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COVID-19 infections increase risk of long-term brain problems

Researcher proposes national program to support individuals with long COVID

People who receive periodontal care have better outcomes after heart attack

Adults Show Poorer Cognition, Better Well-Being with Age

Diet could play a role in cognitive function across diverse races and ethnicities

Lifestyle medicine interventions help pediatricians manage adolescent depression




Released: September 2022


COVID-19 infections increase risk of long-term brain problems

If you've had COVID-19, it may still be messing with your brain. Those who have been infected with the virus are at increased risk of developing a range of neurological conditions in the first year after the infection, new research shows. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches, according to a comprehensive analysis of federal health data by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system.

Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson's disease.

The findings are published Sept. 22 in Nature Medicine.

"Our study provides a comprehensive assessment of the long-term neurologic consequences of COVID-19," said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. "Past studies have examined a narrower set of neurological outcomes, mostly in hospitalized patients. We evaluated 44 brain and other neurologic disorders among both nonhospitalized and hospitalized patients, including those admitted to the intensive care unit. The results show the devastating long-term effects of COVID-19. These are part and parcel of long COVID. The virus is not always as benign as some people think it is."

Overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide, Al-Aly said.

Other than having a COVID infection, specific risk factors for long-term neurological problems are scarce. "We're seeing brain problems in previously healthy individuals and those who have had mild infections," Al-Aly said. "It doesn't matter if you are young or old, female or male, or what your race is. It doesn't matter if you smoked or not, or if you had other unhealthy habits or conditions."

Few people in the study were vaccinated for COVID-19 because the vaccines were not yet widely available during the time span of the study, from March 2020 through early January 2021. The data also predates delta, omicron and other COVID variants.

A previous study in Nature Medicine led by Al-Aly found that vaccines slightly reduce -- by about 20% -- the risk of long-term brain problems. "It is definitely important to get vaccinated but also important to understand that they do not offer complete protection against these long-term neurologic disorders," Al-Aly said.

The researchers analyzed about 14 million de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation's largest integrated health-care system. Patients included all ages, races and sexes.

They created a controlled data set of 154,000 people who had tested positive for COVID-19 sometime from March 1, 2020, through Jan. 15, 2021, and who had survived the first 30 days after infection. Statistical modeling was used to compare neurological outcomes in the COVID-19 data set with two other groups of people not infected with the virus: a control group of more than 5.6 million patients who did not have COVID-19 during the same time frame; and a control group of more than 5.8 million people from March 2018 to December 31, 2019, long before the virus infected and killed millions across the globe.

The researchers examined brain health over a year-long period. Neurological conditions occurred in 7% more people with COVID-19 compared with those who had not been infected with the virus. Extrapolating this percentage based on the number of COVID-19 cases in the U.S., that translates to roughly 6.6 million people who have suffered brain impairments associated with the virus.

Memory problems -- colloquially called brain fog -- are one of the most common brain-related, long-COVID symptoms. Compared with those in the control groups, people who contracted the virus were at a 77% increased risk of developing memory problems. "These problems resolve in some people but persist in many others," Al-Aly said. "At this point, the proportion of people who get better versus those with long-lasting problems is unknown."

Interestingly, the researchers noted an increased risk of Alzheimer's disease among those infected with the virus. There were two more cases of Alzheimer's per 1,000 people with COVID-19 compared with the control groups. "It's unlikely that someone who has had COVID-19 will just get Alzheimer's out of the blue," Al-Aly said. "Alzheimer's takes years to manifest. But what we suspect is happening is that people who have a predisposition to Alzheimer's may be pushed over the edge by COVID, meaning they're on a faster track to develop the disease. It's rare but concerning."

Also compared to the control groups, people who had the virus were 50% more likely to suffer from an ischemic stroke, which strikes when a blood clot or other obstruction blocks an artery's ability to supply blood and oxygen to the brain. Ischemic strokes account for the majority of all strokes, and can lead to difficulty speaking, cognitive confusion, vision problems, the loss of feeling on one side of the body, permanent brain damage, paralysis and death.

"There have been several studies by other researchers that have shown, in mice and humans, that SARS-CoV-2 can attack the lining of the blood vessels and then then trigger a stroke or seizure," Al-Aly said. "It helps explain how someone with no risk factors could suddenly have a stroke."

Overall, compared to the uninfected, people who had COVID-19 were 80% more likely to suffer from epilepsy or seizures, 43% more likely to develop mental health disorders such as anxiety or depression, 35% more likely to experience mild to severe headaches, and 42% more likely to encounter movement disorders. The latter includes involuntary muscle contractions, tremors and other Parkinson's-like symptoms.

COVID-19 sufferers were also 30% more likely to have eye problems such as blurred vision, dryness and retinal inflammation; and they were 22% more likely to develop hearing abnormalities such as tinnitus, or ringing in the ears.

"Our study adds to this growing body of evidence by providing a comprehensive account of the neurologic consequences of COVID-19 one year after infection," Al-Aly said.

Long COVID's effects on the brain and other systems emphasize the need for governments and health systems to develop policy, and public health and prevention strategies to manage the ongoing pandemic and devise plans for a post-COVID world, Al-Aly said. "Given the colossal scale of the pandemic, meeting these challenges requires urgent and coordinated -- but, so far, absent -- global, national and regional response strategies," he said.

Story Source: Washington University in St. Louis.

Released: September 2022


Researcher proposes national program to support individuals with long COVID

While the COVID-19 pandemic wanes, the U.S. continues to face a national health challenge – the effective and equitable care of individuals with Long COVID. While the federal government is responding to this condition, few of their undertakings directly address clinical care and the potential of disability compensation. To ensure the effective and equitable care for millions of affected individuals, a Boston University School of Medicine (BUSM) researcher is urging the U.S. to commit to creating a National Long COVID Compensation Program (NLCCP).

“It will likely take years to understand the pathophysiology of this disorder, refine objective diagnostic criteria, and develop effective treatments. Many treatments will be tried, some based in biology, others offered by for-profit entities, with limited scientific basis. During this time it will be difficult for individuals to sort fact from fiction and those with financial means will pay for treatments, regardless of documented effectiveness,” says Howard C. Bauchner, MD, professor of pediatrics at BUSM.

The CDC estimates that 150 million people in the U.S. have had symptomatic COVID-19 illness. There are additional estimates that as many as 50 percent of people who have had COVID-19 still report symptoms four months following infection. If just five percent ultimately fulfill criteria for Long COVID, 7.5 million individuals would be affected in the U.S. In comparison, each year in the U.S., approximately 1.8 million individuals are diagnosed with cancer and 1.5 million with diabetes.

According to Bauchner, as more contagious variants emerge and objective diagnostic criteria for Long COVID are developed, the number of patients in need of care is expected to change. “Patients with the disease will have mild symptoms to substantial disability and it will be very difficult, particularly in individuals with diseases such as diabetes, or chronic pulmonary or cardiovascular disease, to separate the symptoms of Long COVID from those symptoms that evolve with other diseases,” he adds.

In the face of this daunting challenge, Bauchner believes that the U.S. should look to the example of the National Vaccine Injury Compensation Program, which was created in 1986 to ensure a stable supply of vaccines, protect vaccine manufactures from liability claims and fairly compensate individuals who had very rare medical consequences associated with vaccines.

“With this model in mind, I recommend that the U.S. create the NLCCP in which several entities could contribute to such a fund, including pharmaceutical and other companies that have reaped substantial profit since the pandemic began; and health and disability insurers, who would benefit from such a program,” he says.

While Bauchner admits that such a national program would face challenges, going without one may likely result in individuals not receiving the care they need, disparities in care will inevitably develop, patients will be exposed to ineffective treatments, and staggering costs will be passed on to employers and state and federal governments. “Only a coordinated, national program, could ensure an effective and equitable system of care for patients with Long COVID.”

This opinion appears online in the journal Health Affairs.

Source:  Boston University School of Medicine

Released: September 2022


People who receive periodontal care have better outcomes after heart attack

The conventional wisdom is that medical and dental care are related, but less is known about how dental care relates to health outcomes after acute incidents like heart attacks.

To that end, University of Michigan researchers studied patients receiving periodontal care, dental cleanings or no dental care during 2016-2018 and who had acute myocardial infarction (heart attack) in 2017.

They found that patients who had heart attacks and received periodontal maintenance care had the shortest length of stay in the hospital, and more follow-up visits. The longest length of stay was experienced by the no-dental-care group.

"After controlling for several factors, the periodontal care group had higher odds of having post-hospital visits," said study co-author Romesh Nalliah, associate dean for patient services at the U-M School of Dentistry. 

There was no statistically significant difference between the other groups (active periodontal care and regular care) compared to the no-care group.

The study, published in the Journal of the American Dental Association, did not establish a causal relationship between periodontal disease and heart disease, but research like this adds weight to the understanding that there is an association between oral health and overall health, Nalliah said.

There are 800,000 myocardial infarctions in the United States annually, and those with periodontal disease are at increased risk for hospitalization after a heart attack, he said.

Nalliah and colleagues wanted to examine the association between periodontal care and heart attack hospitalization, and follow-up visits in the 30 days after acute care. Using the MarketScan database, they found 2,370 patients who fit the study criteria. Of those, 47% percent received regular or other oral health care, 7% received active periodontal care (root planing and periodontal scaling) and 10% received controlled periodontal care (maintenance). More than 36% did not have oral health care before they were hospitalized after a heart attack.

"Dentistry is often practiced in isolation from overall health care," Nalliah said. "Our results add weight to the evidence that medical and dental health are closely interrelated. More and more studies like ours are showing that it is a mistake to practice medicine without the thoughtful consideration of the patient’s oral health."

Nalliah said improved communication between medical and dental teams could help with early intervention to ensure stable periodontal health in patients who have risk factors for heart disease.

"It is important to include dental care in routine medical care and this means insurances must facilitate this connection rather than offer dental insurance as a separate add-on coverage," he said.
Co-authors include Tanima Basu, senior statistician at the Michigan Hospital Medicine Safety Consortium, and Chiang-Hua Chang, research assistant professor at Michigan Medicine.
Study abstract:  Association between periodontal care and hospitalization with acute myocardial infarction

Source: University of Michigan

Released: September 2022


Adults Show Poorer Cognition, Better Well-Being with Age

The young and old could learn a thing or two from each other, at least when it comes to mental health and cognition.

In a new study, published September 12, 2022 in Psychology and Aging, researchers at University of California San Diego School of Medicine found that healthy older adults show greater mental well-being but poorer cognitive performance than younger adults. The underlying neural mechanisms may inspire new interventions to promote healthy brain function.

“We wanted to better understand the interplay between cognition and mental health across aging, and whether they rely on activation of similar or different brain areas,” said senior author Jyoti Mishra, PhD, director of the NEATLabs and associate professor of psychiatry at UC San Diego School of Medicine.

The study sampled 62 healthy younger adults in their 20s and 54 healthy older adults above age 60. Researchers evaluated participants’ mental health, surveying symptoms of anxiety, depression, loneliness and overall mental well-being. Participants also performed several cognitively demanding tasks while their brain activity was measured using electroencephalography (EEG).

The results showed significantly worse symptoms of anxiety, depression and loneliness in youth and greater mental well-being in older adults. Yet when it came to cognition, task performance was significantly lower in older adults.

EEG recordings revealed that during the tasks, older adults showed greater activity in anterior portions of the brain’s default mode network. This group of brain areas is typically active when an individual is ruminating, daydreaming or mind-wandering, and is usually suppressed during goal-oriented tasks.

“The default mode network is useful in other contexts, helping us process the past and imagine the future, but it’s distracting when you're trying to focus on the present to tackle a demanding task with speed and accuracy,” said Mishra.

While the default mode network seemed to interfere with cognition, several other brain areas appeared to improve it. Better task performance in younger adults was associated with greater activity in the dorsolateral prefrontal cortex, part of the brain’s executive control system. In the older adults, however, those with better cognitive performance instead showed greater activity in the inferior frontal cortex, an area that helps guide attention and avoid distractions.

 

The dorsolateral prefrontal cortex is known to degrade with aging, so the researchers suggest the increased inferior frontal cortex activity may be a way for older adults to compensate during these tasks.

The team is now looking into therapeutic interventions to strengthen these frontal networks, such as brain stimulation methods, while also suppressing the default mode network through mindfulness meditation or other practices that orient individuals to the present.

“These findings may provide new neurological markers to help monitor and mitigate cognitive decline in aging, while simultaneously preserving well-being,” said Mishra.

The study may also inspire new ways of addressing the mental health of younger adults. “We tend to think of people in their twenties as being at their peak cognitive performance, but it is also a very stressful time in their lives, so when it comes to mental well-being, there may be lessons to be learned from older adults and their brains,” Mishra said.

Co-authors of the study include Gillian Grennan, Pragathi Priyadharsini Balasubramani, Nasim Vahidi, Dhakshin Ramanathan and Dilip V. Jeste, all at UC San Diego.

Funding for the study came, in part, from the National Institute of Mental Health (grant T32-MH019934), the Interdisciplinary Research Fellowship in NeuroAIDS (grant R25MH081482), the Stein Institute for Research on Aging at UC San Diego, the Brain Behavior Research Fund, the Kavli Foundation, the Burroughs Wellcome Fund Career Award for Medical Scientists and the Sanford Institute for Empathy and Compassion.

Full study: https://doi.org/10.1037/pag0000710

Source: University of California San Diego

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Released: September 2022


Diet could play a role in cognitive function across diverse races and ethnicities

Dietary choices and their consequences may certainly influence cognitive function. A new study led by investigators at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, along with outside collaborators expands on previously published work (focused on Puerto Rican individuals in the U.S.) by including additional races and ethnicities. The team found that certain plasma metabolites—substances created when the body breaks down food—were associated with global cognitive function scores across the diverse set of races and ethnicities. Their results are published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
“Our study has huge strengths in expanding the sample size and in adding demographics compared to what previous research has done,” said Tamar Sofer, PhD, and director of the Biostatistics Core Program in Sleep Medicine Epidemiology and a member of the Division of Sleep and Circadian Disorders at the Brigham. “It also illustrates that studies that begin by focusing on minorities can give rise to insights that may be beneficial to other populations. We hope our findings will help people in making specific nutritional choices and in improving their cognitive health.”
Nowadays, researchers can discover biomarkers associated with health changes and diseases by utilizing approaches like metabolomic profiling, which can survey thousands of metabolites within blood samples. An initial study in Boston looking at older adults of Puerto Rican descent found a series of metabolites that were associated with measured cognitive functions. Building off that work, Brigham researchers tested metabolite-cognitive function associations in 2,222 U.S. Hispanic/Latinx adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), and in 1,365 Europeans and 478 African Americans from the Atherosclerosis Risk In Communities (ARIC) Study. They then applied Mendelian Randomization (MR) analyses to determine causal associations between the metabolites and cognitive function, as well as between a Mediterranean diet and cognitive function.
The team discovered that six metabolites were consistently associated with a lower global cognitive function across all of the studies. Four of them were sugars or derivatives of sugars. Another metabolite, beta-cryptoxanthin, was associated with a higher global cognitive function in the HCHS/SOL and is also strongly correlated with fruit consumption.  
“It is possible that these metabolites are biomarkers of a more direct relationship between diet and cognitive function,” said lead author Einat Granot?Hershkovitz, PhD, who worked on this study as a postdoctoral fellow in Sofer’s lab at the Brigham.
Diet itself can be an important source of many metabolites, including some with positive or negative associations with cognitive function. In this study, the Mediterranean diet score was associated with higher levels of beta-cryptoxanthin, which was positively associate with cognitive function. The Mediterranean diet was also negatively associated with the levels of other metabolites, which were associated with lower cognitive function. Previous research has also shown that adherence to the Mediterranean diet is associated with cognitive benefits.
While the study did have limitations like its cross-sectional, observational design which limited conclusions about the potential influence of modifying metabolite levels on cognitive function (causal inference), the researchers attempted to use MR analyses to account for unmeasured confounding and establish some level of causal inference. Their results showed weak causal effects between specific metabolites and global cognitive function. The researchers recommend that future studies assess metabolite associations with cognitive function and work to evaluate whether observed associations indeed indicate that changes in diet – manifesting in changing metabolite levels – can improve cognitive health.
“While the causal effect seen in our study may be weak, repeated research has shown that the Mediterranean diet is associated with better health outcomes, including cognitive health,” said Sofer. “Our study further supports the importance of a healthy diet towards safeguarding cognitive function, consistent across races and ethnicities.”

Paper Cited: Granot-Hershkovitz et al. “Plasma metabolites associated with cognitive function across race/ethnicities affirming the importance of healthy nutrition.” Alzheimer’s & Dementia DOI: 10.1002/alz.12786

Released: September 2022


Lifestyle medicine interventions help pediatricians manage adolescent depression

With rising prevalence of depression in adolescents, screening requirements are increasingly falling on pediatric primary care providers, who are encountering more at-risk patients. A new literature review in Harvard Review of Psychiatry underscores the evidence that non-traditional, so-called lifestyle interventions can help providers meet the growing need for youth depression management. The journal is published in the Lippincott portfolio by Wolters Kluwer.
The article reviews studies of lifestyle medicine interventions related to physical activity, sleep, nutrition, substance use, social connectedness, and stress management and provides clinical practice recommendations. “Having additional and more comprehensive details about such lifestyle recommendations could help clinicians integrate specific advice into anticipatory guidance, management, and treatment plans,” suggest Talia S. Benheim, BA, and her colleagues at Massachusetts General Hospital, along with Michelle Dalal, MD, of the University of Massachusetts Chan Medical School and Daniel Hosker, MD, in the September/October issue of the Harvard Review of Psychiatry.
Lifestyle medicine interventions can mitigate lack of access to traditional mental health treatments.
Adolescent depression is strongly associated with negative academic, employment, and health outcomes well into adulthood, and studies point to the importance of early and timely access to mental health interventions. Yet, inaccessibility of mental health services persists, especially among marginalized populations.
The utility, versatility, and cost-effectiveness of lifestyle interventions are well known. They can be used by both licensed and non-licensed providers; implemented in a standalone manner or as part of a larger treatment plan; administered in-person or virtually, with a single patient or in groups; and are often more cost-effective and accommodating to patients’ unique cultural situations.
The article reviews evidence of lifestyle interventions in physical activity, sleep, nutrition, substance use, social connectedness, and stress, demonstrating efficacy or feasibility in reducing depressive symptoms in adolescents. Studies included clinical trials, quantitative studies, and qualitative studies, as well as the authors’ own clinical experience.

Regardless of whether physical activity is considered light or rigorous, many studies demonstrate the efficacy of physical activity in reducing depression symptoms. For example, one revealed that a two-hour decrease in sedentary activity in patients between ages 12 and 16 reduced depression scores by 16%–22% by age 18.
Sleep problems in adolescents persist into adulthood and have been associated with lack of response to depressive treatment and are even a risk factor for suicide. Yet, one study demonstrated that simple and specific guidelines for healthy sleep habits improved depressive symptoms. Bedtime routines such as keeping a diary or maintaining wind-down activities, as well as cognitive-behavioral therapy for insomnia, are also important.
Nutritional studies demonstrate that healthy plant- and whole food–based diets can alleviate or reduce depressive symptoms. The authors suggest a number of simple interventional approaches, such as tip sheets or recipes, engaging professional nutritionists, and guidance on so-called mindful or intuitive eating.
Cannabis, alcohol, and nicotine are also associated with depression in adolescents and can hinder effective treatment of both. Studies show prompt intervention is paramount. An online program in Australia has shown that increased knowledge of substances, depression, and anxiety reduced likelihood of drinking.   
In adolescents, loneliness is correlated with depression, and lack of social connectedness is a predictor of suicidal ideation. One study revealed that increases in connectedness over time had corresponding reductions in adolescents’ suicidal ideation. Numerous forms of connectedness—for example, via extracurricular activities such as clubs and sports—have proven to reduce depressive symptoms and can overlap with other lifestyle interventions.
Finally, interventions to support patients in coping with and managing stress can favorably influence the onset, maintenance, and severity of depression. Successful interventions include deep breathing, meditation, muscle relaxation techniques, and mndfulness-based cognitive therapy.
The authors caution that interventions involving significant behavioral changes can be difficult, especially without social, financial, or cultural support. Despite the scarcity of randomized controlled trials of psychological and health behavior (e.g., physical activity) promoting interventions, Benheim, Dalal, and colleagues believe these interventions can help meet the increasing need for mental health services and give teens and families opportunities to empower themselves with the knowledge, skills, and habits to combat depression.
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About Harvard Review of Psychiatry
The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on a diverse range of important topics in psychiatry. Founded by the Harvard Medical School Department of Psychiatry, the journal is peer-reviewed and not industry sponsored. It is the property of President and Fellows of Harvard College and is affiliated with all of the Departments of Psychiatry at the Harvard teaching hospitals.

Articles encompass all major issues in contemporary psychiatry, including (but not limited to) neuroscience, psychopharmacology, psychotherapy, history of psychiatry, and ethics. In addition to scholarly reviews, perspectives articles, and columns, the journal includes a Clinical Challenge section that presents a case followed by discussion and debate from a panel of experts.
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