The clock, not the steam engine, is the key machine of the modern industrial age.
—Lewis Mumford, 1934

Forget long, languid summer evenings — they’re not worth the cost.

Forget the annual “spring forward,” which we curse for how tired it leaves us but welcome for the promise of warmth and light.

And, please, forget the U.S. Senate’s unanimous vote to make daylight saving time permanent. Though politicians think we want it and many of us think we’ll love it, sleep scientists assure us we won’t. It’s been tried before. The results have been disastrous, and we’ve always switched back.

In fact, researchers say, if there’s a year-round time to try, it is not daylight saving but standard time — that harbinger of winter, afternoon sunsets, and heavy coats — that should get the nod.

“They had a 50 percent chance and they chose the wrong one,” Charles Czeisler, the Frank Baldino Jr., Ph.D., Professor of Sleep Medicine at Harvard Medical School and Brigham and Women’s Hospital, said of the Senate’s vote.

Everyone knows that the shift to daylight saving in March is rough. Studies show reduced alertness and a 6 percent increase in fatal traffic accidents the following week. There is also a more lasting increase in heart attacks, strokes, and suicide, according to a 2020 position paper by the American Academy of Sleep Medicine. The shift also undoes the positive effects of changes to school start times that let high schoolers start later, after research showed they benefitted from the extra sleep.

Recent research has identified another argument for sticking with standard time year-round: cancer risk. The cancer-time connection surfaced more than a decade ago, when studies showed that night workers had higher rates of the disease, an effect disconnected from workplace carcinogens. In 2017, investigators from Harvard, Brigham and Women’s Hospital, and the National Cancer Institute revealed that rates of breast, lung, stomach, and other cancers rose among those who lived farther west across a time zone. In 2018, a research team including Harvard scientists looked specifically at the connection between time zones and liver cancer, showing a similar rise in cases the farther west a patient lived.

The exact connection between time and cancer is an area of active investigation, but Czeisler said the fact that the cancers involved are hormone-sensitive points to hormone dysregulation caused by our messed-up and misaligned schedules. A leading area of interest is melatonin.

Melatonin is “the marker of biological night,” according to Matthew Weaver, a Harvard instructor in medicine and one of the liver cancer researchers, because its levels rise and fall in a predictable 24-hour cycle. Morning light is particularly important for resetting our circadian rhythms to align with the 24-hour day. Avoiding light in the evening is also important and would become more difficult with permanent daylight saving, Weaver said, because exposure to light suppresses melatonin and delays bedtimes.

But that’s not all. Melatonin, it turns out, has anti-tumor properties, Czeisler said, making it a potential key player in the time-cancer connection.

The underlying issue, researchers say, is misalignment of three clocks. The body’s internal clock, or circadian rhythm, which is marked by rising and falling melatonin, changes in body temperature and cortisol levels, and other physiological characteristics, synchronizes each day with the rising and setting of the sun’s clock. Gumming up the works is a third clock — the social clock — which tells us when to get up, when school starts, when work starts, when to wind down for the evening, and when to close our eyes. Standard time does a decent job aligning all three clocks, while daylight saving shifts everyone an hour out of alignment.

“Daylight saving time is like living in the wrong time zone: If you’re in Boston, you go to sleep on Chicago time,” said Elizabeth Klerman, a professor of neurology at Harvard Medical School and Massachusetts General Hospital who has co-authored time-cancer research. “If you already need an alarm clock to wake up in the morning, why make it worse?”

Scientists have explored various wrinkles in our disjointed solar, biological, and social times, Klerman said. One study looked at countries whose cultures are noted for eating dinner late and found that their time zone — the social clock — was misaligned by an hour from the solar clock, offering a reason for their late-night hunger. Another study examined so-called “morning” and “evening” people, sending them on a camping expedition during which they were all exposed to the sun’s bright light all day instead of an office’s dim illumination. Everyone’s bedtime, including that of the night owls, shifted earlier.

Electric lights are part of the problem. They’re bright enough to keep us awake and make us more productive in the evenings, but they’re not bright enough to retune our body clocks. Artificial light provides somewhere between 100 and 200 lux — a measure of brightness related to a candle’s flame — but if you were to step outside even on a cloudy day, your body would be bathed in 10,000 lux or more, Czeisler said. On a clear day, you can experience 100,000 lux, a blast of light that reaches people indoors.

“We are affected by light in ways we don’t think about,” Czeisler said. “Humans like to control their environment. We live in buildings where we control the temperature. We want to be able to decide when we do things, when we sleep, when we wake. But we are not as far removed from nature as we might like to think.”

Some people compare daylight saving time with jet lag, but Czeisler said that the comparison doesn’t hold up. Jet lag’s fleeting grogginess fades as our bodies adjust to the local clock in a one-time shift. When we change the clocks to daylight saving time, our bodies are caught in misalignment between solar and social time until clocks “fall back” to standard.

If the Senate’s shift to year-round daylight saving time is approved in the House and signed by the president, we’ll be trying something that’s been tried before, expecting a different result. The move was made during World War II and again in the 1970s during an oil embargo. The consequences have included an increase in schoolchildren killed by cars from January to April, a time of the year already plagued by late sunrises.

“It’s been tried before,” Czeisler said. “People go screaming back.”

People who eat two or more servings of avocado each week may lower their risk of cardiovascular disease compared to people who rarely eat avocado, according to a new study led by researchers from Harvard T.H. Chan School of Public Health.

The researchers also found that replacing animal products such as butter, cheese, or processed meat with an equivalent amount of avocado was associated with a lower risk of cardiovascular disease events.

The study was published March 30 in the Journal of the American Heart Association.

The researchers looked at 30 years of data from more than 110,000 female and male participants in the Nurses’ Health Study and Health Professionals Follow-Up Study. After taking into account a wide range of cardiovascular risk factors and overall diet, they found that people who ate at least two weekly servings of avocado — with a serving defined as half an avocado — had a 16 percent lower risk of cardiovascular disease and a 21 percent lower risk of coronary heart disease during the study period. Those who swapped half a daily serving of animal products for avocado had a 16–22 percent lower risk of cardiovascular disease events.

Offering the suggestion to “replace certain spreads and saturated fat-containing foods, such as cheese and processed meats, with avocado is something physicians and other health care practitioners such as registered dietitians can do when they meet with patients, especially since avocado is a well-accepted food,” said lead author Lorena Pacheco, a postdoctoral research fellow in Harvard Chan School’s Department of Nutrition.

On Monday, the director of the Centers for Disease Control and Prevention, Rochelle Walensky, announced that the agency will undergo a monthlong review to evaluate potential reforms. A day later, the Harvard T. H. Chan School for Public Health convened five former leaders of the CDC to examine challenges facing the agency and provide insight on what’s to come.

After agreeing that the review is a positive step, the panelists traded ideas on priorities and solutions. One major issue is funding. Support for the agency has not been equal to the task, said Bill Foege, director from 1977 to 1983. “The resources are always so inadequate except when we have an emergency,” he said. “You think it’s going to change, but we’re always beggars.”

Julie Gerberding, director from 2002 to 2009, added that there is very little discretionary funding at the CDC; most of its money comes from line-item budgeting, which limits potential expansion.

“Emergency funds are one-time dollars,” she said. “Those monies go away as soon as the crisis is over. We don’t make sustained investments in health equity. We’re talking about public health as a cost, but we also have to think about it as an investment in health, health protection, and cost savings somewhere else in the budget.”

Tom Frieden, director from 2009 to 2017, delivered a similar message. “We have to approach our nation’s health defense with the same urgency as our military defense. We spend 300 to 500 times less on our health defense than our military defense, and yet no war in our history has killed as many people as COVID-19 has. We need sufficient funding to break the cycle of panic and neglect.”

Political controversies surrounding public health measures have affected the CDC’s messaging, the panelists noted. A restructuring could improve the relationship between the agency and leaders in the White House and Congress, though determining the nature of such changes would likely be more complicated.

Bill Roper, director from 1990 to 1993, suggested that leadership of the agency should be a term appointment confirmed by the Senate. “The Senate confirmation process is a measure of credibility put to the position,” he said. “Other counterpart agencies are all Senate-confirmed; this one should be as well.”

Gerberding and Friedman were less enthusiastic about the idea, citing the potential for politicization. Whatever the answer, ensuring that the CDC serves the mission of public health — that it remains a scientific agency, not a political one — is the ultimate goal, said Roper.

“People say, ‘We need to get the politics out of public health,’” he said. “That is never going to happen and I think that is frankly a naive notion. We need the best of science to guide decisions made by political leaders to implement effective public health programs. The issue that we face is not a scientific question; it’s our dysfunctional political system. That can’t be solved by even the wisest people that Dr. Walensky invites in.”

Rebuilding trust between the agency and the public should be a top priority, said panelists. Investing in public health goals at the state and local level could, starting with modernizing and centralizing data systems used at the agency and at health organizations across the country.

Robert Redfield, director from 2018 to 2021, recalled a briefing on the opioid crisis at which he was told that the most recent data available was three years old.

“Data modernization is a critical tool for the CDC,” he said. “We need real-time data to execute a public health response and enhance [the CDC’s] ability to be a public health response agency. We need data that comes in at a time that is actionable.”

Foege added that improving relationships among the CDC and state, local, and tribal health authorities could also help bridge the gap.

“The CDC has never had national authority over what states do in public health,” he said. “In the past, if there was an outbreak investigation, the CDC had to be asked to do that investigation, they couldn’t just go out and do it. Now, that trust has been lost and it’s trust that holds a coalition together.”

Building a cohesive, collaborative public health community not only benefits the CDC, but strengthens global health more broadly, he added.

“Anyone working on public health anywhere is working on global health,” said Foege. “We have to see ourselves as global health equity being our objective, no matter where we’re located.”

As female representation rose dramatically in U.S. medical schools, the number of Black men in academic medicine stagnated or decreased, according to a special report in the New England Journal of Medicine.

The overall picture suggests that U.S. academic medical programs must not only recruit more underrepresented clinical faculty candidates, but also find ways to support them throughout the academic pipeline to build diversity at leadership levels in medicine, says Sophia Kamran, assistant professor of radiation oncology at Harvard Medical School and a radiation oncologist at Mass General Cancer Center. Kamran led report.

Kamran’s interest in diversity in medicine stems in part from her experience as a woman of Hispanic heritage who was the first person in her family to attend college, then medical school. “I didn’t have many mentors, teachers, or role models in clinical medicine from a similar background as mine to help guide me,” says Kamran. In the NEJM report, Kamran and several colleagues assess diversity trends among U.S. medical faculty over four decades. “We wanted to see where we’ve come from, where we are, and where we need to go,” says Kamran, who led the report.

With her co-investigators, Kamran analyzed data compiled by the Association of American Medical Colleges for full-time faculty members in 18 clinical academic departments over the period from 1977 through 2019. The data represented clinical faculty, full professors, department chairs and deans. Faculty members were stratified according to sex as well as race and ethnicity. The study further stratified faculty members who were underrepresented in medicine (URM), which the AAMC defines as people who identify as Black, Hispanic, non-Hispanic Native Hawaiian or other Pacific Islander, or non-Hispanic American Indian or Alaska Native.

As they examined trends over the 42-year period, some positive news emerged. “Female representation increased dramatically,” says Kamran. For example, female clinical faculty leapt from 14.8 percent in 1977 to 43.3 percent in 2019. The proportion of female deans rose from zero to 18.3 percent.

However, while the proportion of URMs in academic medicine also rose over the study period, those increases were far more modest. As a result, Black and Hispanic women and men still represent a small part of total clinical faculty. Perhaps most worrisome, AAMC data indicate that, in general, growth and representation of Black men in academic medicine has stagnated or decreased, particularly among clinical faculty and department chairs, a trend that began about a decade ago. “This is an area in desperate need of study, because we need to reverse these trends in order to address the lack the Black leadership at all levels of academic medicine,” says Kamran.

What’s more, some URMs barely registered in the databases. At all faculty levels, non-Hispanic Native Hawaiian/other Pacific Islander and non-Hispanic American Indian/Alaska Native accounted for less than 1 percent.

Importantly, the NEJM report compared AAMC’s numbers with U.S. Census data to yield a stark finding. The proportion of women in academic medicine today has risen sufficiently over the past four decades to more closely mirror that of the population of women in this country. However, while U.S Census data also show that the country is rapidly becoming more diverse, academic medicine is not keeping pace with population change: URM representation at all levels in academic medicine is further away from reflecting the U.S. population today than it was in 2000.

Kamran’s findings concur with an earlier study by a separate group that revealed similar disparities among U.S. medical students. “The U.S. population is going to continue getting more diverse as time goes on. We’re sounding the alarm because we are clearly falling behind,” says Kamran, noting the urgency for action: Studies indicate that patients often have better health outcomes when cared for by physicians of similar backgrounds who can identify with their life experiences.

Kamran is encouraged that institutions appear to be responding to these disparities, but says it’s not enough for medical schools to set diversity quotas. “We have to also focus on retention and development,” says Kamran. “We need evidence-based initiatives that create inclusive environments that can support cultural change.”

When you think about progressive brain disorders that cause dementia, you usually think of memory problems. But sometimes language problems — also known as aphasia — are the first symptom.

What’s aphasia?

Aphasia is a disorder of language because of injury to the brain. Strokes (when a blood clot blocks off an artery and a part of the brain dies) are the most common cause, although aphasia may also be caused by traumatic brain injuries, brain tumors, encephalitis, and almost anything else that damages the brain, including neurodegenerative diseases.

How neurodegenerative diseases cause aphasia

Neurodegenerative diseases are disorders that slowly and relentlessly damage the brain. After ruling out a brain tumor with an MRI scan, you can usually tell when aphasia is from a neurodegenerative disease, rather than a stroke or other cause, by its time course: Strokes happen within seconds to minutes. Encephalitis presents over hours to days. Neurodegenerative diseases cause symptoms over months to years.

Alzheimer’s disease is the most common neurodegenerative disease, but there are other types as well, such as frontotemporal lobar degeneration. Different neurodegenerative diseases damage different parts of the brain and cause different symptoms. When a neurodegenerative disease causes problems with language first and foremost, it is called primary progressive aphasia.

How is primary progressive aphasia diagnosed?

Primary progressive aphasia is generally diagnosed by a cognitive behavioral neurologist and/or a neuropsychologist who specializes in late-life disorders. The evaluation should include a careful history of any language and other problems that are present; a neurological examination; pencil-and-paper testing of thinking, memory, and language; blood tests to rule out vitamin deficiencies, thyroid disorders, infections, and other medical problems; and an MRI scan to look for strokes, tumors, and other abnormalities that can affect the brain’s structure.

The general criteria for primary progressive aphasia include:

difficulty with language is the most prominent clinical feature at the onset and initial phases of the neurodegenerative disease
these language problems are severe enough to cause impaired day-to-day functioning
other disorders that could cause the language problems have been looked for and are not present.

There are three major variants of primary progressive aphasia

Primary progressive aphasia is divided into different variants based on which aspect of language is disrupted.

Logopenic variant primary progressive aphasia causes word-finding difficulties. Individuals with this variant have trouble finding common, everyday words such as table, chair, blue, knee, celery, and honesty. They know what these words mean, however.

Semantic variant primary progressive aphasia causes difficulty in understanding what words mean. When given the word, individuals with this variant may not understand what a table or chair is, which color is blue, where to find their knee, what celery is good for, and what honesty means.

Nonfluent/agrammatic variant primary progressive aphasia causes effortful, halting speech in which individuals know what they want to say but cannot get the words out. When they can get words out, their sentences often have incorrect grammar. Although they know what the individual words mean, they may have trouble understanding a sentence with complex grammar, such as, “The lion was eaten by the tiger.”

This is an excerpt from an article that appears on the Harvard Health Publishing website.

To read the full story

Andrew E. Budson is chief of cognitive and behavioral neurology at the Veterans Affairs Boston Healthcare System, lecturer in neurology at Harvard Medical School, and chair of the Science of Learning Innovation Group at the Harvard Medical School Academy.

A new study finds that women who had experienced infertility had a 16 percent increased risk of heart failure compared with women who did not have an infertility history.

Massachusetts General Hospital study was published in the Journal of the American College of Cardiology.

“We are beginning to recognize that a woman’s reproductive history tells a lot about her future risk of heart disease,” says first author Emily Lau, a cardiologist and director of the Menopause, Hormones & Cardiovascular Clinic at MGH. “Whether a woman has difficulty becoming pregnant, what happens during her pregnancies, when she transitions through menopause all influence her risk of heart disease later in life.”

Infertility affects about 1 in 5 U.S. women and includes a spectrum of conception difficulties, but its link with heart failure has not been well-studied until recently. Partnering with the Women’s Health Initiative (WHI), which was designed in the early 1990s and queried a woman’s reproductive history, Lau and colleagues studied postmenopausal women from the WHI and examined whether infertility was associated with development of heart failure.

There are two types of heart failure: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement related to the volume percentage of blood that is pumped from the left ventricle of the heart during each beat. An ejection fraction less than 50 percent is commonly viewed as abnormal or reduced.

The team found an association between infertility and overall heart failure, specifically with HFpEF, a form of heart failure that is far more common in women regardless of fertility history. Among the 38,528 postmenopausal women studied, 14 percent of the participants reported a history of infertility. Over a 15-year follow up period, the researchers noted that infertility was associated with 16 percent future risk of overall heart failure. When they examined heart failure subtypes, they found that infertility was associated with a 27 percent increased future risk of HFpEF.

Over the past decade, HFpEF (where the heart muscle does not relax well) as opposed to HFrEF (where the left ventricle does not pump well), has become the dominant form of heart failure in both men and women. But it remains more common in women.

“It’s a challenging condition because we still do not completely understand how HFpEF develops and we do not have very good therapies to treat HFpEF,” says Lau.

“I think our findings are particularly noteworthy because heart failure with preserved ejection fraction is more prevalent in women,” says Lau. “We don’t understand why we see HFpEF more in women. Looking back in a woman’s early reproductive life may give us some clues as to why.” Of note, the team observed that the link persisted regardless of whether an individual eventually conceived or had a live birth.

The increased risk was independent of traditional cardiovascular risk factors and other infertility-related conditions. “There has been some suggestion in previous studies that women with infertility do have more cardiometabolic risk factors,” says Lau, but the team did not find that cardiometabolic risk factors explained the link between infertility with heart failure in this study. They also looked to see if other infertility-related conditions like thyroid disease, irregular menses, and early menopause explained the association between infertility and heart failure but did not find evidence to support that hypothesis either.

“So it really begs the question: what are the mechanisms driving the association between infertility and heart failure,” says Lau. Is it shared risk factors, or is infertility on the causal pathway? She mentions vascular and endothelial dysfunction may be involved and plans on eventually clarifying the mechanism underlying the link between infertility and heart failure. In the future, Lau hopes to conduct a prospective study of women with an infertility history involving exercise parameters, vascular measures, and more, to solve the mystery.

“We as scientists and doctors are beginning to recognize how important a woman’s reproductive history is for their future risk of heart disease. Infertility is one of many cardiovascular risk factors, such as hypertension and high blood pressure, but reproductive history is not routinely considered as part of the cardiovascular risk assessment,” says Lau. Since people do not tend to develop heart failure until well in their 60s and beyond, and infertility is mostly experienced in the 20s, 30s, and 40s, many physicians are not thinking about the connection. “We cannot change a woman’s history of infertility, but if we know a woman has had a history of infertility, we can be more aggressive about counseling her about other modifiable risk factors including high blood pressure, high cholesterol, smoking, and beyond.”

Jennifer Ho was senior author on the paper. This research was supported in part by the National Institutes of Health and American Heart Association.

A team of researchers has developed a genetic risk score for six common diseases, which could assist doctors and patients when making medical decisions.

A person’s risk of developing diseases such as Type 2 diabetes or breast cancer may be influenced by thousands of genetic differences. Looking at a single DNA difference that has a small effect on risk may not be clinically useful, but when hundreds or thousands of these small risks are added up into a single score, often called a polygenic risk score (PRS), they might offer clinically meaningful information about a person’s disease risk.

In a new paper published in Nature Medicine, researchers from Brigham and Women’s Hospital, Veterans Affairs Boston Healthcare System, and Harvard Medical School developed and validated polygenic risk scores for six common diseases. The team also developed informational resources for each disease to help physicians and patients discuss how to incorporate PRS when making medical decisions about screening and prevention.

“As a primary care physician myself, I knew that busy physicians were not going to have time to take an entire course on polygenic risk scores,” said corresponding author Jason Vassy of the Brigham’s Division of General Internal Medicine & Primary Care, the Brigham’s Precision Population Health at Ariadne Labs and VA Boston. “Instead, we wanted to design a lab report and informational resources that succinctly told the doctor and patient what they need to know to make a decision about using a polygenic risk score result in their health care.”

Vassy and colleagues developed the risk scores as part of the Genomic Medicine at VA (GenoVA) Study, a randomized clinical trial of PRS testing among generally healthy adults. The study team developed and validated a laboratory test at the Mass General Brigham Laboratory for Molecular Medicine (LMM) for polygenic risk scores for atrial fibrillation, coronary artery disease, Type 2 diabetes, breast cancer, colorectal cancer, and prostate cancer.

The GenoVA Study is currently enrolling patients at the VA Boston Healthcare System, and the investigators reported the results from the first 227 patients, among whom 11 percent were found to have a high polygenic risk score for atrial fibrillation, 7 percent for coronary artery disease, 8 percent for Type 2 diabetes, and 6 percent for colorectal cancer. Among men, 15 percent had a high score for prostate cancer, while 13 percent of women had a high score for breast cancer. The GenoVA Study will ultimately enroll more than 1,000 patients and follow them for two years to observe how they and their primary care providers use the polygenic risk scores in clinical care. For example, high-risk patients might choose to undergo screening tests more frequently or take preventive medications that can lower their risk.

The researchers had to address many challenges in implementing a clinical laboratory PRS test. Most importantly, their own observations confirmed a problem that was already known about these scores: they are less accurate in individuals of non-European descent. Most genomic research to date has been conducted in European populations, thus the scores resulting from this research have a weaker ability to predict disease risk among non-European populations. Implementing a polygenic risk score into clinical care that is only accurate for people of European descent would exacerbate existing health disparities. To address this important limitation, the researchers applied additional statistical methods to enable PRS calculation across multiple racial groups.

“Researchers must continue working to increase the diversity of patients participating in genomics research,” said Matthew Lebo, chief laboratory director at the LMM. “In the meantime, we were heartened to see that we could generate and implement valid genetic scores for patients of diverse backgrounds.”

To date, 52 percent of GenoVA Study enrollees report non-white race and/or Hispanic/Latinx ethnicity.

Another key challenge in bringing polygenic risk score to clinical medicine is that physicians and patients will need support to understand them and use them to make medical decisions. Clinical guidelines do not yet exist to help a physician know whether and how they should treat a patient with a high-risk score differently than an average-risk patient, but the study provides physician- and patient-oriented educational materials to help them incorporate the results. In addition, patients and primary care physicians can seek support from a genetic counselor in the study.

The researchers hope that this first report from the GenoVA Study will be a useful guide for other laboratories and health care systems looking to implement polygenic risk score testing in patient care. “It’s still very early days for precision prevention,” says Vassy, “but we have shown it is feasible to overcome some of the first barriers to bringing polygenic risk scores into the clinic.”

Disclosures: Vassy is an employee of the U.S. Department of Veterans Affairs; the views expressed in this paper do not represent those of the VA or U.S. government.

This work was supported by the NIH National Human Genome Research Institute (R35HG010706) and the NIH (R01HL139731, R01HL157635), American Heart Association (18SFRN34250007), National Heart, Lung and Blood Institute (R01HL142711, R01HL148050, R01HL151283, R01HL127564, R01HL148565, R01HL135242, R01HL151152), National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125782), Fondation Leducq (TNE-18CVD04) and Massachusetts General Hospital (Fireman Chair).

Inside brain cells, errors in DNA can accumulate as we age. But in patients with Alzheimer’s disease, these errors — known as somatic mutations — may build up at a faster rate.

A new study by investigators from Brigham and Women’s Hospital and Boston Children’s Hospital found that patients with Alzheimer’s disease have a greater number of somatic mutations in their brain cells and that these mutations differed from people without Alzheimer’s disease. The team’s results are published in Nature.

“As we age, neurons are known to accumulate somatic mutations. In AD neurons, however, we see more mutations and DNA alterations,” said lead author Michael B. Miller of the Department of Pathology at the Brigham. “Our results suggest that AD neurons experience genomic damage that causes immense stress on cells and creates dysfunction among them. These findings may explain why many brain cells die during AD.”

The team conducted its study using single-cell whole-genome sequencing of 319 hippocampal and prefrontal cortex neurons of patients with or without AD to determine the link between the number and type of somatic mutations and AD. To better understand the genomic changes that occur in AD neurons, researchers sequenced tissue DNA and discovered a greater number of mutations termed somatic single-nucleotide variants (sSNVs) in patients with AD. Theorizing that the large number of mutations was the result of increased DNA oxidation, researchers then measured 8-Oxoguanine, an indicator of oxidative stress and DNA damage, and found that AD neurons were in fact more oxidized.

Ultimately, the discovery of accumulating DNA alterations in AD neurons provides researchers with a window into molecular and cellular events in AD pathogenesis. “Our findings suggest that the sheer number of oxidative lesions and somatic mutations we observed in AD neurons may contribute to its pathology,” said Miller.

The authors acknowledge two main study limitations. First, two groups were primarily studied: patients with no neurologic disease and those with advanced AD based on the Braak staging system. In the future, researchers are eager to study the neurons of individuals with intermediate-stage AD. Second, while single-cell, whole-genome sequencing was feasible for the preliminary studies, the authors note that there are advanced methods that allow for an in-depth analysis of each strand of DNA that should be explored in the future.

“In the future, we are eager to elucidate how the observed mutations in AD neurons cause neuronal cell death and are dedicated to aiding in the discovery of novel treatments that target these pathways,” Miller said.

Disclosures: Christopher A. Walsh is a paid consultant (cash, no equity) to Third Rock Ventures and Flagship Pioneering (cash, no equity) and is on the Clinical Advisory Board (cash and equity) of Maze Therapeutics. No research support is received. These companies did not fund and had no role in the conception or performance of this research project.

This work was supported by the National Institutes of Health (K08 AG065502,T32 HL007627, T32 GM007753, T15 LM007098, R00 AG054748, K01 AG051791, R01 NS032457-20S1, R01 AG070921, DP2 AG072437), the Brigham and Women’s Hospital Program for Interdisciplinary Neuroscience through a gift from Lawrence and Tiina Rand, the donors of the Alzheimer’s Disease Research program of the BrightFocus Foundation (A20201292F), the Doris Duke Charitable Foundation Clinical Scientist Development Award (2021183), Suh Kyungbae Foundation, the F616 Prime Foundation, and the Allen Discovery Center program, a Paul G. Allen Frontiers Group-advised program of the Paul G. Allen Family Foundation.

A recent CBS News/YouGov survey found that two-thirds of Americans want recreational marijuana use to be legal. Nearly 70 percent of states allow the medical use of cannabis products and a growing number have legalized recreational use.

But neuroscientist Yasmin Hurd says that doesn’t mean cannabis gets a clean bill of health.

What we consume as well as when in life we are exposed to it play major roles in how our brains may be affected. That was the message from Hurd, speaking in the online presentation “Neuroscience and Cannabis: Implications for Law and Policy” — which fittingly took place on 4/20, a cannabis culture allusion to marijuana.The hourlong presentation was part of the Project on Law and Applied Neuroscience, a collaboration between the Center for Law, Brain and Behavior at Massachusetts General Hospital and the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.

Hurd is the Ward-Coleman Chair of Translational Neuroscience and the director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai. She quickly reviewed the legal history of cannabis in this country, noting the huge racial disparities in arrests, convictions, and other penalties, such as the separation of mothers from their newborns following positive drug tests.

But while the biased application of law enforcement regarding marijuana has led to a trend toward legalization, the science is more unclear. Even beyond its “complex history” and “complex legal status and policies,” cannabis is a “complex plant,” said Hurd. “Cannabis contains over 500 chemicals, including over 140 cannabinoids that have a greater or lesser degree of psycho-pharmacological activity.”

And although Hurd focused primarily on cannabis’ best-known psychoactive compound — THC — and to a lesser extent CBD, she pointed out that their interaction with the human brain is complicated by another factor: the human body’s own naturally occurring cannabinoids.

Home from school and separated from peers during crucial developmental phases, young children and adolescents were clearly among the people most negatively impacted, in various ways, by the pandemic lockdowns. But early indications offer some additional, less-expected observations. Among them are that even before the outbreak hit there had been a trend of rising mental health disorders among young people and that some kids who were already wrestling with emotional issues actually seemed to do better during the pandemic.

Those insights formed part of the discussion by child psychiatric epidemiologist Tamsin Ford on Wednesday, as she addressed “The Impact of the COVID-19 Pandemic on Children’s Mental Health,” part of the Harvard T.H. Chan School of Public Health Population Mental Health Forum Series.

This crisis is still too recent for most research to be conclusive, Ford cautioned Karestan Koenen, professor of psychiatric epidemiology at the Chan School and the seminar’s host. In addition, Ford, who is affiliated with University of Cambridge, drew primarily from studies in the U.K.

A series of national surveys funded by the Department of Health in England did provide a baseline for looking at children’s mental health, however. These surveys, done in 1999, 2004, and 2017, revealed some troubling underlying trends. For example, while the physical health of children and young people up to age 24 gradually improved over this period, their mental health declined. “We were seeing a small but statistically significant increase in emotional disorders,” in particular, depression and anxiety. “And this is before we hit the pandemic,” Ford said.

What has happened since is difficult to study. A dearth of studies on children, she said, has been complicated by the problems of conducting research or large-scale surveys during a pandemic. “There’s a real issue in that we didn’t know,” she said. “All our statistical assumptions are based on having a probability sample.”