Bronchodilators don't improve smoking-related respiratory symptoms in people without COPD

by NIH/National Heart, Lung and Blood Institute

Credit: Pixabay/CC0 Public Domain

Researchers supported by the National Institutes of Health have found that dual bronchodilators—long-lasting inhalers that relax the airways and make it easier to breathe—do little to help people who do not have chronic obstructive pulmonary disease (COPD), but who do have respiratory symptoms and a history of smoking.

06 oct 2022--COPD, a lung disease that obstructs the airways and leads to coughing, wheezing, and shortness of breath, affects about 15 million Americans. However, millions of others who smoke or used to smoke and have some symptoms of COPD have also been prescribed bronchodilators.

"We've assumed these medications worked in patients who don't meet lung function criteria for COPD, but we never checked," said MeiLan K. Han, M.D., a principal investigator and first author of the study. "We now know these existing medications don't work for these patients."

The findings of the study, which was funded by the National Heart, Lung, and Blood Institute (NHLBI), were published in the New England Journal of Medicine and simultaneously presented at the European Respiratory Society International Congress.

According to scientists, the implications are significant. First, they show the importance of diagnosing lung conditions through spirometry, a lung function test Han noted is underutilized in clinical practice. Second, they show the need for new, effective therapies for patients without COPD.

Inhalers have long been the primary go-to treatment for these patients, she explained, because doctors either assume a patient has COPD, or if they don't, that their smoking-related symptoms could be helped by the inhalers. But while tobacco smoking causes a large spectrum of lung damage, the study showed bronchodilator therapy only helps patients with enough lung damage that would result in abnormal spirometry readings.

In the 12-week, randomized, double-blinded study, which was part of the Redefining Therapy in Early COPD for the Pulmonary Trials Cooperative (RETHINC), researchers enrolled 535 adults with symptoms of COPD, ages 40-80, at one of 20 U.S. medical centers. Twice each day, study participants used an inhaler that contained either medication or a placebo.

By the end of the trial, some adults in the medication (intervention) and placebo (control) groups saw slight respiratory improvements—this could mean they coughed less, produced less phlegm, or felt less winded—which was assessed through the St. George's Respiratory Questionnaire. However, the researchers found no significant differences between those receiving medication or placebo. They reported 56% (128 of 227) of participants who received the medication saw respiratory symptom improvements, compared to 59% (144 of 244) of those who took the placebo.

According to Han, these data underscore why we can't continue to do what we have been doing, which is not doing spirometry and just treating patients with the same COPD medications and expect that we're going to see improvement.

Antonello Punturieri, M.D., Ph.D., program director of NHLBI's Chronic Obstructive Pulmonary Disease/Environment Program, said spirometry testing should be used for any patient who shows signs of COPD, airflow obstruction, or who has a history of cigarette smoking. Though spirometry readings are used during about one-third of medical visits related to COPD, roughly half of patients who would meet criteria for COPD go undiagnosed.

Helping patients quit smoking is a primary way to prevent COPD or COPD-like symptoms, the study noted. More than 30 million adults smoke, according to the Centers for Disease Control and Prevention, and many who are not diagnosed with COPD share symptoms. About one in four current or former smokers without COPD have reported having shortness of breath. In addition to encouraging smoking cessation, doctors can help patients who do not meet lung-function criteria of COPD by working with them to address any other underlying issues, such as overweight and obesity, heart failure, or other lung issues. "In the meantime, research should be focused on finding new treatments for them," Han explained. "The next question is, can we develop more targeted therapies for these patients who are on the milder end of the spectrum?"

"Because cough and mucus production show up prominently among these patients, we believe therapies that target mucus production in the airways may be effective," said Prescott G. Woodruff, M.D., a principal investigator and senior author of the study.

---

More information: Bronchodilators in symptomatic tobacco-exposed persons with preserved spirometry for the RETHINC study group, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2204752

 

Insomnia increases likelihood of memory decline in older adults, according to new research

by Patrick Lejtenyi, Concordia University

Credit: Unsplash/CC0 Public Domain

A new Canadian study has found that older people with insomnia are at greater risk of developing memory decline and long-term cognitive impairment such as dementia.

06 oct 2022--The study, published in the journal Sleep, is based on data from more than 26,000 participants of the Canadian Longitudinal Study on Aging, all aged between 45 and 85. The researchers compared completed self-reported evaluations of sleep and memory and neuropsychological testing in several cognitive domains from 2019 and a follow-up in 2022. Participants who reported worsening sleep quality in that three-year interval also had greater odds of reporting subjective memory decline.

"We found that insomnia specifically was related to worse memory performance compared to those who have some insomnia symptoms alone or no sleep problems at all," says the study's co-lead author Nathan Cross, a postdoctoral fellow at the Sleep, Cognition and Neuroimaging Lab. "This deficit in memory was specific, as we also looked at other cognitive function domains such as attention span multi-tasking. We only found differences in memory."

Jean-Louis Zhao at the Université de Montréal was the study's co-lead. Lisa Kakinami and Thanh Dang-Vu of the PERFORM Centre contributed to the study, as did Chun Yao and Ronald Postuma from McGill University and Julie Carrier and Nadia Gosselin at UdeM.

Study flowchart and group classification for Analysis 1 and Analysis 2. NIS, no insomnia symptoms; ISO, insomnia symptoms only; PID, probable insomnia disorder. Credit: Sleep (2022). DOI: 10.1093/sleep/zsac176

Big data and a sharp focus

Unlike previous studies on sleep quality, Cross says, this one benefits from its very large data set and its focus on sleep disorders. Insomnia, he points out, has been classified as a psychological disorder in the Diagnostic and Statistical Manual of Mental Disorders, the primary reference handbook used by physicians worldwide. Insomnia is not just tossing and turning for a time before bed: "A diagnosis requires symptoms of difficulty falling asleep, staying asleep or waking too early three nights a week over a period of three months. Additionally, those with insomnia must report that this sleep problem causes them difficulty in the daytime," Cross explains.

For this study, the researchers grouped their subjects into one of three categories: those who reported no sleep problems at the 2019 baseline, those who had some insomnia symptoms and those who developed probable insomnia. When they looked at the data from 2022 follow-up, those who had reported a worsening of sleep quality—from no symptoms to some or probable insomnia, or from some symptoms to probable insomnia—were more likely to report memory decline or have it diagnosed by their physician. They were also more likely to show higher prevalence of anxiety, depression, daytime sleepiness, have breathing interruptions during sleep, other sleep-related issues, smoking and a greater body mass index (BMI) score. All of these are considered risk factors for cognitive decline and dementia. Additionally, the study found that men with insomnia perform worse on memory tests than women, suggesting that older men may be at greater risk.

"However, there is some good news: sleep disorders like insomnia can be treated," Cross adds. "This highlights the importance of properly diagnosing and managing insomnia as early as possible in older adults. Adequately treating insomnia disorder might become an important preventive measure for cognitive decline and mitigate the incidence of dementia in later life."

---

More information: Jean-Louis Zhao et al, Insomnia disorder increases the risk of subjective memory decline in middle-aged and older adults: a longitudinal analysis of the Canadian Longitudinal Study on Aging, Sleep (2022). DOI: 10.1093/sleep/zsac176

 

Older adults with regular activity routines are happier and do better on cognitive tests, study finds

by University of Pittsburgh

Credit: CC0 Public Domain

Older adults who consistently get up early and remain active throughout the day are happier and perform better on cognitive tests than those with irregular activity patterns, according to a new study led by University of Pittsburgh researchers.

06 oct 2022--The findings, published online in JAMA Psychiatry, suggest that patterns of activity—not just activity intensity—are important for healthy aging and mental health.

"There's something about getting going early, staying active all day and following the same routine each day that seems to be protecting older adults," said lead author Stephen Smagula, Ph.D., assistant professor of psychiatry and epidemiology at Pitt. "What's exciting about these findings is that activity patterns are under voluntary control, which means that making intentional changes to one's daily routine could improve health and wellness."

To learn more about daily activity patterns in U.S.-based older adults and identify links with mental health and cognition, Smagula and his team recruited 1,800 senior citizens aged over 65. Participants wore accelerometers—movement-detecting devices often found in smartphones and exercise trackers—on their wrists for seven days to measure activity, and they completed questionnaires to assess depression symptoms and cognitive function.

The analysis showed that 37.6% of participants rose early in the morning, stayed active throughout the day and had consistent daily routines.

"Many older adults had robust patterns: They get up before 7 a.m. on average, and they keep going; they stay active for 15 hours or so each day. They also tend to follow the same pattern day in, day out," said Smagula. "Lo and behold, those same adults were happier, less depressed and had better cognitive function than other participants."

Another group comprising 32.6% of participants similarly had consistent daily patterns but the participants were active for an average of just 13.4 hours each day because they rose later in the morning or settled down earlier in the evening. This group had more depression symptoms and poorer cognition than the early risers.

"People often think about activity intensity being important for health, but it might be the duration of activity that matters more," said Smagula. "This is a different way of thinking about activity: You may not need to be sprinting or running a marathon but simply staying engaged with activities throughout the day."

The remaining 29.8% of participants had disrupted activity patterns in which periods of activity were erratic throughout the day and inconsistent across days. These adults had the highest rates of depression and performed worst on cognitive tests.

According to Smagula, the relationship between mental health and activity patterns likely goes both ways: Depression or cognitive impairment can make it harder to follow a consistent routine, and conversely, having a disrupted activity rhythm may worsen these symptoms.

"Our findings suggest that activity pattern disruption is very common and associated with health problems in older adults," explained Smagula. "The relationship is likely bi-directional, so the good news is we think that simple changes—things everyone can try—can restore regular activity patterns and doing so may improve health."

Now, Smagula and his team are developing interventions to test their hypothesis that modifying behaviors to develop more consistent daily routines will boost cognition and improve mental health in older adults.

Smagula said that the first step to developing a consistent routine and getting better sleep is waking up at the same time each day—no matter how tired you are.

"The other thing is having a realistic plan to keep active through the whole day. This can be really hard—especially if you're in a slump or recovering from an injury—so it's important to be reasonable with yourself," he added. "A plan could include making a list of activities you enjoy and scheduling time to meet a friend or neighbor."

Time cues, called "zeitgebers," which help set the body's internal clock, can also assist in creating a stable routine. These include sunlight, exercise and eating. Pets, who often demand meals and walks at the same time each day, can be important social zeitgebers.

"Most people are aware of the importance of good sleep and exercise, but I think what's missing from this picture is the daily (circadian) pattern of activity," said Smagula. "Having something to wake up for each morning and having a full day that you find purposeful and rewarding might be what's important for us sleeping well at night and aging well."

More information: Stephen F. Smagula et al, Association of 24-Hour Activity Pattern Phenotypes With Depression Symptoms and Cognitive Performance in Aging, JAMA Psychiatry (2022). DOI: 10.1001/jamapsychiatry.2022.2573

 

Risk factor for developing Alzheimer's disease increases by 50-80% in older adults who have had COVID-19

by Case Western Reserve University

Credit: Pixabay/CC0 Public Domain

Older people who were infected with COVID-19 show a substantially higher risk—as much as 50% to 80% higher than a control group—of developing Alzheimer's disease within a year, according to a study of more than 6 million patients 65 and older.

06 oct 2022--In a study published today in the Journal of Alzheimer's Disease, researchers report that people 65 and older who contracted COVID-19 were more prone to developing Alzheimer's disease in the year following their COVID diagnosis. And the highest risk was observed in women at least 85 years old.

The findings showed that the risk for developing Alzheimer's disease in older people nearly doubled (0.35% to 0.68%) over a one-year period following infection with COVID. The researchers say it is unclear whether COVID-19 triggers new development of Alzheimer's disease or accelerates its emergence.

"The factors that play into the development of Alzheimer's disease have been poorly understood, but two pieces considered important are prior infections, especially viral infections, and inflammation," said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, the study's coauthor.

"Since infection with SARS-CoV-2 has been associated with central nervous system abnormalities including inflammation, we wanted to test whether, even in the short term, COVID could lead to increased diagnoses," she said.

The research team analyzed the anonymous electronic health records of 6.2 million adults 65 and older in the United States who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of Alzheimer's disease.

They then divided this population two groups: one composed of people who contracted COVID-19 during that period, and another with people who had no documented cases of COVID-19. More than 400,000 people were enrolled in the COVID study group, while 5.8 million were in the non-infected group.

"If this increase in new diagnoses of Alzheimer's disease is sustained, the wave of patients with a disease currently without a cure will be substantial, and could further strain our long-term care resources," Davis said. "Alzheimer's disease is a serious and challenging disease, and we thought we had turned some of the tide on it by reducing general risk factors such as hypertension, heart disease, obesity and a sedentary lifestyle. Now, so many people in the U.S. have had COVID and the long-term consequences of COVID are still emerging. It is important to continue to monitor the impact of this disease on future disability."

Rong Xu, the study's corresponding author, professor of Biomedical Informatics at the School of Medicine and director of the Center for AI in Drug Discovery, said the team plans to continue studying the effects of COVID-19 on Alzheimer's disease and other neurodegenerative disorders—especially which subpopulations may be more vulnerable—and the potential to repurpose FDA-approved drugs to treat COVID's long-term effects.

Previous COVID-related studies led by CWRU have found that people with dementia are twice as likely to contract COVID; those with substance abuse disorder orders are more likely to contract COVID; and that 5% of people who took Paxlovid for treatment of COVID symptoms experienced rebound infections within a month.

---

More information: Lindsey Wang et al, Association of COVID-19 with New-Onset Alzheimer's Disease, Journal of Alzheimer's Disease (2022). DOI: 10.3233/JAD-220717

 

Being lonely and unhappy accelerates aging more than smoking, study finds

by Deep Longevity

Research confirms: Psychological issues can accelerate your pace of aging. Credit: Fedor Galkin

Molecular damage accumulates and contributes to the development of aging-related frailty and serious diseases. In some people these molecular processes are more intense than in others, a condition commonly referred to as accelerated aging.

06 oct 2022--Fortunately, the increased pace of aging may be detected before its disastrous consequences manifest by using digital models of aging (aging clocks). Such models can also be used to derive anti-aging therapies on individual and population levels.

According to the latest article published in Aging-US, any anti-aging therapy needs to focus on one's mental health as much as on one's physical health. An international collaboration led by Deep Longevity with US and Chinese scientists has measured the effects of being lonely, having restless sleep, or feeling unhappy on the pace of aging and found it to be significant.

The article features a new aging clock trained and verified with blood and biometric data of 11,914 Chinese adults. This is the first aging clock to be trained exclusively on a Chinese cohort of such volume.

Aging acceleration was detected in people with a history of stroke, liver and lung diseases, smokers, and most interestingly, people in a vulnerable mental state. In fact, feeling hopeless, unhappy, and lonely was shown to increase one's biological age more than smoking. Other factors linked to aging acceleration include being single and living in a rural area (due to the low availability of medical services).

AI to connect psychological and biological aging. Credit: Fedor Galkin

The authors of the article conclude that the psychological aspect of aging should not be neglected either in research or in practical anti-aging applications. According to Manuel Faria from Stanford University, "Mental and psychosocial states are some of the most robust predictors of health outcomes—and quality of life—yet they have largely been omitted from modern health care."

Alex Zhavoronkov, the CEO of Insilico Medicine, points out that the study provides a course of action to "slow down or even reverse psychological aging on a national scale."

Earlier this year, Deep Longevity released an AI-guided mental health web service, FuturSelf.AI, that is based on a preceding publication in Aging-US. The service offers a free psychological assessment that is processed by an AI and provides a comprehensive report on a user's psychological age as well as current and future mental well-being. Deepankar Nayak, the CEO of Deep longevity affirms, "FuturSelf.AI, in combination with the study of older Chinese adults, positions Deep Longevity at the forefront of biogerontological research."

Deep Longevity developed the Longevity as a Service (LaaS) solution to integrate multiple deep biomarkers of aging dubbed "deep aging clocks" to provide a universal multifactorial measure of human biological age.

---

More information: Psychological and biological aging clocks reveal the main contributors to the aging rate in Chinese older adults, Aging-US (2022). DOI: 10.1000/xyz123

 

One in three Alzheimer's disease family caregivers has persistent symptoms of depression

by University of Eastern Finland

Credit: Pixabay/CC0 Public Domain

More than 60% of family caregivers of individuals with Alzheimer's disease (AD) experienced at least mild depressive symptoms already at the time the individual with AD was diagnosed. In one third of them, depressive symptoms worsened during a five-year follow-up.

06 oct 2022--The study carried out at the University of Eastern Finland included 226 family caregivers of individuals with AD. Depressive symptoms experienced by family caregivers were monitored for five years, starting from the diagnosis of the individual with AD. 61.5% of family caregivers experienced depressive symptoms at the time the individual with AD was diagnosed.

In more than half of them, depressive symptoms remained mild during the follow-up and even diminished in some few cases, but one third experienced an increase in depressive symptoms. In family caregivers whose depressive symptoms worsened during the follow-up, symptoms increased especially in the third and fifth year after the diagnosis of the individual with AD.

Family caregivers whose symptoms worsened were typically women caring for their spouse, and the spouse had more neuropsychiatric symptoms. However, the functional ability of the individual with AD, or the severity of their disease, were not associated with family caregivers' depressive symptoms.

Depressive symptoms weaken, for their part, family caregivers' health. So far, data on how these symptoms change over the years of giving family care, and how family caregivers differ from one another, have been scarce.

Family caregivers' health and well-being should be monitored, too

"According to this study, about one third of family caregivers experience persistent depression when giving family care. It seems that the severity or progression of the memory disorder does not explain family caregivers' symptoms, but they are rather related to individual backgrounds," says Adjunct Professor Tarja Välimäki from the Department of Nursing Science at the University of Eastern Finland.

"Family caregivers enter the caregiving situation, which often lasts many years, from different backgrounds, and these differences persist."

The results support earlier findings of the ALSOVA study suggesting that it would be possible to identify those family caregivers who accumulate several strain factors during the years of giving care. Family care also involves maintaining the health and good life of family caregivers.

"It is important to consider the health of the family caregiver already when looking into the situation of the individual with AD. Assessment and continuous monitoring of family caregivers' health and well-being should be included in the treatment of memory disorders," Välimäki says.

The study, published in Clinical Gerontologist, was carried out as part of the ALSOVA study at the University of Eastern Finland, which has conducted a five-year follow-up of individuals with a recently diagnosed AD and their family caregivers. The multidisciplinary study combines medical, therapeutic, economic, pharmacological and psychological expertise. All study participants diagnosed with AD were examined and treated in accordance with the current care guidelines for Alzheimer's disease.

---

More information: Tarja Välimäki et al, Different Trajectories of Depressive Symptoms in Alzheimer's Disease Caregivers—5-Year Follow-Up, Clinical Gerontologist (2022). DOI: 10.1080/07317115.2022.2119183

 

Super ager brains contain 'super neurons'

by Northwestern University

Credit: Pixabay/CC0 Public Domain

Neurons in an area of the brain responsible for memory (known as the entorhinal cortex) were significantly larger in super agers (80 years and older) compared to cognitively average peers, individuals with early-stage Alzheimer's disease and even individuals 20 to 30 years younger than super agers, reports a new Northwestern Medicine study.

06 oct 2022--These neurons did not harbor tau tangles, a signature hallmark of Alzheimer's disease.

"The remarkable observation that super agers showed larger neurons than their younger peers may imply that large cells were present from birth and are maintained structurally throughout their lives," said lead author Tamar Gefen, an assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. "We conclude that larger neurons are a biological signature of the SuperAging trajectory."

The study of super agers with exceptional memory was the first to show that these individuals carry a unique biological signature that comprises larger and healthier neurons in the entorhinal cortex that are relatively void of tau tangles (pathology).

The study will be published Sept. 30 in The Journal of Neuroscience.

The Northwestern Super Aging Research Program studies unique individuals known as super agers, who are 80+ year-olds who show exceptional memory at least as good as individuals 20 to 30 years their junior.

"To understand how and why people may be resistant to developing Alzheimer's disease, it is important to closely investigate the postmortem brains of super agers," Gefen said. "What makes super agers' brains unique? How can we harness their biologic traits to help elderly stave off Alzheimer's disease?"

Scientists studied the entorhinal cortex of the brain because it controls memory and is one of the first locations targeted by Alzheimer's disease. The entorhinal cortex comprises six layers of neurons packed on top of one another. Layer II, in particular, receives information from other memory centers and is a very specific and crucial hub along the brain's memory circuit.

In the study, scientists show that super agers harbor large, healthier neurons in layer II of the entorhinal cortex compared to their same-aged peers, individuals with early stages of Alzheimer's disease and even individuals 20 to 30 years younger. They also showed that these large layer II neurons were spared from the formation of tau tangles.

Taken together, the findings suggest that a neuron spared from tangle formation can maintain its structural integrity (i.e., remain healthy and large). The inverse also seems to be true: Tau tangles can lead to neuronal shrinkage.

Participants in the Super Ager study donate their brains for research.

For the study, scientists examined the brains of six super agers, seven cognitively average elderly individuals, six young individuals and five individuals with early stages of Alzheimer's. Then they measured the size of neurons in layer II of the entorhinal cortex (compared to layers III and V). They also measured the presence of tau tangles in these cases.

For reasons that remain unknown, cell populations in the entorhinal cortex are selectively vulnerable to tau tangle formation during normal aging and in early stages of Alzheimer's.

"In this study, we show that in Alzheimer's, neuronal shrinkage (atrophy) in the entorhinal cortex appears to be a characteristic marker of the disease," Gefen said.

"We suspect this process is a function of tau tangle formation in the affected cells leading to poor memory abilities in older age," Gefen said. "Identifying this contributing factor (and every contributing factor) is crucial to the early identification of Alzheimer's, monitoring its course and guiding treatment."

Future studies are needed to understand how and why neuronal integrity is preserved in super agers. Gefen wants to focus on probing the cellular environment.

"What are the chemical, metabolic or genetic features of these cells that render them resilient?" she asked. She also plans to investigate other hubs along the memory circuit of the brain to better understand the spread of or resistance to disease.

More information: Neuronal Integrity in SuperAging, The Journal of Neuroscience (2022). dx.doi.org/10.1523/JNEUROSCI.0679-22.2022