Among the pandemic’s biggest challenges for public health experts have been just how novel it is, how hard it’s been to come by sufficient useful data, and how few tools scientists have for accurately tracking and predicting its spread.

A recent study looking at information gathered by an app that 500,000 people use to log daily symptoms, health status, and exposures to COVID-19 hints at the possible role crowdsourced big data can play in understanding and predicting the spread of infection.

The analysis looked at self-reported data from the How We Feel app collected during April and May to determine which populations were likeliest to have been tested for the virus, the prevalence of social distancing and mask wearing, and what factors were most associated with people who tested positive in that period, such as key symptoms, exposure risks, preexisting medical conditions, and demographic information.

The study showed that Black and Latinx users, frontline health care workers, and essential workers had double the risk for infection than other groups after adjusting for social-economic and preexisting medical conditions, and that those same groups, along with people who were symptomatic, were likelier than others to be tested during April and May.

According to the researchers, this was a double-edged sword, because while it meant sick people were being tested, it also meant asymptomatic cases were likely being missed due to strict testing guidelines that called for only those with symptoms to be checked. The team also found that 36 percent of app users who tested positive reported symptoms not listed by the Centers for Disease Control during the April-May timeframe, or had no symptoms at all.

“The first message from the paper is that we should provide more widespread testing beyond the vulnerable groups and symptomatic subjects,” said Harvard Professor Xihong Lin, one of the paper’s senior authors. “Those asymptomatic and mildly symptomatic cases are still infectious, so it’s important to capture those people early and to isolate them in order to avoid the spread.”

The scientists then took their results and, using novel statistical and machine learning methods, lay the foundation for models that can predict who is likely to test positive for COVID-19. The hope is that predictive models like these can soon be used to help overcome testing capacity limitations and identify disease hotspots.

Researchers found their models, which were cross-validated but need further analysis, to have about an 80 percent chance of forecasting whether an individual will test positive or negative.

The study was published in Nature Human Behavior by a team of 36 researchers from Harvard, MIT, the Broad Institute of MIT and Harvard, and a number of other institutions.

The app is the first product from the How We Feel Project, a nonprofit created from a collaboration involving Lin, professor of biostatistics at the Harvard T.H. Chan School of Public Health and professor of statistics at the Faculty of Arts and Sciences; Feng Zhang of the Broad Institute; Gary King, Albert J. Weatherhead III University Professor and director of the Institute for Quantitative Social Science; and Pinterest CEO Ben Silbermann. Others working on the project include researchers from Cornell, Stanford, University of Pennsylvania, University of Maryland School of Medicine, Howard Hughes Medical Institute, and the Bill & Melinda Gates Foundation. Teams of independent volunteers also lent their assistance.

The researchers say the idea for the study and the app, which launched in April, sprang from a need to help fill sizeable information gaps on the rampant spread of the virus in the U.S.

“Understanding the features of the COVID-19 epidemic in the U.S. by analyzing large, real data is pivotal for guiding evidence-based policies on surveillance, screening, and control measures,” Lin said. “The findings from the analysis of the How We Feel data will help achieve this goal.”

The findings argue for the importance of widespread testing, especially because of the group’s findings on asymptomatic and mildly symptomatic cases, which the researchers said were likely underestimated. Lin notes that in a recent modeling study she and another team of researchers conducted for the outbreak in Wuhan, China, they found 87 percent of cases went undetected. A recent CDC serological survey found similar results in the U.S.

Coincidentally, the results of the How We Feel study published the same week in August that the CDC modified testing guidelines to say people without symptoms didn’t need a test.

When it came to social distancing and using masks, the study found that while a substantial portion of users, 61 percent, ventured outside their homes on a daily basis from April to May the majority reported complying with guidelines on distancing and face coverings.

Some trends troubled researchers, however.

Seven percent of those who received a positive test ignored it and went to work, though the vast majority reported quarantining at home for two to seven days. Researchers also saw that 3 percent of those who tested positive for COVID-19, 10 percent who tested negative, and 13 percent who weren’t tested went to work without masks. Those who had been tested, both positive and negative, said they came into close contact with a median of one and four people respectively within three days.

“Given the evidence that mask wearing and social distancing is effective in slowing or preventing the spread of COVID-19, there was room to do better at the time in some parts of the country,” said William Allen, a junior fellow in the Harvard Society of Fellows and one of the paper’s lead authors. These numbers are likely not representative of the situation now, he said.

Along with Allen, numerous postdoctoral fellows and graduate students at Harvard, MIT, and the Broad Institute worked on the study, including co-first authors Han Altae-Tran, James Briggs, Xin Jin, Glen McGee, and Andy Shi.

Other findings from the How We Feel data showed that household and community exposure were major factors in infection. People living with someone who was infected were at 19 times the risk of testing positive themselves, and those exposed to someone in the community with the virus were at almost four times the risk. People living in high-density neighborhoods had almost double the risk of testing positive.

Forty percent of respondents who reported losing smell, taste, or both and were tested for the virus received positive results. The finding adds to growing evidence that the symptom is the greatest predictor of a positive test and that it could be used to distinguish the virus from the common flu.

While the results were provocative, the team noted the limitations of their study. Volunteers were self-selected, predominantly women (80 percent), and thus didn’t represent the general population. Also, a disproportionate number were from either Connecticut or California. How We Feel has a partnership with Connecticut, and Pinterest is based in California.

Researchers are currently focused on analyzing data from over the summer, further validating the prediction models they created, and studying data from a new emotional well-being module in the app that looks at mental health.

“[How We Feel] has continued to grow since our initial analysis,” said Zhang, the paper’s other senior author, who, with Lin, supervised all aspects of the work. “We are looking forward to sharing this rich data set with others and continuing to mine it for important insights that can help stop the spread of COVID-19.”

The delta variant of the coronavirus has been spreading rapidly throughout the U.S. and worldwide. William Hanage, associate professor of epidemiology and a faculty member of the Center for Communicable Disease Dynamics at Harvard T.H. Chan School of Public Health, discusses the threat.

In ongoing efforts to eradicate malaria, an ultrasensitive test that offers rapid, species-specific diagnostic capabilities has been developed by a research collaboration led by James Collins, a core faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering.

To achieve the goal set by the World Health Organization’s (WHO) Global Malaria Control Programme, all local transmission of malaria parasites in defined geographic areas must be eliminated. Developing tests that are useful in the low-resource settings of many areas with endemic malaria is key.

Currently, the presence of the four major malaria-causing Plasmodium species P. falciparum, P. vivax, P. ovale, and P. malariae is determined by microscopic analysis of blood samples in which parasites can be detected in red blood cells, or with so-called rapid diagnostic tests for specific Plasmodium proteins (antigens).

“Unfortunately, available rapid diagnostic approaches cannot distinguish all four Plasmodium species from one other, which can be important to initiate the definitive course of treatment,” said Nira Pollock, associate medical director of Boston Children’s Hospital’s Infectious Diseases Diagnostic Laboratory and associate professor of pathology and medicine at Harvard Medical School (HMS). “And, most importantly, they are ineffective for detecting low numbers of Plasmodium parasites in asymptomatic individuals.”

“These ‘asymptomatic carriers’ are silent reservoirs for ongoing transmission by malaria-spreading mosquitoes and extremely important for ongoing global efforts to eradicate malaria,” added Jeffrey Dvorin, associate professor of pediatrics at HMS and senior associate physician in infectious diseases at Boston Children’s Hospital.

The research team, assembled by clinical fellow Rose Lee and included Pollock and Dvorin, created a field-applicable, ultrasensitive diagnostic assay that specifically detects DNA sequences from all Plasmodium species in symptomatic and asymptomatic malaria. The new method combines an optimized 10-minute rapid sample preparation protocol with the CRISPR-based SHERLOCK system to enable highly specific and sensitive Plasmodium detection in another 60 minutes in simple reporter devices. It is published in PNAS.

Light therapy is safe and has measurable effects in the brain, according to a pioneering study by researchers from the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH). Senior investigators Rajiv Gupta, director of the Ultra-High Resolution Volume CT Lab at MGH, and Benjamin Vakoc at the Wellman Center led the study, which was supported by a grant from the Department of Defense (DOD) and published in JAMA Network Open Sept. 14.

This study is one of the first prospective, randomized, interventional clinical trials of near-infrared, low-level light therapy (LLLT) in patients who recently suffered a moderate brain injury. If further trials support these findings, light therapy could become the first widely-accepted treatment for this type of injury.

TBI is the leading cause of traumatic injury worldwide, and an estimated 69 million people experience such an injury every year. However, there are no treatments for this condition yet, largely because the underlying biological mechanisms are not well understood and it is so challenging to do studies with actual patients in the acute stage of trauma.

“The Gulf War put TBI in the headlines because body armor had been greatly improved by then,” said Gupta. “But there were still brain injuries caused by the shock waves from high powered explosives.” For a variety of reasons, the number of TBIs has increased around the globe since then, but effective treatments are still sorely needed.

For this study, a special helmet had to be designed specifically to deliver the therapy, an undertaking that required a mix of medical, engineering and physics expertise. This multidisciplinary team included Gupta, a neuroradiologist, Vakoc, an applied physicist, and others specializing in the development and translation of optical instrumentation to the clinic and biologic laboratories. Both Gupta and Vakoc are also associate professors at Harvard Medical School.

“For this study, we designed a practical, near-infrared treatment based on Wellman Center research and working directly with DOD on the vexing problem of TBI, a condition faced by so many,” said Rox Anderson, the center’s director.

Another challenge was optimizing the wavelength of the near-infrared LLLT. “Nobody knows how much light you need to get the optimal effect,” said Lynn Drake, one of the study co-authors and director of business development at the Wellman Center. “We tried to optimize the wavelength, dosing, timing of delivery, and length of exposure.” This was done through a series of pre-clinical experiments led by Anderson. These included multiple preclinical studies led by Michael Hamblin. Anderson and Hamblin are also both co-authors on this paper.

Near-infrared LLLT has already been considered for multiple uses, but to date, few if any studies of this technology have been tested and none in patients with TBI. It has been studied in stroke patients and Wellman basic laboratory research suggests it is neuroprotective through a mechanism mediated by specialized intracellular organs called mitochondria. It took several years of research at Wellman to understand the basic mechanism prior to the clinical trial.

The randomized clinical trial included 68 patients with moderate traumatic brain injury who were divided into two groups. One group received LLLT, via the special helmet, which delivered the light. Patients in the control group wore the helmet for the same amount of time, but did not receive the treatment. The helmet was designed by Vakoc’s team at Wellman. During the study, the subjects’ brains were tested for neuroreactivity using quantitative magnetic resonance imaging (MRI) metrics and the subjects also underwent neurocognitive function assessment.

MRI was performed in the acute (within 72 hours of the injury), early subacute (two to three weeks), and late subacute (approximately three months) stages of recovery. Clinical assessments were performed during each visit and at six months, using the Rivermead Post-Concussion Questionnaire, with each item assessed on a five-point scale.

New research in humans and mice identifies a particular signaling molecule that can help modify inflammation and the immune system to protect against Alzheimer’s disease. The work, which was led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH), is published in Nature.

Cognitive decline associated with Alzheimer’s disease develops when neurons begin to die. “Neuron death can be caused by improper immune responses and excessive neuroinflammation — or inflammation in the brain — triggered by high levels of amyloid beta deposits and tau tangles, two hallmarks of Alzheimer’s disease,” explains the paper’s co–senior author Filip Swirski, who conducted the work while a principal investigator in the Center for Systems Biology at MGH.

“Once neurons start dying in increasing amounts, brain cells called microglia and astrocytes — which are normally nurturing cells that clean up debris — become activated to cause neuroinflammation in an attempt to protect the brain. They are evolutionarily programmed to wipe out a brain region where there is excess neuronal cell death because it may be due to an infection, which must be stopped from spreading,” explains co–senior author Rudolph Tanzi, co-director of the McCance Center for Brain Health at MGH.

In the case of Alzheimer’s disease, the neuronal cell death, brought on by amyloid beta deposits and tau tangles, activates this response. “As neuroinflammation ensues, the amount of cell death is at least 10 times higher than that which was caused by plaques and tangles,” says Tanzi. “In fact, without the induction of neuroinflammation, there would be no symptoms of dementia. We know this from ‘resilient’ brains, in which there are lots of plaques and tangles in an individual’s brain but no symptoms at death because there was minimal or no neuroinflammation.” Tanzi provides an analogy, noting that amyloid beta is the “match” that lights the spreading “brushfires” of tangles, but only when this leads to increasing numbers of “forest fires” through neuroinflammation that is activated by microglia and astrocytes does one lose enough neurons to suffer cognitive decline and dementia.

This new study in Nature revealed that a subset of astrocytes actually tries to put out the fire by releasing a molecule called interleukin-3 (IL-3), which then converts killer microglial cells back into nurturing and protective cells that no longer wipe out neurons and instead focus on cleaning out amyloid beta deposits and tau tangles.

“There may be important clinical implications to knowing that astrocytes talk to microglia via IL-3 to educate the microglia and help them decrease the severity of Alzheimer’s disease,” says Swirski. “We can now think about how to use IL-3 to not only help curb the neuroinflammation that carries out the bulk of neuronal cell death in Alzheimer’s disease but also to entice microglia to once again take on the beneficial task of clearing away the deposits and tangles that are the initiating pathology of Alzheimer’s disease.”

“It was surprising to find IL-3 in the brain,” says first author Cameron McAlpine, then an instructor in the Center for Systems Biology. “Our findings suggest that communication between astrocytes and microglia, via IL-3, is an important mechanism that wards off Alzheimer’s disease by instructing microglia to adapt protective functions. With further study, IL-3 signaling may provide a new therapeutic opportunity to combat neurological diseases.”

Tanzi is vice chair of neurology and director of the Genetics and Aging Research Unit at MGH. Swirski is director of the Cardiovascular Research Institute and professor of medicine (cardiology) and diagnostic molecular and interventional radiology at the Icahn School of Medicine at Mount Sinai in New York City. McAlpine is assistant professor of medicine (cardiology) and neuroscience at the Icahn School of Medicine. Study co-authors include Joseph Park, Ana Griciuc, Eunhee Kim, Se Hoon Choi, PhD, Yoshiko Iwamoto, Máté G. Kiss, Kathleen A. Christie, Claudio Vinegoni, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Shun He, Henrike Janssen, Lai Ping Wong, Jeffrey Downey, Sumnima Singh, Atsushi Anzai, Florian Kahles, Mehdi Jorfi, Paolo Fumene Feruglio, Ruslan I. Sadreyev, Ralph Weissleder, Benjamin P. Kleinstiver, and Matthias Nahrendorf.

The study was funded by the Cure Alzheimer’s Fund, the National Institutes of Health, the Patricia and Scott Eston MGH Research Scholar, a Canadian Institutes of Health Research Banting Fellowship, and a Kirschstein National Research Service Award Individual Predoctoral Fellowship.

In its Three Questions, Three Answers series, Harvard T.H. Chan School of Public Health’s Laura Kubzansky discusses the link between optimism and hypertension. Kubzansky, who is co-author of the study, is the Lee Kum Kee Professor of Social and Behavioral Sciences and co-director of the School’s Lee Kum Sheung Center for Health and Happiness.

Q&A

Laura Kubzansky

Chan School: What did your study find?

Kubzansky: In a population of relatively young and healthy U.S. Army active-duty soldiers, we found that those who tested highest for optimism at the start of the study had a 22 percent lower risk of developing hypertension during three-and-a-half years of follow-up than those who scored the lowest. We know that people in the military are more susceptible to early-onset hypertension because of the stressors associated with their jobs (for example, combat exposure), so it was striking to see that much of a protective effect — and also that the finding held for both women and men, and across racial and ethnic groups.

We took into account of a lot of other factors that might have explained away the apparent effects of optimism, including number of deployments, smoking, and levels of depression, but none of them substantially altered our key finding. People who are optimistic don’t tend to be depressed, but our analysis further suggests that optimism confirms protection over and above signaling the absence of a risk factor — it’s a positive health asset.

Given that early-onset hypertension can lead to many cardiac and cardiovascular problems down the road, it’s important that we identify protective factors and seek ways to foster them early on.

Chan School: What are the pathways that might explain the health benefits of optimism?

Kubzansky: We think that optimism enhances people’s ability to regulate both their emotions and their behaviors. People who are more optimistic are less likely to smoke and to misuse alcohol, and more likely to engage in physical activity. They often have a healthier diet, although we didn’t have data on that in this particular study.

We’ve also been looking at how optimism may affect biological processes. Some research has suggested that optimism is associated with lower levels of inflammation. So, maybe there’s more anti-inflammatory activity or higher levels of antioxidants that circulate, which in turn protect against hypertension or other adverse cardiovascular outcomes. Another biological factor that we have seen in multiple studies linked to optimism is higher levels of HDL, the healthy lipids. We’re also curious to look at optimism in relation to the microbiome and are hoping to get the data to be able to do that.

One of the challenges to this work is that so much of research is focused on what causes deterioration and poor health. There are actually a lot fewer studies about what a positive biology would look like. So identifying pathways and mechanisms requires a little more creative thinking.

Chan School: Months into a global pandemic, optimism might seem like a tall order. What can people do to improve their long-term outlook?

Kubzansky: It may seem odd to talk about optimism in the midst of so much suffering. However, it’s perhaps more important than ever to think about ways to enhance functioning and not solely look at what happens when things go wrong, in the interest of preventing even more suffering later on.

With regard to optimism, the good news is that it seems to be only about 25-30 percent heritable, which means that there’s a lot of room to improve it. There’s no one-size-fits-all intervention, but there are some things that people have found can help. For example, imagining your best possible future self and the things you can do to get there. Writing a gratitude letter can also be a useful exercise, because it reminds you that good things are possible. Some people might want to try counseling or meditation as a way to find some respite from focusing just on the things that may be going wrong.

But it’s also important to talk about whether people have equal opportunity to be optimistic. For example, we’ve found that optimism tracks a lot with education. I think it’s partly because people with higher levels of education tend to pick up more problem-solving skills. So, we want to create environments where people feel like they have the power to tackle problems and be efficacious.

Our findings in the current study suggest it would be beneficial if we could find ways to improve levels of optimism relatively early in life. That’s a very grand dream, but it seems like it might be worth spending a little bit more time thinking about how to manage that. Even if you can’t fix every health problem, it may be that you can identify assets that can be made available to more people that will help them stay healthier.

A collaborative group of researchers has identified substantial microbial changes in the intestines of at-risk infants before disease onset in a new, long-term, prospective approach to the development of celiac disease. Using advanced genomic sequencing techniques, MassGeneral Hospital for Children (MGHfC) researchers, along with colleagues from institutions in Italy and the University of Maryland, College Park, uncovered distinct preclinical alterations in several species, pathways and metabolites in children who developed celiac disease compared to at-risk children who did not develop celiac disease.

As part of the MGHfC Celiac Disease, Genomic, Microbiome and Metabolomic (CDGEMM) Study, researchers identified changes in the gut microbiomes (collection of microorganisms) and metabolomes (molecular components of cells and tissues) of infants that occurred months before celiac disease onset. Changes include an “increased abundance of pro-inflammatory species and decreased abundances of protective and anti-inflammatory species at various time points preceding the onset of the disease,” according to the group’s article published in the Proceedings of the National Academy of Sciences.

“In this proof-of-concept study, we compared the gut microbiome of 10 infants who went on to develop celiac disease to the gut microbiome of 10 infants who did not develop the autoimmune condition,” says Maureen Leonard, lead author and clinical director of the Center for Celiac Research and Treatment at MGHfC. “We found significant changes in the intestinal microbes, pathways and metabolites as early as 18 months before disease onset. This was much earlier than we expected,” adds Leonard.

In CDGEMM, researchers in Italy, Spain, and the U.S. are studying 500 genetically at-risk infants from birth through age 10, allowing them to track changes in gut microbiota before celiac disease develops. CDGEMM researchers have been collecting extensive blood and fecal samples and voluminous environmental data on each participant since 2014. In this study, researchers used metagenomic analysis that enabled them to link microbial composition with function, highlighting changes in pathways associated with either increased inflammatory processes or reduced inflammation. “This study demonstrates the power of next-generation sequencing coupled with bioinformatics to detect these important changes, “says co-author Rita Colwell from the Institute of Advanced Computer Studies, University of Maryland, College Park.

“We needed a longitudinal, birth-cohort study of these at-risk infants to move microbiome research from associative observations to more causative studies,” says senior author Alessio Fasano, director of the Center for Celiac Research and Treatment at MGHfC. “This approach will help us to develop novel strategies for the diagnosis and treatment of a variety of conditions in which the microbiome could play a pathogenic role,” adds Fasano.

He suggests that these findings, if confirmed by larger datasets, may represent specific therapeutic targets for disease interception and possible prevention of celiac disease onset through microbiome manipulation during the preclinical phase. “With these findings, we anticipate that we will be able to distinguish who will remain healthy and who will develop celiac disease months before the onset of the disease,” adds Fasano.

This work was partially supported by funding from the NIH NIDDK, the Nutrition Obesity Research Center at Harvard and the Thrasher Research Fund. Colwell’s work is supported through the National Science Foundation. Italian collaborating institutions included the European Biomedical Research Institute of Salerno, various departments at the University of Salerno and University Hospital at Salerno Medical School, Sapienza University of Rome, the University of Bari, and the Center for Prevention and Diagnosis of Celiac Disease Foundation of Milan.

In a recent posting on her Facebook page, Brytney Cobia, a physician in Birmingham, Alabama, described the pain of telling COVID patients who are about to be intubated that their pleas for vaccination have come too late.

“A few days later when I call time of death, I hug their family members and I tell them the best way to honor their loved one is to go get vaccinated and encourage everyone they know to do the same,” Cobia wrote. “They thought it was a hoax. They thought it was political … They thought it was ‘just the flu.’ But they were wrong. And they wish they could go back. But they can’t.”

Testimony like Cobia’s could be key to persuading the unvaccinated to join the two-thirds of Americans who have received at least one shot, a Harvard specialist says.

An education campaign that features powerful local voices reminding people of COVID’s dangers could do more than lotteries, mandates, or a “carrots-or-stick” approach, said Robert Blendon, Richard L. Menschel Professor of Public Health and Professor of Health Policy and Political Analysis, Emeritus, Harvard T.H. Chan School of Public Health, in a Wednesday forum. The discussion was moderated by Joanne Kenen, an editor at Politico.

“The most powerful messengers are clinicians caring for very sick people who are honestly telling you that if they had had a vaccine, they wouldn’t be lying with an intubator on,” Blendon said.

COVID cases have increased in the U.S. in recent weeks, with the rise of the delta variant and a slowdown in vaccinations provoking urgent warnings from U.S. National Institute of Allergy and Infectious Diseases Director Anthony Fauci and other U.S. experts. Only 58 percent of Americans are fully vaccinated. Calls for vaccine mandates, such as President Biden’s action on federal workers, have increased, but with divides along political lines — Democrats tend to favor the measures, while Republicans tend to oppose them, polls say. A survey by Politico and the Harvard Chan School found that 64 percent of Democrats support employer mandates that require workers to be vaccinated, while 56 percent of Republicans are opposed. A similar divide exists on the question of mandated vaccinations for in-person school.

There is more consensus over health care institutions imposing vaccine mandates for workers. Seventy-four percent of Democrats and 59 percent of Republicans support such measures. This week, 60 medical organizations, including the American Medical Association, called for vaccine requirements for health care workers.

For Blendon, areas of agreement on health care mandates could represent a major step in efforts to control the pandemic and could also have an impact at the community level. Ten percent of U.S. employees work in health care. “One in 10 employees in every community in American is a very powerful next-step measure,” he said. “It has a level of political feasibility that we haven’t seen before.”

Public health messaging should be sensitive to the roots of U.S. vaccine resistance, said Blendon. Polls show that unvaccinated Americans share a deep distrust of the medical establishment, and that they are not worried about the disease. Messaging from public health experts or a barrage of general statistics about the number of cases or deaths is not going to persuade the unvaccinated, he said.

What could move the needle, in combination with health care mandates, is an education campaign in which doctors and nurses testify to the dangers of refusing vaccination. Such a campaign would ideally foreground local clinicians who can deliver a forceful message in communities across the country, said Blendon.

“It really has to be somebody who’s dealing with this every day and gets on Oklahoma TV, etc., and says, ‘Look, I am caring for people who are at risk of dying here, who thought it just wasn’t worth getting the vaccine.’

“It’s an Oklahoma critical care physician … There are no politics involved; nobody in government telling you what to do, of either party.”

Dementia is a growing problem for people as they age, but it often goes undiagnosed. Now investigators at Harvard-affiliated Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center have discovered and validated a marker of dementia that may help clinicians identify patients who have the condition or are at risk of developing it. The findings are published in JAMA Network Open.

The team recently created the Brain Age Index (BAI), a model that relies on artificial intelligence and a large set of sleep data to estimate the difference between a person’s chronological age and the biological age of their brain when computed through electrical measurements (with an electroencephalogram, or EEG) during sleep. A higher BAI signifies deviation from normal brain aging, which could reflect the presence and severity of dementia.

“The model computes the difference between a person’s chronological age and how old their brain activity during sleep ‘looks,’ to provide an indication of whether a person’s brain is aging faster than is normal,” said senior author M. Brandon Westover, investigator in the Department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. “This is an important advance, because before now it has only been possible to measure brain age using brain imaging with magnetic resonance imaging, which is much more expensive, not easy to repeat, and impossible to measure at home,” added Elissa Ye, the first author of the study and a member of Westover’s laboratory. She noted that sleep EEG tests are increasingly accessible in non-sleep laboratory environments, using inexpensive technologies such as headbands and dry EEG electrodes.

To test whether high BAI values obtained through EEG measurements may be indicative of dementia, the researchers computed values for 5,144 sleep tests in 88 individuals with dementia, 44 with mild cognitive impairment, 1,075 with cognitive symptoms but no diagnosis of impairment, and 2,336 without dementia. BAI values rose across the groups as cognitive impairment increased, and patients with dementia had an average value of about four years older than those without dementia. BAI values also correlated with neuropsychiatric scores from standard cognitive assessments conducted by clinicians before or after the sleep study.

“Because quite feasible to obtain multiple nights of EEG, even at home, we expect that measuring BAI will one day become a routine part of primary care, as important as measuring blood pressure,” said co-senior author Alice D. Lam, an investigator in the Department of Neurology at MGH. “BAI has potential as a screening tool for the presence of underlying neurodegenerative disease and monitoring of disease progression.”

Rates of childhood obesity are at historically high levels in the U.S., yet there are few interventions that promote healthy weight gain in children from infancy to age 2 — a critical period for the development and prevention of childhood obesity.

A new study published in Pediatrics found that fewer infants gained excess weight when low-income pregnant women received individualized health coaching in tandem with clinicians in community health centers and public health programs systematically changing how they delivered care to women and their infants.

“Most interventions to prevent obesity in children attempt to change the behavior of the child’s parent or family,” explains lead author Elsie Taveras, chief of the Division of General Academic Pediatrics at Massachusetts General Hospital (MGH). “But a child’s health is also influenced by how well clinical and public-health systems interact with families and provide care targeted to reducing the risk of obesity.”

The novel intervention, called the First 1,000 Days program, has the potential to have a much broader impact on childhood obesity because it reaches all women and infants.

“We can be so much more effective at preventing childhood obesity if all obstetricians pay close attention to a woman’s excess weight gain in pregnancy and if all pediatricians are trained in identifying problematic weight gain in infants, for example,” says Taveras, Conrad Taff Endowed Professor of Nutrition in the Department of Pediatrics at Harvard Medical School.

The First 1,000 Days program is also unique in combating obesity starting in the first trimester of pregnancy and in focusing on low-income families, who have the highest risk for childhood obesity.

The investigators compared infants’ weight outcomes in women and infants who received the intervention and those who received usual care. The intervention group included 995 pregnant women in their first trimester and their infants receiving care at two community health centers affiliated with Mass General Brigham. The comparison group consisted of 650 pregnant women and their infants who received usual care at two other community health centers serving low-income patients.

The intervention had two goals: to promote the adoption of healthy behavior in the women and their infants and to make systematic changes in the clinical care the women and infants received. The systems-level component of the intervention included, for example, standardizing obesity-prevention training for pediatric clinicians and staff, close tracking of infants’ weight gain, screening pregnant women for adverse health behaviors and social determinants of health, and providing educational materials and text messages to families that promoted healthy feeding and sleeping behaviors of their infants. In addition, women in the intervention group received individual support and coaching during pregnancy and the first six weeks postpartum on diet, physical activity, sleep, and stress reduction.

Infants in the intervention group had 54 percent lower odds of being overweight at six months and 40 percent lower odds of being overweight at 12 months compared with infants who received usual infant care. The researchers will continue to follow the children through age two. Mothers at the intervention sites had modestly lower, but clinically insignificant, weight retention at six weeks’ postpartum compared with mothers receiving usual care. But more women in the intervention group had a postpartum visit with a primary care clinician than the women who received usual care.

“The first six weeks after delivery are very important for positively influencing a woman’s health trajectory, so we may need a more robust intervention to achieve postpartum weight reduction,” says Taveras.

Making changes in systems of care holds the promise to improve the health of all women and their babies at community health centers and public-health programs, Taveras adds. “We believe we can create a sustained reduction in childhood obesity by moving beyond simply modifying individual behaviors and risk factors, one parent at a time.”

The next steps for the research are to find the best approaches to disseminate the intervention to other health systems that care for low-income families and to train frontline clinicians in how to implement the program for preventing childhood obesity into their practices.

Major funding for this research was provided by the Boston Foundation and the National Institutes of Health.