Keeping the aging brain connected with words and music

by Vibhav Nandagiri, Duke Research Blog

Relative location of subcortical white matter fiber tracts (lateral view). Credit: Wikipedia

In an era of seemingly endless panaceas for age-based mental decline, navigating through the clutter can be a considerable challenge.

29 jan 2022--However, a team of Duke researchers, led by cognitive neuroscientist Edna Andrews, Ph.D., think they may have found a robust and long-term solution to countering this decline and preventing pathologies in an aging brain. Their approach does not require an invasive procedure or some pharmacological intervention, just a good ear, some sheet music, and maybe an instrument or two.

In early 2021, Andrews and her team published one of the first studies to look at musicianship's impact in building cognitive brain reserve. Cognitive brain reserve, simply put, is a way to qualify the resilience of the brain in the face of various pathologies. High levels of cognitive reserve can help stave off dementia, Parkinson's disease or multiple sclerosis for years on end. These levels are quantified through structural measurements of gray matter and white matter in the brain. The white matter may be thought of as the insulated wiring that helps different areas of the brain communicate.

In this particular study, Andrews' team focused on measurements of white matter integrity through an advanced MRI technique known as diffusion tensor imaging, to see what shape it is in.

Previous neuroimaging studies have revealed that normal aging leads to a decrease in white matter integrity across the brain. Over the past fifteen years, however, researchers have found that complex sensory-motor activities may be able to slow down and even reverse the loss of white matter integrity. The two most robust examples of complex sensory-motor activities are multilingualism and musicianship.

Andrews has long been fascinated by the brain and languages. In 2014, she published one of the seminal texts in the field of cognitive neurolinguistics where she laid the groundwork for a new neuroscience model of language. Around the same time, she published the first and to-date only longitudinal fMRI study of second language acquisition. Her findings, built upon decades of research in cognitive neuroscience and linguistics, served as the foundation for her popular FOCUS course: Neuroscience/Human Language.

In more recent years, she has shifted her research focus to understanding the impact of musicianship on cognitive brain reserve. Invigorated by her lived experience as a professional musician and composer, she wanted to see whether lifelong musicianship could increase white matter integrity as one ages. She and her team hypothesized that musicianship would increase white matter integrity in certain fiber tracts related to the act of music-making

To accomplish this goal, she and her team scanned the brains of eight different musicians ranging in age from 20 years to 67 years old. These musicians dedicated an average of three hours per day to practice and had gained years' worth of performance experience. After participants were placed into the MRI machine, the researchers used diffusion tensor imaging to calculate fractional antisotropy (FA) values for certain white matter fiber tracts. A higher FA value meant higher integrity and, consequently, higher cognitive brain reserve. Andrews and her team chose to observe FA values in two fiber tracts, the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF), based on their relevance to musicianship in previous studies.

Previous studies of the two fiber tracts in non-musicians found that their integrity decreased with age. In other words, the older the participants, the lower their white matter integrity in these regions. After analyzing the anisotropy values via linear regression, they observed a clear positive correlation between age and fractional anisotropy in both fiber tracts. These trends were visible in both tracts of both the left and right hemispheres of the brain. Such an observation substantiated their hypothesis, suggesting that highly proficient musicianship can increase cognitive brain reserve as one ages.

These findings expand the existing literature of lifestyle changes that can improve brain health beyond diet and exercise. Though more demanding, neurological changes resulting from the acquisition and maintenance of language and music capabilities have the potential to endure longer into the life cycle.

Andrews is one of the strongest advocates of lifelong learning, not solely for the satisfaction it brings about, but also for the tangible impact it can have on cognitive brain reserve. Picking up a new language or a new instrument should not be pursuits confined to the young child.

It appears, then, that the kindest way to treat the brain is to throw something new at it. A little bit of practice couldn't hurt either.

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More information: Edna Andrews et al, Effects of Lifelong Musicianship on White Matter Integrity and Cognitive Brain Reserve, Brain Sciences (2021). DOI: 10.3390/brainsci11010067

 

Researchers identify biomarker for depression, antidepressant response

by University of Illinois at Chicago

Credit: Pixabay/CC0 Public Domain

Researchers are one step closer to developing a blood test that provides a simple biochemical hallmark for depression and reveals the efficacy of drug therapy in individual patients.

29 jan 2022--Published in a new proof of concept study, researchers led by Mark Rasenick, University of Illinois Chicago distinguished professor of physiology and biophysics and psychiatry, have identified a biomarker in human platelets that tracks the extent of depression.

The research builds off of previous studies by several investigators that have shown in humans and animal models that depression is consistent with decreased adenylyl cyclase—a small molecule inside the cell that is made in response to neurotransmitters such as serotonin and epinephrine.

"When you are depressed, adenylyl cyclase is low. The reason adenylyl cyclase is attenuated is that the intermediary protein that allows the neurotransmitter to make the adenylyl cyclase, Gs alpha, is stuck in a cholesterol-rich matrix of the membrane—a lipid raft—where they don't work very well," Rasenick said.

The new study, "A Novel Peripheral Biomarker for Depression and Antidepressant Response," published in Molecular Psychiatry, has identified the cellular biomarker for translocation of Gs alpha from lipid rafts. The biomarker can be identified through a blood test.

"What we have developed is a test that can not only indicate the presence of depression but it can also indicate therapeutic response with a single biomarker, and that is something that has not existed to date," said Rasenick, who is also a research career scientist at Jesse Brown VA Medical Center. 

The researchers hypothesize they will be able to use this blood test to determine if antidepressant therapies are working, perhaps as soon as one week after beginning treatment. Previous research has shown that when patients showed improvement in their depression symptoms, the Gs alpha was out of the lipid raft. However, in patients who took antidepressants but showed no improvement in their symptoms, the Gs alpha was still stuck in the raft—meaning simply having antidepressants in the bloodstream was not good enough to improve symptoms.

A blood test may be able to show whether or not the Gs alpha was out of the lipid raft after one week. 

"Because platelets turn over in one week, you would see a change in people who were going to get better. You'd be able to see the biomarker that should presage successful treatment," Rasenick said.

Currently, patients and their physicians have to wait several weeks, sometimes months, to determine if antidepressants are working, and when it is determined they aren't working, different therapies are tried. 

"About 30% of people don't get better—their depression doesn't resolve. Perhaps, failure begets failure and both doctors and patients make the assumption that nothing is going to work," Rasenick said. "Most depression is diagnosed in primary care doctor's offices where they don't have sophisticated screening. With this test, a doctor could say, 'Gee, they look like they are depressed, but their blood doesn't tell us they are. So, maybe we need to re-examine this.'"

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More information: Steven D. Targum et al, A novel peripheral biomarker for depression and antidepressant response, Molecular Psychiatry (2021). DOI: 10.1038/s41380-021-01399-1

 

Five years of high-dose vitamin D did not affect incidence of cardiovascular disease or cancer

by University of Eastern Finland

Credit: CC0 Public Domain

A trial by the University of Eastern Finland found that taking a much higher dose of vitamin D than recommended for five years did not affect total mortality or the incidence of cardiovascular disease or cancer in older men and women.

29 jan 20222--In population studies, low levels of vitamin D in the body have been linked to an increased risk of many chronic diseases as well as premature death. However, it cannot be directly deduced from such observational studies whether the use of vitamin D supplementation can reduce the risk of disease or death. The early 2010s saw the commencement of large-scale vitamin D trials in several countries examining the effects of higher than recommended doses of vitamin D on the risk of developing diseases. One of these was the Finnish Vitamin D Trial (FIND) conducted at the University of Eastern Finland in 2012–2018.

In the FIND trial, 2,495 participants (men 60 years or older and women 65 years or older) were randomized for five years to either the placebo group or the groups that received either 40 or 80 micrograms (1600 or 3200 IU) of vitamin D3 per day. All participants were free of cardiovascular disease and cancer at the start of the trial and were allowed to use their own vitamin D supplement of up to 20 micrograms (800 IU) per day (the recommended intake for this age group at the time when the trial was started). At the beginning and during the trial, research forms were used to collect comprehensive information from the subjects on lifestyle, nutrition, risk factors for and the incidence of diseases. Information on the incidence of diseases and on deaths was also obtained from national health registers. Approximately one fifth of the randomly selected subjects underwent more detailed examinations and provided blood samples.

Majority were not deficient in vitamin D at the start of the trial

During the five years of the trial, 119 participants developed cardiovascular disease, 129 subjects were diagnosed with cancer and 19 died. There was no statistically significant difference in the number of events between the groups. The vitamin D doses proved to be safe as no differences in side effects were observed between the groups. In the sub-sample examined in more detail, the mean blood vitamin D (calcidiol) concentration, was 75 nmol/L (30 ng/mL) at baseline. After one year, the mean calcidiol concentration was 100 nmol/L (40 ng/mL) in the group taking 40 micrograms of vitamin D per day and 120 nmol/L (48 ng/mL) in the group taking 80 micrograms of vitamin D per day. There was no significant change in the calcidiol concentrations in the placebo group. Only 9% of subjects had low vitamin D levels at baseline, i.e. they had a blood calcidiol concentration of less than 50 nmol/L (20 ng/mL).

The findings of the FIND trial are well in line with other similar studies that have shown that taking higher doses of vitamin D than recommended for many years does not have a significant effect on the risk of developing cardiovascular disease or cancer if the body's vitamin D status is already adequate. In Finland, the average vitamin D intake of the population has increased since the early 2000s due to, among other things, the vitamin D supplementation of vegetable oil spreads and liquid dairy products as well as the increased use of vitamin D supplements. Securing one's vitamin D intake with vitamin D supplements is still recommended, especially during the winter, if the diet is low in sources of vitamin D, such as fish or vitamin D-fortified foods. In Finland, vitamin D supplementation of 10 micrograms per day (400 IU) is recommended for the adult population; the recommendation is 20 micrograms per day (800 IU) for those aged 75 and over. However, the study does not support the use of large vitamin D doses for prevention of cardiovascular diseases or cancer.

In addition to these main findings, the FIND trial will provide comprehensive reports on the effects of vitamin D supplementation on, among other things, type 2 diabetes, fractures and falls, mood changes, infections, pain conditions, and other outcomes.

More information: Jyrki K Virtanen et al, Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial—a randomized controlled trial, The American Journal of Clinical Nutrition (2021). DOI: 10.1093/ajcn/nqab419

 

Risk of overactive bladder associated with medications for dementia

by University of Houston

Credit: Unsplash/CC0 Public Domain

A study from the University of Houston College of Pharmacy, published in the Journal of the American Geriatrics Society, has evaluated the risk of overactive bladder (OAB) as a side effect of cholinesterase inhibitor (ChEI) drugs taken for dementia and Alzheimer's disease. The research was based on the dissertation work of the study's first author Prajakta Masurkar. 

29 jan 2022--Dementia is a group of symptoms associated with a decline in memory, reasoning or other thinking skills. Alzheimer's disease is the most common cause of dementia, accounting for 60%–80% of cases. ChEI drugs, including donepezil, galantamine and rivastigmine increase communication between nerve cells to enhance cognition.  

"The study found that the risk of overactive bladder varies across individual ChEIs," reports Rajender R. Aparasu, Mustafa and Sanober Lokhandwala Endowed Professor of Pharmacy and chair, Department of Pharmaceutical Health Outcomes and Policy. "Using a national cohort of older adults with dementia, we also found that donepezil was associated with a 13% increased risk of OAB compared to rivastigmine, whereas there was no differential risk of OAB with galantamine and rivastigmine." 

Using Medicare data, the study examined 524,975 adults (aged 65 and older) with dementia who were users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics, drugs that help correct overactive bladder, within six months of ChEI initiation. 

While some studies have been conducted to evaluate the effects of all ChEIs and antimuscarinic use, few studies have been conducted regarding the effects of individual ChEIs on the risk of OAB. Previous studies have found that the use of ChEIs is associated with an increased risk of receiving an antimuscarinic drug.  

This study opens a new door. 

"The findings suggest the need to understand and manage medication-related morbidity in older adults with dementia," said Aparasu.

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More information: Prajakta P. Masurkar et al, Risk of overactive bladder associated with cholinesterase inhibitors in dementia, Journal of the American Geriatrics Society (2021). DOI: 10.1111/jgs.17579

 

Grapes increase gut biome diversity and lower cholesterol

by Bob Yirka , Medical Xpress

Credit: Pixabay/CC0 Public Domain

A team of researchers at the University of California's, David Geffen School of Medicine, has found evidence showing that eating grapes can increase gut biome diversity and also lower cholesterol levels in the blood. In their paper published in the journal Nutrients, the group describes experiments in which they fed volunteers grape powder for four weeks.

29 jan 2022--Prior research has shown that eating certain fruit, such as apples and grapes, can promote healthy blood vessels because they contain polyphenols, which are antioxidants. Eating such fruits also lowers blood sugar and blood pressure levels. And in some cases, polyphenol consumption has been shown to reduce inflammation, a contributing factor in heart disease. In this new effort, the researchers looked at other possible health benefits of eating grapes.

To learn more about possible positive health benefits, the group enlisted the assistance of 19 healthy adults. Each ate a special diet low in polyphenols and fiber for four weeks. Then, each subject ate the same diet but with the addition of grape powder. The volunteers ate 46 grams of the powder each day, which is equivalent to two servings of grapes. The researchers collected stool, blood and urine samples from the volunteers during both stages of the experiment.

They found that after four weeks of eating the grape powder, all of the volunteers saw increases in gut biome diversity. Prior research has shown that increased gut biome diversity tends to be associated with a strong immune system. Notably, levels of Akkermansia bacteria, which is known to have a positive impact on glucose levels and lipid metabolism, increased. The researchers also found a decrease in overall cholesterol levels of 6.1 percent and a 5.9 percent drop in LDL. And they also found some steroid acids in bile dropped by 40.9 percent—prior research has shown they play a role in cholesterol metabolism.

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More information: Jieping Yang et al, Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study, Nutrients (2021). DOI: 10.3390/nu13113965

 

New neural circuits that regulate spatial learning and memory in the brain's hippocampal formation discovered

by University of California, Irvine

Schematic summary of new hippocampal circuit connections that are revealed in the new PLOS Biology study. The illustration of spatial topology of non-canonical inputs to dorsal hippocampal CA3 (top), and the diagram of differential input strengths and patterns to the dorsal CA3 subregions (bottom) are shown. Credit: UCI School of Medicine

A research team led by University of California, Irvine has discovered new neural circuits that regulate spatial learning and memory in the brain's hippocampal formation. The team identified novel functional roles of new circuit connections between the venal CA1 region and dorsal CA3 regions of the hippocampus and demonstrated that genetic inactivation of this projection impairs object-related spatial learning and memory, but does not modulate anxiety-related behaviors.

29  jan 2022--The study, titled "Non-canonical projections to the hippocampal CA3 regulate spatial learning and memory by modulating the feedforward hippocampal trisynaptic pathway," was published today in PLOS Biology.

The hippocampus is not a homogenous brain area. The septotemporal axis, along which the trisynaptic pathway is located, separates the dorsal region of the hippocampus, which is more involved in learning, memory and spatial navigation, and the ventral region, which plays a role in emotional behavior. The trisynaptic's feedforward, unidirectional circuit organization is well documented, but the connectivity across septal to temporal regions is less well described.

"Our findings extend the knowledge of hippocampal connectivity and its relation to learning and memory processes across the septotemporal axis and provide a circuit foundation to explore these novel functional roles," said Xiangmin Xu, Ph.D., Chancellor's Fellow and professor of anatomy and neurobiology, and director for the Center for Neural Circuit Mapping (CNCM) at the UCI School of Medicine. "The new hippocampal circuit mechanism is highly relevant to treating learning and memory disorders, including Alzheimer's disease."

Building on their earlier work, Xu and his team used multiple viral tracers, including monosynaptic rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new hippocampal CA1 projections to CA3. Robust mapping results showed that CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. They also found that genetic inactivation of the CA1 to CA3 projection impaired object-related spatial learning and memory, but did not modulate anxiety-related behaviors.

"The emergence of viral-genetic mapping techniques enhances our ability to determine the detailed complexity of brain circuity," Xu said. "Our study was made possible by the new viral genetic tools developed by our CNCM investigators at UCI. We are developing these new viral tracers as brain mapping tools, which we plan to share through our center for use by the neuroscience community."

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More information: Xiaoxiao Lin et al, Noncanonical projections to the hippocampal CA3 regulate spatial learning and memory by modulating the feedforward hippocampal trisynaptic pathway, PLOS Biology (2021). DOI: 10.1371/journal.pbio.3001127

Yanjun Sun et al, CA1-projecting subiculum neurons facilitate object–place learning, Nature Neuroscience (2019). DOI: 10.1038/s41593-019-0496-y

 

Why do we forget? New theory proposes 'forgetting' is actually a form of learning

by Thomas Deane, Trinity College Dublin

The new theory proposes that forgetting is due to circuit remodelling that switches engram cells from an accessible to an inaccessible state. Credit: Dr. Nora Raschle

We create countless memories as we live our lives but many of these we forget. Why?

29 jan 2022--Counter to the general assumption that memories simply decay with time, 'forgetting' might not be a bad thing—that is according to scientists who believe it may represent a form of learning.

The scientists behind the new theory—outlined today in the international journal Nature Reviews Neuroscience—suggest that changes in our ability to access specific memories are based on environmental feedback and predictability. Rather than being a bug, forgetting may be a functional feature of the brain, allowing it to interact dynamically with the environment.

In a changing world like the one we and many other organisms live in, forgetting some memories can be beneficial as this can lead to more flexible behavior and better decision-making. If memories were gained in circumstances that are not wholly relevant to the current environment, forgetting them can be a positive change that improves our wellbeing.

So, in effect, the scientists believe we learn to forget some memories while retaining others that are important.

Forgetting of course comes at the cost of lost information, but a growing body of research indicates that, at least in some cases, forgetting is due to altered memory access rather than memory loss.

The new theory has been proposed by Dr. Tomás Ryan, Associate Professor in the School of Biochemistry and Immunology and the Trinity College Institute of Neuroscience at Trinity College Dublin, and Dr. Paul Frankland, Professor in the Department of Psychology at the University of Toronto and the Hospital for Sick Children in Toronto.

Both Dr. Ryan and Dr. Frankland are fellows of the Canadian global research organization CIFAR, which enabled this collaboration through its Child & Brain Development program, which is pursuing interdisciplinary work in this area.

Dr. Ryan, whose research team is based in the Trinity Biomedical Sciences Institute (TBSI), said:

"Memories are stored in ensembles of neurons called 'engram cells' and successful recall of these memories involves the reactivation of these ensembles. The logical extension of this is that forgetting occurs when engram cells cannot be reactivated. The memories themselves are still there, but if the specific ensembles cannot be activated they can't be recalled. It's as if the memories are stored in a safe but you can't remember the code to unlock it.

"Our new theory proposes that forgetting is due to circuit remodeling that switches engram cells from an accessible to an inaccessible state. Because the rate of forgetting is impacted by environmental conditions, we propose that forgetting is actually a form of learning that alters memory accessibility in line with the environment and how predictable it is."

Dr. Frankland added:

"There are multiple ways in which our brains forget, but all of them act to make the engram—the physical embodiment of a memory—harder to access."

Speaking to the case of pathological forgetting in disease, Dr. Ryan and Dr. Frankland note:

"Importantly, we believe that this 'natural forgetting' is reversible in certain circumstances, and that in disease states—such as in people living with Alzheimer's disease for example—these natural forgetting mechanisms are hijacked, which results in greatly reduced engram cell accessibility and pathological memory loss."

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More information: Tomás J. Ryan et al, Forgetting as a form of adaptive engram cell plasticity, Nature Reviews Neuroscience (2022). DOI: 10.1038/s41583-021-00548-3

 

Heart disease causes early brain dysfunction and can triple key Alzheimer's protein

by University of Sheffield

Credit: Unsplash/CC0 Public Domain

Heart disease can directly cause brain dysfunction early on which could lead to dementia and can triple the amount of an Alzheimer's protein in the brain, say scientists.

29 jan 20222--The new research, published in eLife, has found that heart disease causes a breakdown of a key brain function which links brain activity and blood flow, meaning the brain gets less blood for the same amount of activity.

This is happening in heart disease patients before the build up of fat in the brain's blood vessels (atherosclerosis) and is a prelude to dementia. Until now it has been unclear how some forms of vascular dementia can happen years before atherosclerosis in the brain.

The researchers also discovered that the combination of heart disease and a genetic predisposition for Alzheimer's Disease trebles the amount of beta-amyloid, a protein that builds up and triggers Alzheimer's, and increases the levels of an inflammatory gene (IL1) in the brain.

Dr. Osman Shabir, lead author of the study from the University of Sheffield's Neuroscience and Healthy Lifespan Institutes, says that "Alzheimer's Disease is the most common form of dementia worldwide and heart disease is a major risk factor for both Alzheimer's and dementia. The new findings are key to furthering our understanding of the links between heart disease and dementia."

"We've discovered that heart disease in midlife causes the breakdown of neurovascular coupling, an important mechanism in our brains which controls the amount of blood supplied to our neurons. This breakdown means the brain doesn't get enough oxygen when needed and in time this can lead to dementia."

The team have since been awarded a three year grant by the British Heart Foundation to look at the use of an arthritis drug which targets IL1 to see if it could reverse or reduce the brain dysfunction seen to be caused by heart disease.

The team also found that brain injuries can also worsen brain blood flow regulation, supporting observations that patients' symptoms often worsen after injuries or falls.

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More information: Osman Shabir et al, Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer's disease, eLife (2022). DOI: 10.7554/eLife.68242

 

Intervention leads to increase in primary care screenings for older adults

by Regenstrief Institute

Credit: CC0 Public Domain

Falls and dementia are some of the most common syndromes affecting the health of older adults, but many primary care physicians are not specifically trained to screen for them. The Indiana Geriatrics Education and Training Center (Indiana GETC) created a successful intervention combining education and workflow that increased primary care screenings for these geriatric conditions. 

29 jan 2022--"There is a shortage of geriatrics specialists, so most older adults receive care from a primary care provider. That's why it is so important to integrate geriatrics into primary care," said lead study author Debra Litzelman, M.D., M.A., research scientist at Regenstrief Institute and the principal investigator and director of Indiana GETC.  "We created an intervention that improves attitudes toward older adults and leverages teamwork to integrate these important screenings into care delivery. This study demonstrates that this intervention can be successfully implemented in primary care settings."

The Indiana GETC delivered an interdisciplinary education course for primary care providers and staff including medical assistants, nurses, and social workers about older adults' specific health concerns and screenings. They also created an electronic health record (EHR) flow sheet with screening questions that would be automatically triggered for office visits of patients 65 years or older. Each survey was only two questions and delivered by medical assistants as the patient was being taken to the exam room. Results were then communicated to the primary care provider. 

The intervention was rolled out at eight Federally Qualified Health Centers in a health system in Indianapolis. More than 6,600 geriatric patients were cared for during the course of this study. Populations served were 51 percent Black and 33 percent Caucasian. 

The study team found that after the education sessions, provider attitudes toward older patients and perceptions of the importance of a team approach to care became significantly more positive. 

Screening rates also increased during training, and continuously increased afterward. This has happened at all sites for both dementia and falls surveys. 

"The greater understanding of the needs of older adults provided by the education sessions likely primed the care teams to implement changes related to screenings," said Dr. Litzelman. "The fact the screeners did not disrupt the patient flow was also a key to success. This intervention is actively being shared with other national Geriatrics Workforce Enhancement Programs."

"Combined interprofessional education and system intervention to improve screening older adults for dementia and falls" is published in Gerontology & Geriatrics Education online ahead of print. 

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More information: Debra K. Litzelman et al, Combined interprofessional education and system intervention to improve screening older adults for dementia and falls, Gerontology & Geriatrics Education (2021). DOI: 10.1080/02701960.2021.2001336

 

For people over 50, even 'mild' COVID‑19 can result in mobility problems

by Alison Auld, Dalhousie University

Researchers surveyed more than 24,000 people over the age of 50 from across Canada during the initial phase of the lockdown in 2020 to determine the effect of a COVID diagnosis on their mobility. Credit: Timon Studler photo/Unsplash

Adults over age 50 who experience mild or moderate COVID-19 are at greater risk of worsening mobility and physical function even if hospitalization is not required to treat the virus, according to new research out of Dalhousie and other Canadian universities.

29 jan 2022--The findings, which used data from the Canadian Longitudinal Study on Aging (CLSA), highlight the burden of COVID-19 among middle-aged and older adults who are not hospitalized, and suggest that many patients who experience even mild COVID-19 have persistent and troublesome symptoms.

Researchers surveyed more than 24,000 people over the age of 50 from across Canada during the initial phase of the lockdown in 2020 to determine the effect of a COVID diagnosis on their mobility. Their findings were published Wednesday in the journal JAMA Network Open.

The team looked at mobility issues including difficulty getting up from sitting in a chair, ability to walk up and down stairs without assistance and walking two to three neighborhood blocks, as well as changes in participants' ability to move around the home, engage in housework and physical activity.

Susan Kirkland (shown left), a Dalhousie research professor and head of the school's Department of Community Health and Epidemiology, co-authored the paper that is believed to be one of the first to evaluate the association between mobility and COVID-19 in older adults.

"We found that even those with mild and moderate illness due to COVID-19 experienced adverse changes in mobility and physical function compared to individuals without COVID-19," says Dr. Kirkland.

"These findings are worth noting because they indicate that the negative effects of COVID-19 are much broader and impact a wider range of older adults than those who are hospitalized for COVID-19."

Double the odds

Participants with COVID-19 had nearly double the odds of worsening mobility and physical function compared to those without COVID-19, although most had mild or moderate symptoms. Of the 2,748 individuals with confirmed, probable or suspected COVID-19, 94 percent were not hospitalized.

Individuals with confirmed or probable COVID-19 had double the odds of worsening ability to engage in household activities and participate in physical activity than those without COVID-19. Similar results were found for those with suspected COVID-19.

"Our results showed there was a higher risk for mobility problems in people who were older, had lower income, those with three or more chronic conditions, low physical activity and poorer nutrition," says Marla Beauchamp, an assistant professor in the School of Rehabilitation Science at McMaster.

"However, those factors alone did not account for the mobility problems we observed among people with COVID-19. Rehabilitation strategies need to be developed for adults who avoid hospitalization due to COVID-19 but still need support to restore their mobility and physical function."

The researchers concluded that there is a need to further understand the long-term impacts of COVID-19 and consider "the development and implementation of effective intervention and management approaches to address any persistent deficits in mobility and functioning among those living in the community."

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More information: Marla K. Beauchamp et al, Assessment of Functional Mobility After COVID-19 in Adults Aged 50 Years or Older in the Canadian Longitudinal Study on Aging, JAMA Network Open (2022). DOI: 10.1001/jamanetworkopen.2021.46168

 

Ozone exposure linked to cognitive decline in older adults

by Colin Poitras, Matthew Kristofferson, Yale University

Graphical abstract. Credit: DOI: 10.1016/j.envint.2021.107072

A new, large-scale study led by scientists at the Yale School of Public Health has established a robust link between long-term ozone exposure and an increased risk of cognitive impairment in older adults.

29 jan 2022--Air pollution has long been considered a major risk factor for an aging society. Fine particulate matter floating in increasingly high concentrations around the globe can lead to dementia and other cognitive disabilities, and those affected can easily burden health care systems in areas with populations that skew older. But beyond airborne particles, little is known about the way in which other pollutants can pose a similar danger.

For their study, which was published in Environment International in January 2022, the researchers instead chose to focus on ambient ozone, a highly reactive gas that exists in much of smog at ground level. They then observed health outcomes in nearly 10,000 older adults across China and analyzed the extent to which long-term ozone exposure may have impacted their cognitive ability over time.

The results, they found, were startling. For every 10 microgram increase of yearly average ozone exposure, the risk for cognitive impairment grew by more than 10%. Through their analysis, the researchers also found that this association held even when they abstracted away individual risk factors such as smoking, drinking and education level. That is, older adults in China who were exposed to high levels of yearly ozone pollution were more likely to develop cognitive disabilities later in life, no matter what other activities they were involved in.

"Our findings suggest potential benefits in delaying the progression of cognitive decline among older adults if ozone levels are reduced below the new WHO Global Air Quality Guideline for ozone pollution," said Kai Chen, Ph.D., assistant professor at the Yale School of Public Health and the study's lead author.

There are limitations to their findings, however. The Yale-led team of researchers noted in their paper that the observational data alone are insufficient to establish a causal link between ozone and cognitive decline in older adults. More studies are needed to explore the mechanisms behind ozone's destructive capabilities in humans before such a claim can be made, they wrote. And since many older adults in China spend most of their time inside, indoor levels of ozone pollution could be different from the open-air averages the researchers used in their study.

Nonetheless, the study is the first to establish this link across large swaths of the Chinese population over several years. And they match what other researchers have found in areas across the globe: Over the past several years, studies have traced a similar link in adults in the United States and in Taiwan, and have also found an association between ozone exposure and other neurological diseases.

The results point to an urgent need to curtail ozone exposure across the globe, they wrote in their study, in an effort to keep healthcare systems from being overwhelmed as pollution rises and the world population gets older.

YSPH Professor Robert Dubrow, M.D., Ph.D., faculty director at the Yale Center on Climate Change and Health and a co-author of the study, said what makes this issue more urgent is that "ozone pollution is projected to be worsening under climate change." Strategies to reduce this threat, Dubrow said, "may help maintain a higher quality of life among older adults and bring significant public health benefits to an aging society."

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More information: Qi Gao et al, Long-term ozone exposure and cognitive impairment among Chinese older adults: A cohort study, Environment International (2022). DOI: 10.1016/j.envint.2021.107072

 

Telemedicine may increase surgical care for historically underrepresented patient groups

by Brigham and Women's Hospital

Credit: Unsplash/CC0 Public Domain

The COVID-19 pandemic transformed the way that patients access health care. While previous studies have revealed inequities in telemedicine usage during the spring of 2020, there are fewer analyses of other aspects of its use during the pandemic, especially among surgical patients. Researchers at Brigham and Women's Hospital analyzed the electronic health records of new patients seeking consultations within the hospital's Division of General and Gastrointestinal Surgery from March through December 2020. Their findings, published in the Journal of the American College of Surgeons, reveal increased use of telemedicine among some historically underrepresented patient groups and may inform future efforts to improve telemedicine access.

29 jan 2022--"We can use digital health to reach populations that have historically not had optimal access to our health care system," said corresponding author Gezzer Ortega, MD, MPH, of the Brigham's Center for Surgery and Public Health. "In the past decade, smart-phone usage has greatly increased in the United States. We are doing our best to meet patients where they are, and digital tools may help us bridge that gap, if we use them responsibly."

The study included two phases, one of which spanned the Massachuetts Public Health Emergency (March 24 to June 23, 2020), when the state issued a stay-at-home advisory and elective surgeries were suspended. During this period, the Brigham developed initiatives to increase telemedicine access. These included enrolling patients from under-resourced communities in the patient portal system, disseminating internet-enabled devices, and integrating a video conferencing platform into the electronic health record. During Phase 2 of the study (June 24 to December 31, 2020), Massachusetts issued reopening guidelines authorizing the resumption of non-essential elective surgeries.

Notably, in Phase 2 of the study, Black patients utilized telemedicine more than white patients even as in-person consultations increased. Hispanic/Latinx patients had audio-only consultations more than other ethnic groups during Phase I of the study, but not Phase 2, which could reflect improvements in digital access or literacy. Still, disparities in video-use persisted, with older patients, patients with lower education levels, and patients with a primary language other than English less likely to use video during virtual visits in Phase 2. Throughout the study, women were more likely to use telemedicine than men.

The study authors note that their findings only reflect telemedicine use within one surgical division. During the COVID-19 pandemic, many populations have been unwilling or unable to seek medical care, and are therefore left out of research studies. Furthermore, the demographics of the hospital's patient population, which are similar to Massachusetts demographics, limit the generalizability of these results, and additional studies are required within populations that have a larger proportion of racial and ethnic minorities, uninsured patients and non-English speakers.

Going forward, the researchers hope to continue to promote telemedicine access by reducing language barriers embedded in digital health platforms, providing better resources to help patients navigate these platforms, and improving physicians' comfort with digital systems, especially under circumstances in which patients may have audio-only access.

"There is a digital divide in the United States, with disparities in access to technology among under-resourced populations, racial and ethnic miniorities, and the elderly, among others," said Ortega. "The COVID-19 pandemic pushed digital technology upon us, whether we wanted to use it or not. The learning curve was steep, but I think we're at a point where this technology has been adopted and is part of our armamentarium of resources that we can use to care for our patients. In doing so, we need to optimize these technologies so that they can be delivered equitably."

More information: Eruchalu, Chukwuma N et al, Demographic Disparity in Use of Telemedicine for Ambulatory General Surgical Consultation During the COVID-19 Pandemic: Analysis of the Initial Public Health Emergency and Second Phase Periods, Journal of the American College of Surgeons (2022). DOI: 10.1097/XCS.0000000000000030

 

Hospital attendance not associated with increased risk of COVID transmission

by King's College London

Credit: CC0 Public Domain

These results follow from an analysis of asymptomatic, positive COVID-19 cases in cancer patients during the outbreak of the alpha variant, between December 2020 and February 2021.

29 jan 2022--The new study, led by Professor Mieke Van Hemelrijck of the School of Cancer & Pharmaceutical Sciences, analyzed data from cancer patients who were attending Guy's and St Thomas' NHS Foundation Trust.

A major driving force of the UK's second wave of COVID-19 was the evolution and spread of the alpha variant, which was associated with a greater rate of transmissibility.

A common side effect of cancer and cancer treatments is the death of immune cells, reducing the patient's ability to fight infections such as COVID-19. As a precautionary measure, treatments and follow-up care for cancer were interrupted or paused during the second wave.

To assess the risk of infection towards cancer patients, the authors analyzed COVID-19 positivity rates during the second (alpha-variant driven) wave of COVID-19.

Data were collected from 1,346 patients who tested positive with asymptomatic COVID-19 cases and a logistic regression was conducted. This statistical model was used to analyze the factors associated with COVID-19.

The results, published in Future Oncology, showed that an increased number of tests taken by asymptomatic people and living less than 20km (12.4 miles) from the epicenter of the alpha variant (the area of southeast England associated with its initial outbreak) were associated with higher positive rates.

The latter is a particularly important factor as Guy's Cancer Centre serves many patients who live in Kent and London, where the alpha variant first proliferated.

However, attending Guy's and St Thomas' NHS Foundation Trust was not associated with an increased chance in patients testing positive.

These results suggest that PPE and social distancing guidelines have so far effectively curtailed the risk of cancer patients contracting COVID-19. As a consequence, the authors support continuing cancer treatment and care for patients.

These findings will be important towards efforts to improve cancer care and treatment outcomes, as we begin to assess and manage the impact of COVID-19 related delays and disruptions.

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More information: Kathryn Tremble et al, The impact of hospital attendance on COVID-19 infection in cancer patients: an assessment of data from Guy's Cancer, Future Oncology (2022). DOI: 10.2217/fon-2021-1329

 

ACP releases two new clinical guidelines on the diagnosis and management of diverticulitis

by American College of Physicians

According to two new clinical guidelines from the American College of Physicians (ACP), uncomplicated diverticulitis can be treated in an outpatient setting without antibiotics. Patients with complicated disease should be referred for colonoscopy after an initial episode if they have not had a recent colonoscopy. Published in Annals of Internal Medicine, the guidelines are based on the best available evidence on the clinical benefits and harms, test accuracy, patient values and preferences, and consideration of costs. The clinical guidelines also include input from two public members of the organization's Clinical Guidelines Committee (CGC) and a seven-member CGC Public Panel, who provide layperson perspectives on values and preferences.

29 jan 2022--Diverticulitis is an inflammation of the diverticula, small, bulging pouches in the lining of large intestine (colon) and acute diverticulitis episodes are usually uncomplicated. Uncomplicated diverticulitis refers to localized inflammation, whereas complicated diverticulitis refers to inflammation associated with an abscess, phlegmon, fistula, obstruction, bleeding, and perforation.

In Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis, ACP suggests that clinicians:

• use abdominal CT imaging for patients when there is diagnostic uncertainty in a patient with suspected acute left-sided colonic diverticulitis;
• manage most patients with acute left-sided colonic diverticulitis in an outpatient setting;
• and initially manage select patients acute uncomplicated left-sided colonic diverticulitis without antibiotics.

In Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis, ACP suggests that clinicians:

• refer patients for a colonoscopy after an initial episode of complicated left-sided colonic diverticulitis in patients who have not had recent colonoscopy;
• do not use mesalamine to prevent recurrent diverticulitis;
• and discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either uncomplicated diverticulitis that is persistent or recurs frequently or complicated diverticulitis. The informed decision whether or not to undergo surgery should be personalized based on a discussion of potential benefits, harms, costs, and patient's preferences.

The new, evidence-based guidelines are based on systematic reviews conducted by the Brown Evidence-based Practice Center, funded by the Agency for Healthcare Research and Quality (AHRQ). The researchers extracted study data and risk of bias on the diagnosis, treatment, and management of acute left-sided diverticulitis and all studies were assessed for quality of evidence.

According to ACP, these clinical guidelines are important because diverticulitis is increasingly common in patients seen by internal medicine physicians. ACP's advice addresses the best course of treatment for patients, focused on management in an outpatient setting, with fewer drugs, to help improve a condition that can often result in quality-of-life issues and can lead to more series conditions if not treated appropriately.

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More information: Ethan M. Balk et al, Diagnostic Imaging and Medical Management of Acute Left-Sided Colonic Diverticulitis, Annals of Internal Medicine (2021). DOI: 10.7326/M21-1645

Ethan M. Balk et al, Evaluation and Management After Acute Left-Sided Colonic Diverticulitis, Annals of Internal Medicine (2022). DOI: 10.7326/M21-1646