of a male born in the U.S. today.

The paper in PLOS ONE refrains from involving biology in predicting a maximum age. However, it does conclude with math alone that birth year cohorts of individuals born after 1950 should be the first to experience a significant postponement in the historical progression of mortality. By calculating a fixed mortality risk rate for each year after, the study forecasts a future where longevity records will be commonly broken after 2073, with some prediction graphs running into the 140s.

While a combination of medical advances and increased starting populations by birth year favor the extension of the maximum age, the ability to reach these more extreme lifespans will require much more than statistical chance. It will require a much deeper understanding of cellular function, DNA repair, cancer mitigation and tissue rejuvenation. It will likely require lab-assisted prefertilization genetic modifications to equip the body with a genome that can withstand 140 years of cellular replication without disruptive mutations or senescence—and that generation, along with the required knowledge, has not yet been born.

More information: David McCarthy et al, Mortality postponement and compression at older ages in human cohorts, PLOS ONE (2023). DOI: 10.1371/journal.pone.0281752

Journal information: PLoS ONE 

 

New study shows SARS-CoV-2 infection accelerates the progression of dementia

by IOS Press

The possible common pathomechanisms linking multiple sclerosis and post-COVID-19 brain involvement (A). Proposal of a new codename regarding post-COVID-19 cognitive sequelae (B). Credit: Journal of Alzheimer's Disease Reports (2023). DOI: 10.3233/ADR-220090

Infection with SARS-CoV-2 has a significant impact on cognitive function in patients with preexisting dementia, according to new research published in the Journal of Alzheimer's Disease Reports. Patients with all subtypes of dementia included in the study experienced rapidly progressive dementia following infection with SARS-CoV-2.

09 april 2023--Since the first wave of COVID-19, neurologists have noticed both acute and long-term neurological syndromes and neuropsychiatric sequelae of this infectious disease. Insights into the impact of COVID-19 on human cognition has so far remained unclear, with neurologists referring to "brain fog."

A group of researchers driven to gain a better understanding of and dissipate this fog investigated the effects of COVID-19 on cognitive impairment in 14 patients with preexisting dementia (four with Alzheimer's disease [AD], five with vascular dementia, three with Parkinson's disease dementia, and two with the behavioral variant of frontotemporal dementia), who had suffered further cognitive deterioration following COVID-19.

Lead investigators Souvik Dubey, MD, DM, from the Department of Neuromedicine, Bangur Institute of Neurosciences (BIN), Kolkata, West Bengal, India, and Julián Benito-León, MD, Ph.D., from the Department of Neurology, University Hospital "12 de Octubre," Madrid, Spain, explained, "We speculated there must have been some deleterious effect of COVID-19 in patients with preexisting dementia extrapolating our understanding from the cognitive impact of this viral infection in patients without dementia. However, post-COVID-19 evaluation of cognitive impairments in patients with preexisting dementia is difficult due to multiple confounders and biases."

In addition to finding that that all subtypes of dementia, irrespective of patients' previous dementia types, behaved like rapidly progressive dementia following COVID-19, the team of investigators found that the line of demarcation between different types of dementia became remarkably blurry post-COVID-19.

Co-investigator Ritwik Ghosh, MD, Department of General Medicine, Burdwan Medical College and Hospital, Burdwan, West Bengal, India, expressed his concern about dementia subtyping. "It is more difficult in the post-COVID-19 era, where the history of this viral infection plays the most important role. Few patients with a history of COVID-19 without preexisting dementia have phenotypically and imaging-wise similar brain changes mimicking other degenerative and vascular dementias."

Researchers also found that the characteristics of a particular type of dementia changed following COVID-19, and both degenerative and vascular dementias started behaving like mixed dementia both clinically and radiologically. A rapidly and aggressively deteriorating course was observed in patients having insidious onset, slowly progressive dementia, and who were previously cognitively stable.

Cortical atrophy was also evident in the study's subsequent follow-ups. Coagulopathy involving small vessels and inflammation, which were further correlated with white matter intensity changes in the brain, was considered the most important pathogenetic indicator.

The rapid progression of dementia, the addition of further impairments/deterioration of cognitive abilities, and the increase or new appearance of white matter lesions suggest that previously compromised brains have little defense to withstand a new insult (i.e., a "second hit" like infection/dysregulated immune response and inflammation).

According to Dr. Dubey and his co-investigators, "'Brain fog' is an ambiguous terminology without specific attribution to the spectrum of post-COVID-19 cognitive sequelae. Based on the progression of cognitive deficits and the association with white matter intensity changes, we propose a new term: 'FADE-IN MEMORY' (i.e., Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment)."

Co-investigator Mahua Jana Dubey, MD, Department of Psychiatry, Berhampur Mental Hospital, Berhampur, West Bengal, India, added, "Amidst various psychosocial impacts of COVID-19, cognitive deficits, when accompanied by depression and/or apathy and fatigue in patients with or without preexisting dementia, require meticulous evaluation because it imposes added stress and burden on caregivers, one of the most important but often forgotten issues that may have the potential to hamper treatment."

"As the aging population and dementia are increasing globally, we believe pattern recognition of COVID-19-associated cognitive deficits is urgently needed to distinguish between COVID-19-associated cognitive impairments per se and other types of dementia. This understanding will have a definitive impact on future dementia research," Dr. Souvik Dubey concluded.

"Increasing epidemiological evidence of the association of COVID-19 and AD is the heightened risk of AD with COVID-19, and of increased COVID-19 in patients with AD points to shared pathogenesis. Dubey et al further clarify this connection in demonstrating COVID-19 fundamentally alters the course of dementia no matter the cause," remarked George Perry, Ph.D., Editor-in-Chief, Journal of Alzheimer's Disease, and Semmes Distinguished University Chair in Neurobiology at The University of Texas at San Antonio.

More information: Souvik Dubey et al, The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia, Journal of Alzheimer's Disease Reports (2023). DOI: 10.3233/ADR-220090

Provided by IOS Press 

 

Study: ChatGPT has potential to help cirrhosis, liver cancer patients

by Cedars-Sinai Medical Center

Credit: Pixabay/CC0 Public Domain

A new study by Cedars-Sinai investigators describes how ChatGPT, an artificial intelligence (AI) chatbot, may help improve health outcomes for patients with cirrhosis and liver cancer by providing easy-to-understand information about basic knowledge, lifestyle and treatments for these conditions.

09 april 2023--The findings, published in the peer-reviewed journal Clinical and Molecular Hepatology, highlights the AI system's potential to play a role in clinical practice.

"Patients with cirrhosis and/or liver cancer and their caregivers often have unmet needs and insufficient knowledge about managing and preventing complications of their disease," said Brennan Spiegel, MD, MSHS, director of Health Services Research at Cedars-Sinai and co-corresponding author of the study. "We found ChatGPT—while it has limitations—can help empower patients and improve health literacy for different populations."

Patients diagnosed with liver cancer and cirrhosis, an end-stage liver disease that is also a major risk factor for the most common form of liver cancer, often require extensive treatment that can be complex and challenging to manage.

"The complexity of the care required for this patient population makes patient empowerment with knowledge about their disease crucial for optimal outcomes," said Alexander Kuo, MD, medical director of Liver Transplantation Medicine at Cedars-Sinai and co-corresponding author of the study. "While there are currently online resources for patients and caregivers, the literature available is often lengthy and difficult for many to understand, highlighting the limited options for this group."

Personalized education AI models could help increase patient knowledge and education, noted Kuo.

One of those is ChatGPT, which stands for generative pre-trained transformer. It has quickly become popular for its human-like text in chatbot conversations where users can input any prompt and it will generate a response based on the information stored in its database.

It has already shown some potential for medical professionals by writing basic medical reports and correctly answering medical student examination questions.

"ChatGPT has shown to be able to provide professional, yet highly comprehensible responses," said Yee Hui Yeo, MD, first author of the study and a clinical fellow in the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. "However, this is one of the first studies to examine the ability of ChatGPT to answer clinically oriented, disease-specific questions correctly and compare its performance to physicians and trainees."

To verify the accuracy of the AI model in its knowledge about both cirrhosis and liver cancer, investigators presented ChatGPT with 164 frequently asked questions in five categories. The ChatGPT answers were then graded independently by two liver transplant specialists.

Each question was posed twice to ChatGPT and was categorized as either basic knowledge, diagnosis, treatment, lifestyle or preventive medicine.

Study results include:

• ChatGPT answered about 77% of the questions correctly, providing high levels of accuracy in 91 questions from a variety of categories.
• The specialists grading the responses said 75% of the responses for basic knowledge, treatment and lifestyle were comprehensive or correct, but inadequate.
• The proportion of responses that were "mixed with correct and incorrect data" was 22% for basic knowledge, 33% for diagnosis, 25% for treatment, 18% for lifestyle and 50% for preventive medicine.

The AI model also provided practical and useful advice to patients and caregivers regarding the next steps adjusting to a new diagnosis.

Still, the study left no doubt that advice from a physician was superior.

"While the model was able to demonstrate strong capability in the basic knowledge, lifestyle and treatment domains, it suffered on the ability to provide tailored recommendations according to the region where the inquirer lived," said Yeo. "This is most likely due to the varied recommendations in liver cancer surveillance interval and indications reported by different professional societies. But we are hopeful that it will be more accurate in addressing the questions according to the inquirers' location."

"More research is still needed to better examine the tool in patient education, but we believe ChatGPT to be a very useful adjunctive tool for physicians—not a replacement—but adjunctive tool that provides access to reliable and accurate health information that is easy for many to understand," Spiegel said. "We hope that this can help physicians to empower patients and improve health literacy for patients facing challenging conditions such as cirrhosis and liver cancer."

Other Cedars-Sinai authors are Jamil Samaan, Hirsh Trivedi, Aarshi Vipani, Walid Ayoub, Ju Dong Yang and Omer Liran.

More information: Yee Hui Yeo et al, Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma, Clinical and Molecular Hepatology (2023). DOI: 10.3350/cmh.2023.0089

Provided by Cedars-Sinai Medical Center 

 

Alzheimer's: New study supports amyloid hypothesis but suggests alternative treatment

by Columbia University

CREB3L2-ATF4 up-regulation in β-amyloid pathology 5xFAD model. In vivo detection and quantification of CREB3L2-ATF4 dimers by PLA in the dentate gyrus of 10-week-old 5xFAD or wild-type hippocampus. ML, molecular layer; IPL, inner polymorphic layer; GCL, granule cell layer. Wild-type (WT), n = 6; 5xFAD, n = 5; ML, *P = 0.0182; GCL, P = 0.0574; IPL, *P = 0.0285; unpaired one-tailed t tests. Whiskers extend to the smallest and largest data values, and sample means are indicated by + sign. Scale bar, 10 μm. Credit: Science Advances (2023). DOI: 10.1126/sciadv.add2671

An analysis of human brain cells provides new evidence in support of the "amyloid hypothesis," the prevailing idea that Alzheimer's is caused by the accumulation of beta-amyloid proteins in the brain.

09 april 2023--In the study, Columbia University researchers found that amyloid sparks an alliance between two proteins in the brain's neurons and this pairing is linked to about half of the gene changes that are known to occur in the disease, triggering the rapid accumulation of tau proteins, a primary driver of neurodegeneration in the disease.

"This protein pair seems very central to the disease, and because it does not appear to have another function in the brain, it is a good target for a new therapy," says the study's senior author, Ulrich Hengst, Ph.D., associate professor of pathology & cell biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at the Columbia University Vagelos College of Physicians and Surgeons.

Protein pair was hidden to previous research

The researchers found the pair when they were looking for proteins that spark hundreds of changes in gene activity that occur in brain cells during Alzheimer's disease. "Our thought was that if we can interfere with the proteins and prevent those changes, we can prevent the disease," says Cláudio Gouveia Roque, Ph.D., associate research scientist in the Hengst lab, who conducted the study.

Instead of looking for proteins that act alone, the researchers looked for pairs of different proteins working together.

"We know this type of protein necessarily works in pairs, but previous Alzheimer's research hadn't looked for specific pairs. Consequently, our understanding of the changes underlying Alzheimer's progression has been fragmented and incomplete," says Hengst. "And because of that, we've most likely missed therapeutic opportunities."

Amyloid causes proteins to stick together

The search by Hengst and Gouveia Roque, together with a previous associate research scientist in the Hengst lab, Jimena Baleriola, uncovered two proteins—ATF4 and CREB3L2—whose binding to each other is triggered by amyloid and that together interact with about 50% of the gene expression changes that occur in brain cells during Alzheimer's disease.

Once formed, the CREB3L2-ATF4 pair activates a network of other proteins that cause deadly tau deposits to accumulate inside neurons. The protein pair also disables the cellular machinery that clears old and damaging proteins from neurons, another hallmark of Alzheimer's.

Although CREB3L2 and ATF4 are also found alone in healthy neurons, their binding together is greatly increased in the presence of a stress like excess amyloid, the researchers found.

"These two proteins are like two teenage boys," says Hengst. "Individually, they may be relatively harmless. But if you put them together without a responsible adult in the room, they're likely to be up to no good."

New treatment approach

The findings suggest that Alzheimer's could be treated by interfering with the CREB3L2-ATF4 pair.

"Normally, proteins that control gene activity are very poor drug targets because they control too many genes. But by targeting this pair we might be able to preserve the function of the two individual proteins while preventing the bad effects of them binding together," Hengst says.

Hengst and Gouveia Roque have already identified a drug, dovitinib, that interferes with the effects of the protein pair. Dovitinib has been approved by the FDA for the treatment of renal cancer but has not been tested for the treatment of Alzheimer's. "Nonetheless, the drug is not toxic to neurons and crosses the blood-brain barrier, so this bodes well for future drug development," Hengst says.

"We're not talking about getting rid of amyloid with this approach," adds Gouveia Roque. "If we can interfere with the protein pair, we could slow or perhaps even stop the progression of the disease. Yes, there would still be amyloid in the brain, but the neurons would react far less to it. One could hypothesize that such a drug could be used in combination with an amyloid-reducing drug for even greater effect."

The paper is published in the journal Science Advances.

More information: Cláudio Gouveia Roque et al, CREB3L2-ATF4 heterodimerization defines a transcriptional hub of Alzheimer's disease gene expression linked to neuropathology, Science Advances (2023). DOI: 10.1126/sciadv.add2671

Provided by Columbia University 

 

8,000 steps once or twice a week cuts mortality risk: Study

Credit: Unsplash/CC0 Public Domain

Walking 8,000 steps—about four miles (6.4 kilometers)—one or two days a week may significantly reduce the risk of an early death, according to a study released on Tuesday.

09 april 2023--While regular exercise is known to lower mortality risk, the study published in the journal JAMA Network Open looked at the health benefits of walking intensively only a few days a week.

For the study, the researchers from Kyoto University and the University of California, Los Angeles analyzed data from 3,100 American adults.

They found that those who walked 8,000 steps or more one or two days a week were 14.9 percent less likely to die over a 10-year period than those who never reached that mark.

For those who walked 8,000 steps or more three to seven days a week, the mortality risk was even lower—16.5 percent.

The health benefits of walking 8,000 steps or more one or two days a week appeared higher for participants aged 65 years and older.

"The number of days per week taking 8,000 steps or more was associated with a lower risk of all-cause and cardiovascular mortality," the researchers said.

"These findings suggest that individuals may receive substantial health benefits by walking just a couple of days a week."

For the study, the researchers used daily step counts from the 3,100 participants in 2005 and 2006 and examined their mortality data 10 years later.

Among the participants, 632 took 8,000 steps or more zero days a week, 532 took 8,000 steps or more one to two days a week and 1,937 took 8,000 or more steps three to seven days a week.

The average American walks 3,000-4,000 steps a day, according to the Mayo Clinic, which says walking for regular activity can reduce the risk of heart disease, obesity, diabetes, high blood pressure and depression.

More information: Kosuke Inoue et al, Association of Daily Step Patterns With Mortality in US Adults, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.5174

Journal information: JAMA Network Open 

 

Researchers identify specific regions of the brain damaged by high blood pressure, involved in mental decline, dementia

by European Society of Cardiology

3D reconstruction show how high systolic blood pressure has affected the main tracts of white matter in the brain. The red shows the areas most affected by high blood pressure while the yellow areas are also affected but to a lesser extent. The study shows that high systolic blood pressure causes damage to the white matter and its connections with other parts of the brain and this is linked to worse cognitive functions in the people analysed. For the first time, specific brain areas which are the culprit of this disease are identified. Credit: (c) Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy. (used with permission)

For the first time, researchers have identified specific regions of the brain that are damaged by high blood pressure and may contribute to a decline in mental processes and the development of dementia.

09 april 2023--High blood pressure is known to be involved in causing dementia and damage to brain function. The study, which is published in the European Heart Journal today, shows how this happens. It gathered information from a combination of magnetic resonance imaging (MRI) of brains, genetic analyses and observational data from thousands of patients to look at the effect of high blood pressure on cognitive function. The researchers then checked their findings in a separate, large group of patients in Italy.

Tomasz Guzik, Professor of Cardiovascular Medicine at the University of Edinburgh (UK) and Jagiellonian University Medical College, Krakow (Poland), who led the research, said, "By using this combination of imaging, genetic and observational approaches, we have identified specific parts of the brain that are affected by increases in blood pressure, including areas called the putamen and specific white matter regions. We thought these areas might be where high blood pressure affects cognitive function, such as memory loss, thinking skills and dementia. When we checked our findings by studying a group of patients in Italy who had high blood pressure, we found that the parts of the brain we had identified were indeed affected.

"We hope that our findings may help us to develop new ways to treat cognitive impairment in people with high blood pressure. Studying the genes and proteins in these brain structures could help us understand how high blood pressure affects the brain and causes cognitive problems. Moreover, by looking at these specific regions of the brain, we may be able to predict who will develop memory loss and dementia faster in the context of high blood pressure. This could help with precision medicine, so that we can target more intensive therapies to prevent the development of cognitive impairment in patients most at risk."

High blood pressure is common and occurs in 30% of people worldwide, with an additional 30% showing the initial stages of the disease. Studies have shown that it affects how well the brain works and that it can cause long-term changes. However, until now it was not known exactly how high blood pressure damages the brain and which specific regions are affected.

Prof. Guzik and an international team of researchers used brain MRI imaging data from over 30,000 participants in the UK Biobank study, genetic information from genome-wide association studies (GWAS) from UK Biobank and two other international groups (COGENT and the International Consortium for Blood Pressure), and a technique called Mendelian randomization, to see if high blood pressure was actually the cause of changes to specific parts of the brain rather than just being associated with these changes.

"Mendelian randomization is a way of using genetic information to understand how one thing affects another," said Prof. Guzik. "In particular, it tests if something is potentially causing a certain effect, or if the effect is just a coincidence. It works by using a person's genetic information to see if there is a relationship between genes predisposing to higher blood pressure and outcomes. If there is a relationship, then it is more likely that the high blood pressure is causing the outcome. This is because genes are randomly passed down from parents, so they are not influenced by other factors that could confuse the results. In our study, if a gene that causes high blood pressure is also linked to certain brain structures and their function, then it suggests that high blood pressure might really be causing brain dysfunction at that location, leading to problems with memory, thinking and dementia."

The researchers found changes to nine parts of the brain were related to higher blood pressure and worse cognitive function. These included the putamen, which is a round structure in the base of the front of the brain, responsible for regulating movement and influencing various types of learning. Other areas affected were the anterior thalamic radiation, anterior corona radiata and anterior limb of the internal capsule, which are regions of white matter that connect and enable signaling between different parts of the brain. The anterior thalamic radiation is involved in executive functions, such as the planning of simple and complex daily tasks, while the other two regions are involved in decision-making and the management of emotions.

The changes to these areas included decreases in brain volume and the amount of surface area on the brain cortex, changes to connections between different parts of the brain, and changes in measures of brain activity.

The first author of the study, Associate Professor Mateusz Siedlinski, also a researcher at Jagiellonian University Medical College, said, "Our study has, for the first time, identified specific places in the brain that are potentially causally associated with high blood pressure and cognitive impairment. This was uniquely possible thanks to the availability of data from UK Biobank, including MRI brain images, and thanks to previous research identifying genetic variants that affect the structure and function of over 3000 areas of the brain."

Co-author of the study Professor Joanna Wardlaw, Head of Neuroimaging Sciences at the University of Edinburgh, said, "It has been known for a long time that high blood pressure is a risk factor for cognitive decline, but how high blood pressure damages the brain was not clear. This study shows that specific brain regions are at particularly high risk of blood pressure damage, which may help to identify people at risk of cognitive decline in the earliest stages, and potentially to target therapies more effectively in future."

Limitations of the study include that participants in the UK Biobank study are mainly white and middle-aged, so it might not be possible to extrapolate the findings to older people.

An accompanying editorial is written by Dr. Ernesto Schiffrin, from Sir Mortimer B. Davis-Jewish General Hospital and McGill University, Montreal, (Canada), and Dr. James Engert, from the McGill University Health Centre Research Institute, Montreal. They observe that "further mechanistic studies of the effects of BP [blood pressure] on cognitive function are required to determine precise causal pathways and relevant brain regions."

They also highlight one of the study's findings about systolic and diastolic blood pressure (SBP and DBP): "Perhaps one of the more interesting results in this study is the possible distinct causal effects of SBP vs. DBP. The authors observed some overlapping results for SBP and DBP on cognitive function when analyzed in isolation. However, when each parameter is analyzed after adjusting for the other, or in multivariable models, intriguing findings begin to emerge. DBP alone does not predict a decline in cognitive function, but in fact, is protective when adjusted for SBP. This result was true both observationally and when using Mendelian randomization," they write, and continue by discussing the possible reasons for this.

More information: Tomasz J Guzik et al, Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure, European Heart Journal (2023). DOI: 10.1093/eurheartj/ehad101

Ernesto L. Schiffrin et al, Hypertension, brain imaging phenotypes and cognitive impairment: lessons from Mendelian randomisation, European Heart Journal (2023). DOI: 10.1093/eurheartj/ehad187

Provided by European Society of Cardiology 

 

Looking for cancer information: Can ChatGPT be counted on?

by Huntsman Cancer Institute

Credit: Pixabay/CC0 Public Domain

A study in the Journal of The National Cancer Institute Cancer Spectrum looked at chatbots and artificial intelligence (AI), as they become popular resources for cancer information. They found these resources give accurate information when asked about common cancer myths and misconceptions. In the first study of its kind, Skyler Johnson, MD, physician-scientist at Huntsman Cancer Institute and assistant professor in the department of radiation oncology at the University of Utah (the U), evaluated the reliability and accuracy of ChatGPT's cancer information.

09 april 2023--Using the National Cancer Institute's (NCI) common myths and misconceptions about cancer, Johnson and his team found that 97% of the answers were correct. However, this finding comes with some important caveats, including a concern amongst the team that some of the ChatGPT answers could be interpreted incorrectly. "This could lead to some bad decisions by cancer patients. The team suggested caution when advising patients about whether they should use chatbots for information about cancer," says Johnson.

The study found reviewers were blinded, meaning they didn't know whether the answers came from the chatbot or the NCI. Though the answers were accurate, reviewers found ChatGPT's language was indirect, vague, and in some cases, unclear.

"I recognize and understand how difficult it can feel for cancer patients and caregivers to access accurate information," says Johnson. "These sources need to be studied so that we can help cancer patients navigate the murky waters that exist in the online information environment as they try to seek answers about their diagnoses."

Incorrect information can harm cancer patients. In a previous study by Johnson and his team published in the Journal of the National Cancer Institute, they found that misinformation was common on social media and had the potential to harm cancer patients.

The next steps are to evaluate how often patients are using chatbots to seek out information about cancer, what questions they are asking, and whether AI chatbots provide accurate answers to uncommon or unusual questions about cancer.

More information: Skyler B Johnson et al, Using ChatGPT to evaluate cancer myths and misconceptions: artificial intelligence and cancer information, JNCI Cancer Spectrum (2023). DOI: 10.1093/jncics/pkad015

Skyler B Johnson et al, Cancer Misinformation and Harmful Information on Facebook and Other Social Media: A Brief Report, JNCI: Journal of the National Cancer Institute (2021). DOI: 10.1093/jnci/djab141

Provided by Huntsman Cancer Institute

 

Frequent socializing linked to longer lifespan of older people

by British Medical Journal

Credit: CC0 Public Domain

Frequent socializing may extend the lifespan of older people, suggests a study of more than 28,000 Chinese people, published online in the Journal of Epidemiology & Community Health.

09 april 2023--Socializing nearly every day seems to be the most beneficial for a long life, the findings suggest.

In 2017, 962 million people around the globe were over 60, and their number is projected to double by 2050. Consequently, considerable attention has focused on the concept of "active" or "successful" aging, an important component of which seems to be an active social life, note the researchers.

But most of the evidence for the health benefits of socializing is based on people in Western countries, with little published data on people in Asia.

To try and plug this knowledge gap, the researchers wanted to explore whether the frequency of socializing might be linked to overall survival in a relatively large group of older people living in China.

They drew on participants of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), an ongoing, prospective nationally representative study of older people living independently, which began in 1998.

Information on the frequency of socializing only started being collected in 2002, and the current study focuses on 5 separate waves of data collection up to 2018-19, involving a total of 28,563 participants with an average age of 89.

Participants were asked how often they engaged in social activities: almost every day; at least once a week; at least once a month; occasionally; and never. Information on potentially influential factors was also collected, including sex, education, marital status; household income; fruit and vegetable intake; lifestyle; and poor health.

Survival was tracked for an average of 5 years or until death.

Over the first 5 years 25,406 people said they didn't engage in any social activities; 1,379 reported doing so sometimes; 693 at least once a month; 553 at least once a week; and 532 almost daily.

During the entire monitoring period, 21,161 (74%) participants died, 15,728 of whom died within the first 5 years.

Overall, more frequent social activity was associated with significantly longer survival. The greater the frequency, the greater the likelihood of living longer.

Up to 5 years from the start of the monitoring period standardized death rates were 18.4 per 100 people monitored for a year among those who never socialized; 8.8 among those who did so occasionally; 8.3 among those who did so at least monthly; 7.5 among those who socialized at least once a week; and 7.3 among those who did so nearly every day.

Time to death was delayed by 42% in those who socialized occasionally, by 48% in those who did at least monthly, by 110% in those who did so at least weekly, and by 87% in those who did so nearly every day, compared with those who said they never socialized.

After 5 years, the survivors included 8,420 people who said they never socialized, 688 who did so occasionally, 350 who did so at least monthly, 295 who did so at least weekly, and 272 who did so nearly every day.

Standardized death rates were 6.2 per 100 people monitored for a year among those who never socialized; 4.8 among those who did so occasionally; 5 among those socializing at least once a month; 5.4 among those doing so at least once a week; and 3.6 among those who did so nearly every day.

A threshold effect was evident: Only socializing nearly every day was associated with significantly longer survival in this group among whom time to death was delayed by 204%.

Factors associated with being more socially active were male sex, younger age, a higher level of education, marriage, living in a town/city and/or with relatives, and actual/self-rated good health.

When the data were further stratified by age, social activity seemed to be even more strongly associated with extended survival within the first 5 years for the oldest old, suggesting that strategies to promote the maintenance of an active social life in very old people, should be encouraged, say the researchers.

This is an observational study, so can't establish cause. And the researchers acknowledge they weren't able to include possible changes in socializing or health behaviors over time.

Nor is it clear exactly why socializing in older age might extend survival. The explanations mooted include enhancing healthy behaviors, such as more physical activity and a better diet. Socializing may also mitigate the impact of chronic stressors, say the researchers.

"In our study, although the association between social activity frequency and overall survival attenuated after adjusting for sociodemographic factors, socioeconomic status, healthy behaviors and several morbidities, it still remained statistically significant, which indicated that social activity participation per se was an independent predictor for overall survival in older people," they conclude.

More information: Association between social activity frequency and overall survival in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), Journal of Epidemiology & Community Health (2023). DOI: 10.1136/jech-2022-219791

Provided by British Medical Journal