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Severe Covid-19 linked with molecular signs of brain ageing

Scientists have emphasised the importance of neurological follow-up in patients who have recovered from Covid-19.

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Scientists have found similarities between biological pathways in the ageing brain and in patients affected by serve Covid-19 infection.

Although Covid-19 is primarily a respiratory disease, neurological symptoms have been described in many Covid-19 patients, including in recovered individuals. 

Patients report symptoms including brain fog or lack of focused thinking, memory loss and depression, and scientists have demonstrated that patients with severe Covid-19 exhibit a drop in cognitive performance that mimics accelerated ageing. 

But, the molecular evidence for Covid-19’s ageing effects on the brain is lacking.

In a series of experiments, scientists at Beth Israel Deaconess Medical Center (BIDMC), found that gene usage in the brains of patients with Covid-19 is similar to those observed in ageing brains. 

Using a molecular profiling technique called RNA sequencing to measure the levels of every gene expressed in a particular tissue sample, the scientists assessed changes in gene expression profiles in the brains of Covid-19 patients and compared them to those changes observed in the brains of uninfected individuals. 

The team’s analysis, published in Nature Aging, suggested that many biological pathways that change with natural ageing in the brain also changed in patients with severe Covid-19.

“Ours is the first study to show that Covid-19 is associated with the molecular signatures of brain ageing,” said co-first and co-corresponding author Maria Mavrikaki, PhD, an instructor of pathology at BIDMC and Harvard Medical School. 

“We found striking similarities between the brains of patients with Covid-19 and aged individuals.”

Mavrikaki and colleagues analysed a total of 54 postmortem human frontal cortex tissue samples from adults 22 to 85 years old. Of these, 21 samples were from severe Covid-19 patients and one from an asymptomatic Covid-19 patient who died. These samples were age- and sex-matched to uninfected controls with no history of neurological or psychiatric disease. 

The scientists also included an age-and sex- matched uninfected Alzheimer’s disease case for analysis as a control to a Covid-19 case which had co-morbid Alzheimer’s disease, as well as an additional independent control group of uninfected individuals with a history of intensive care or ventilator treatment.

“We observed that gene expression in the brain tissue of patients who died of Covid-19 closely resembled that of uninfected individuals 71-years-old or older,” said co-first author Jonathan Lee, PhD, a postdoctoral research fellow at BIDMC and Harvard Medical School.

“Genes that were upregulated in ageing were upregulated in the context of severe COVID-19; likewise, genes downregulated in ageing were also downregulated in severe Covid-19. While we did not find evidence that the SARS-CoV-2 virus was present in the brain tissue at the time of death, we discovered inflammatory patterns associated with Covid-19. This suggests that this inflammation may contribute to the ageing-like effects observed in the brains of patients with Covid-19 and long covid.”

Senior and co-corresponding author Frank Slack, PhD, director of the Institute for RNA Medicine at BIDMC and the Shields Warren Mallinckrodt Professor of Medical Research at Harvard Medical School, said: “Given these findings, we advocate for neurological follow-up of recovered Covid-19 patients.

“We also emphasise the potential clinical value in modifying the factors associated with the risk of dementia — such as controlling weight and reducing excessive alcohol consumption — to reduce the risk or delay the development of ageing-related neurological pathologies and cognitive decline.”

Better understanding of the molecular mechanisms underlying brain ageing and cognitive decline in Covid-19 could lead to the development of novel therapeutics to address cognitive decline observed in Covid-19 patients. 

The team is now trying to understand what drives the ageing-like effects in the brains of Covid-19 patients. 

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Air pollution linked to increased hospital admission for heart and lung diseases

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Exposure to fine particulate matter (PM2.5) air pollution is linked to an increased risk of hospital admission for major heart and lung diseases, find two large US studies, published by The BMJ.

Together, the results suggest that no safe threshold exists for heart and lung health.

According to the Global Burden of Disease study, exposure to PM2.5 accounts for an estimated 7.6% of total global mortality and 4.2% of global disability adjusted life years (a measure of years lived in good health).

In light of this extensive evidence, the World Health Organization (WHO) updated the air quality guidelines in 2021, recommending that an annual average PM2.5 levels should not exceed 5 μg/m3 and 24 hour average PM2.5 levels should not exceed 15 μg/m3 on more than 3-4 days each year.

In the first study, researchers linked average daily PM2.5 levels to residential zip codes for nearly 60 million US adults (84 per cent white, 55 per cent women) aged 65 and over from 2000 to 2016. They then used Medicare insurance data to track hospital admissions over an average of eight years.

After accounting for a range of economic, health and social factors, average PM2.5 exposure over three years was associated with increased risks of first hospital admissions for seven major types of cardiovascular disease – ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, and thoracic and abdominal aortic aneurysms.

Compared with exposures of 5 μg/m3 or less (the WHO air quality guideline for annual PM2.5), exposures between 9 and 10 μg/m3, which encompassed the US national average of 9.7 μg/m3 during the study period, were associated with a 29% increased risk of hospital admission for cardiovascular disease.

On an absolute scale, the risk of hospital admission for cardiovascular disease increased from 2.59% with exposures of 5 μg/m3 or less to 3.35% at exposures between 9 and 10 μg/m3.

“This means that if we were able to manage to reduce annual PM2.5 below 5 µg/m3, we could avoid 23% in hospital admissions for cardiovascular disease,” say the researchers.*

These cardiovascular effects persisted for at least three years after exposure to PM2.5, and susceptibility varied by age, education, access to healthcare services, and area deprivation level.

The researchers say their findings suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health, and that substantial benefits could be attained through adherence to the WHO air quality guideline.

“On February 7, 2024, the US Environmental Protection Agency (EPA) updated the national air quality standard for annual PM2.5 level, setting a stricter limit at no more than 9 µg/m3. This is the first update since 2012. However, it is still considerably higher than the 5 µg/m3 set by WHO. Obviously, the newly published national standard was not sufficient for the protection of public health,” they add.*

In the second study, researchers used county-level daily PM2.5 concentrations and medical claims data to track hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease for 50 million US adults aged 18 and over from 2010 to 2016.

During the study period, more than 10 million hospital admissions and 24 million emergency department visits were recorded.

They found that short term exposure to PM2.5, even at concentrations below the new WHO air quality guideline limit, was statistically significantly associated with higher rates of hospital admissions for natural causes, cardiovascular disease and respiratory disease, as well as emergency department visits for respiratory disease.

For example, on days when daily PM2.5 levels were below the new WHO air quality guideline limit of 15 μg/m3, an increase of 10 μg/m3 in PM2.5 was associated with 1.87 extra hospital admissions per million adults aged 18 and over per day.

The researchers say their findings constitute an important contribution to the debate about the revision of air quality limits, guidelines, and standards.

Both research teams acknowledge several limitations such as possible misclassification of exposure and point out that other unmeasured factors may have affected their results. What’s more, the findings may not apply to individuals without medical insurance, children and adolescents, and those living outside the US.

However, taken together, these new results provide valuable reference for future national air pollution standards.

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Home health care linked to increased hospice use at end-of-life – study

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Patients who had previously received home health care had a higher likelihood of accessing hospice care at the end of their life, according to a new study.

Researchers, whose findings are published in the Journal of Palliative Medicine, examined the home health care and hospice care experiences of more than two million people.

Using Medicare data, researchers found when individuals received home health care before the last year of their life, they had higher odds of using hospice care than those who had never received home health care.

Researchers said this association underscores the potential benefits of receiving end-of-life care in the comfort of one’s home.

As the aged population increases, the findings also show the need for more resources in the health care sector and staff training in end-of-life care.

Home health care services including skilled nursing, therapy, social work and aide services are used to maintain functioning or slow decline in health. Hospice care provides similar services but is intended for those with life expectancies of six months or less and is focused on pain relief, minimising hospital visits and providing comfort and support. Both services provide patients the opportunity to receive more personalised care in their home.

Researchers say home-based care also encourages greater involvement of family caregivers in the caregiving process.

Olga Jarrín, senior author of the study, the Hunterdon Professor of Nursing Research at the Rutgers School of Nursing and director of the Community Health and Aging Outcomes Laboratory within the Rutgers Institute for Health, Health Care Policy and Aging Research, commented: “In addition to benefits for the patient, hospice care also provides resources and support to help family caregivers cope with the physical, emotional and practical challenges of caring for a loved one at the end of life.”

Hyosin (Dawn) Kim, research assistant professor at Oregon State University and first author of the study, added: “By providing personalised care, reducing hospitalisations, fostering family involvement and support, and improving symptom management, home-based care can enhance the quality of end-of-life experiences for patients with terminal illnesses and their families.”

 

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Sleep programme shows promise in those with memory problems – study

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A new study has shown promising results in improving sleep and quality of life in individuals living with memory problems.

A group of researchers from Penn Nursing, Penn Medicine, Rutgers School of Nursing, and Drexel University’s College of Nursing and Health Professions, have delved into the efficacy of a non-pharmacological approach in a trial known as the Healthy Patterns Sleep Program.

The study involved 209 pairings of community-residing individuals with memory problems and their care partners. Participants were assigned to either the Healthy Patterns Sleep Program, which consisted of one-hour home activity sessions administered over four weeks, or a control group that received sleep hygiene training, plus education on home safety and health promotion.

The Healthy Patterns Sleep Program trained care partners in timed daily activities such as reminiscence in the morning, exercise in the afternoon and sensory activities in the evening that can decrease daytime sleepiness and improve nighttime sleep quality.

Nancy Hodgson, PhD, RN, FAAN, the Claire M. Fagin Leadership Professor in Nursing and Chair of Department of Biobehavioral Health Sciences, who led the study, said: “The results from this study provide fundamental new knowledge regarding the effects of timing activity participation and can lead to structured, replicable treatment protocols to address sleep disturbances. Overall, the Healthy Patterns program resulted in improved QOL compared to an attention-control group.”

The findings also indicate that, compared to a control group, the four-week Healthy Patterns program improved sleep quality among persons living with memory issues who had depressive symptoms or poor sleep quality.  The study indicates the Healthy Patterns Intervention might need a longer dose to induce improvements in other sleep-wake activity metrics.

The study’s significance lies in its confirmation of the effectiveness of behavioural interventions in not only improving quality of life and addressing sleep quality issues in this population, but also potentially reducing care partner burden and overall care costs for persons living at home with memory problems.

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