The Alzheimer’s Association has pushed relentlessly to get broad access to Aduhelm, despite safety risks and uncertain evidence that it helps patients.The day after Medicare officials announced a preliminary decision to sharply limit coverage of the controversial new Alzheimer’s medication Aduhelm, citing its unclear benefit and serious safety risks, the nation’s most prominent Alzheimer’s advocacy organization convened its policy team.The agenda: fighting Medicare’s proposal.“This is our top priority,” Robert Egge, the association’s chief public policy officer, said at the Jan. 12 session, according to recordings obtained by The New York Times.The next day, the chief executive, Harry Johns, took the mission to the entire staff, saying, “You can count on us being relentless.”Medicare’s proposal to pay for Aduhelm only for participants in randomized clinical trials was welcomed by many Alzheimer’s experts and other doctors. They say it would protect patients and families whose desperation might lead them to try anything, while also rigorously evaluating whether Aduhelm actually works.But the Alzheimer’s Association and similar groups, along with Aduhelm’s manufacturer, Biogen, strongly object. They say that Aduhelm, a monoclonal antibody that is the first drug approved for Alzheimer’s in 18 years, should be covered for anyone with mild Alzheimer’s-related cognitive decline and that usage decisions should rest with patients and their doctors.The association’s campaign makes little mention of Aduhelm’s safety risks and uncertain benefit, arguing that restricting coverage of an F.D.A.-approved drug is “shocking discrimination against everyone with Alzheimer’s disease.”With Medicare’s final decision due by April 11, the group has organized tweets directed at President Biden, emails directed at Congress, and ads on social media and websites including Univision, Essence and Martha Stewart.It has orchestrated over 400 meetings in which people with Alzheimer’s, their family members or supporters have implored their members of Congress to press the Centers for Medicare and Medicaid Services (C.M.S.) to broadly cover the drug. In sessions prepping for those meetings, association officials suggested that people say versions of phrases like “I have a fatal disease and I want more time with my family” and to discuss “how access to F.D.A.-approved treatments will impact me and my family.”Leaders also encouraged people to submit comments to C.M.S. in ways that weren’t scripted. “It is important that individuals not use our talking points,” Beth McMullen, senior director of grassroots advocacy, instructed at one meeting. Employees filing comments “cannot submit as a staff member of the Alzheimer’s Association,” she said.The push reflects growing activism by advocacy groups involved in various diseases, which sometimes campaign for therapies despite medical experts’ concerns about insufficient data. Some are partially funded by pharmaceutical companies. In fiscal year 2021, the Alzheimer’s Association received $1.6 million from manufacturers developing monoclonal antibodies, including $487,500 from Biogen.Biogen, Aduhelm’s manufacturer, gave the Alzheimer’s Association $487,500 in fiscal year 2021.C.J. Gunther/EPA, via ShutterstockOther Alzheimer’s advocacy groups are also campaigning, including UsAgainstAlzheimer’s. It has run television ads featuring patients and has written in strident language to C.M.S. that “the government would be consigning millions of Americans to inevitable decline and death, with no possibility of appeal.” The Alliance for Aging Research led a rally of about 100 people outside the Department of Health and Human Services, which houses C.M.S. (Afterward, about half the alliance’s scientific advisory board quit in opposition to the group’s position.)Understand the New Alzheimer’s Drug AduhelmF.D.A. Approval: The agency approved the first new Alzheimer’s treatment in 18 years despite fierce debate over whether it works.Potential Safety Risks: Concerns over Aduhelm intensified after a 75-year-old woman in a clinical trial developed brain swelling and died.Medicare Limits: Officials said the federal program should cover the drug only for patients who are participating in approved clinical trials.Understand Alzheimer’s: Get answers to common questions about the disease, which affects about 30 million people globally.Medicare’s coverage proposal came after Aduhelm, an expensive monthly infusion that also has the scientific name aducanumab, was approved in June by the Food and Drug Administration despite contradictory scientific results. Participants in one clinical trial appeared to experience slight slowing of cognitive decline, while patients in a nearly identical trial didn’t appear to benefit at all. About 40 percent of patients on the dosage later approved experienced brain swelling or brain bleeding, often mild, but sometimes serious. Both a council of senior F.D.A. officials and the agency’s independent advisory committee had said there wasn’t enough evidence for approval. Questions about the approval, and whether the F.D.A. worked too closely with Biogen, have prompted investigations by congressional committees, the Health and Human Services department’s inspector general, the Federal Trade Commission and the Securities and Exchange Commission. Major medical centers, including the Cleveland Clinic, have declined to offer Aduhelm.After C.M.S. announced its proposal, Dr. Lee Fleisher, the agency’s chief medical officer, said, “Our foremost goal is to protect beneficiaries from potential harm from an intervention without known benefits in the Medicare population.”The proposal has attracted extraordinary interest, with C.M.S. receiving 9,957 comments, some organized by advocacy groups on both sides of the debate.The Alzheimer’s Association, with revenue of about $400 million, is highly influential in the Alzheimer’s field: It runs an international conference, provides research grants and publishes a journal.In recordings of the staff meeting and two prep sessions, association officials didn’t mention Aduhelm’s safety risks.In an interview, Mr. Johns, the chief executive, said, “We take the safety concerns seriously,” adding, “The risks are real, but they’re not worse than treatments that are covered by Medicare today.” He proposed that patients enroll in a registry where negative effects could be reported. But many experts say that wouldn’t sufficiently evaluate the drug. At the staff meeting, Maria Carrillo, the association’s chief science officer, addressed issues of whether Aduhelm works by saying, “One of the questions that you may be asked, or maybe you’re asking yourself is: Is the scientific evidence sufficient to conclude” that Aduhelm and similar monoclonal antibodies “improve health outcomes for Medicare beneficiaries?” The answer, she said, was “yes.”While some patients enthusiastically back the association’s efforts, its stance troubles some longtime supporters of the organization, including Dr. Daniel Gibbs, a retired neurologist in Portland, Ore., with early-stage Alzheimer’s. Dr. Daniel Gibbs, a retired neurologist with early-stage Alzheimer’s, agrees with Medicare’s proposed restrictions on Aduhelm.Amanda Lucier for The New York TimesHe participated in an aducanumab trial, experiencing brain swelling and bleeding that required treatment in an intensive care unit. “I want aducanumab to be successful, and I really think that it might be useful,” he said. However, he added, he considers Medicare’s proposed restrictions appropriate.He called the Alzheimer’s Association campaign “shocking and irresponsible” and said he’ll stop donating to the organization, except for his local chapter. “The vast majority of experts in Alzheimer’s are not on the side of the Alzheimer’s Association,” he said.Several members of the association’s scientific and medical advisory group said they had concluded the drug shouldn’t yet be approved. Still, the association pushed for approval.The F.D.A. itself acknowledged the unclear benefit when it greenlighted Aduhelm under “accelerated approval,” which allows authorization of unproven drugs for serious diseases with few treatments, if the drug affects a biological mechanism in a way considered “reasonably likely to predict clinical benefit.”The agency’s justification was that Aduhelm targets a protein, amyloid, that forms plaques in the brains of Alzheimer’s patients. But many Alzheimer’s experts say that years of data have not shown that reducing amyloid can slow cognitive decline.In the association staff meeting, Dr. Carrillo described experts who criticized Aduhelm’s approval as “naysayers” who “are mainly anti-amyloid researchers, in conflict, in my view.”Several scientists critical of Aduhelm’s approval support the idea that targeting amyloid might help patients; they simply found Aduhelm’s results unconvincing.Mr. Egge, the chief public policy officer, did say at one meeting: “It’s not certain that this first treatment will work, certainly, for everybody, but it could.” He said that it’s common to have “first treatments making marginal differences” but that later drugs often work better. Mr. Johns said the association and its lobbying affiliate, the Alzheimer’s Impact Movement, have spent hundreds of thousands of dollars on the campaign.At the staff meeting, Mr. Johns addressed another issue: “Of course, you’ll hear people claim that we’re doing this because we receive some funding from the pharmaceutical industry or these companies.”He said corporate contributions “are very small, less than 1 percent of our total revenue,” adding, “We would never be affected by any kind of fund-raising.”One attendee asked: “Since the amount of funding we receive from biotech companies is so low, why not refuse to take it and take away the appearance of possible conflicts of interest?”Mr. Johns replied, “We’ve contemplated this many times,” but concluded it would have unintended consequences, like preventing the organization from accepting corporate matching contributions for participants in association fund-raising walks who happened to work at pharmaceutical companies.In the interview, Mr. Johns echoed these explanations. Asked if association officials had communicated with Biogen since Medicare’s proposal, he said, “I think probably some of our folks have had a conversation or more along the way” and that Biogen’s staff “occasionally pass along a piece of information, but I can tell you that we just don’t coordinate with them.”In the recordings, association officials told advocates that their annual meetings with local members of Congress would involve different “asks” than usual: They should request that lawmakers give a floor speech, write to C.M.S., or post on social media to urge Medicare to broadly cover Aduhelm and any other F.D.A.-approved Alzheimer’s treatment.One official, Jennifer Pollack, suggested that advocates should give congressional staff a “leave-behind” that included a sample letter, and social media posts drafted by the association and “sample talking points for a floor speech.”Kate Johnson, another official, told advocates: “If you do not know the answer to a question, that is totally OK.” In that case, “please always revert to our safest phrase,” which, she said, was: “‘I’m not sure, but I can pass that question on to a staffer at the Alzheimer’s Association who can provide some more information.’”She also urged advocates to take photos or screenshots of the congressional meetings to post on social media, tagging the lawmaker to show “we’re not going to give up on the issues that we’re passionate about.”Christopher Masak, director of advocacy, role-played being an Alzheimer’s patient’s son meeting with a lawmaker.“My mom is living with a fatal disease, and the bottom line is, I want more time,” his character said, adding, “Thinking of people like my mom who can’t access this medication, it just, it breaks my heart.”Medicare officials said that limiting coverage to clinical trial participants is especially important because Aduhelm is intended for people with early mild disease, who could potentially be sacrificing years of remaining function and quality of life if a drug’s harms outweigh any benefit.Mr. Johns said he understood the view that “risk could be better tolerated later in the disease” but said that the milder early period is the time many people most want to try to extend. C.M.S. officials also said Aduhelm data isn’t sufficiently representative because most trial participants were white, while Blacks and Latinos have greater Alzheimer’s risk. So, Medicare’s proposal requires that new clinical trials reflect racial and ethnic diversity.Association officials said Medicare’s proposal could have the opposite effect because people in underserved communities might have less access to clinical trial sites.A few issues mentioned by advocacy groups have also been raised by those who don’t oppose limiting coverage for Aduhelm. One is that, as currently worded, Medicare’s decision would apply to all monoclonal antibodies for Alzheimer’s, several of which are in late-stage trials and may soon be considered for F.D.A. approval.“It is essentially denying access to all current and future F.D.A.-approved treatments targeting amyloid in those living with Alzheimer’s disease,” Ms. Pollack said in one recording.The American Academy of Neurology wrote to C.M.S. calling the proposal to cover only patients in clinical trials “prudently designed to investigate the safety and effectiveness,” but asked that it be limited only to Aduhelm. In a statement, a C.M.S. spokeswoman, Beth Lynk, said coverage criteria could be re-evaluated for subsequent monoclonal antibodies. “C.M.S. intends to be nimble and respond to new evidence as it is made available — especially related to the clinical benefit of future therapeutics,” she said.Mr. Johns, who said that he recently attended three meetings with C.M.S. officials, including one with the agency’s administrator, indicated in the interview that the association wouldn’t be satisfied if Medicare’s restrictions applied only to Aduhelm, saying, “We absolutely believe there is sufficient evidence to provide coverage for the first approved treatment.”Advocacy groups’ efforts have gotten some lawmakers’ attention. Recently, a bipartisan group of 40 House members wrote asking C.M.S. to provide broad coverage.Earlier, 78 House Republicans sent a letter criticizing C.M.S.’s proposal, quoting the Alzheimer’s Association and UsAgainstAlzheimer’s. Both advocacy groups were described on Senator Susan Collins’s website as supporting a letter she and another Republican, Senator Shelley Moore Capito, wrote.Some lawmakers, including Democrats, have tweeted a version of the association’s language.But other lawmakers praised Medicare’s proposal, including Representatives Carolyn B. Maloney and Frank Pallone, Democrats who chair committees investigating the F.D.A.’s approval of Aduhelm.Mr. Johns said he didn’t know of any lawmakers who had switched from supporting to opposing Medicare’s proposal. But he said the association’s congressional meetings “have had positive outcomes, even for people who might still have a different opinion. There is at least a different level of understanding.”He declined to provide the number of tweets, letters or other measures of the campaign’s reach, saying: “There are those who are working against access. We are not inclined to share details of our tactical approaches with them. Our activities will be measured by outcomes that grant those with Alzheimer’s disease access to current and future F.D.A.-approved treatments without unnecessary barriers.”

Covid-19 may cause greater loss of gray matter and tissue damage in the brain than naturally occurs in people who have not been infected with the virus, a large new study finds.The study, published Monday in the journal Nature, is believed to be the first involving people who underwent brain scans both before they contracted Covid and months after. Neurological experts who were not involved in the research said it was valuable and unique, but they cautioned that the implications of the changes were unclear and did not necessarily suggest that people might have lasting damage or that the changes might profoundly affect thinking, memory or other functions.The study, involving people aged 51 to 81, found shrinkage and tissue damage primarily in brain areas related to sense of smell; some of those areas are also involved in other brain functions, the researchers said.“To me, this is pretty convincing evidence that something changes in brains of this overall group of people with Covid,” said Dr. Serena Spudich, chief of neurological infections and global neurology at the Yale School of Medicine, who was not involved in the study.But, she cautioned: “To make a conclusion that this has some long-term clinical implications for the patients I think is a stretch. We don’t want to scare the public and have them think, ‘Oh, this is proof that everyone’s going to have brain damage and not be able to function.’”

The data, released in a report Thursday, is a sign that medication abortion has become the most accessible and preferred method for terminating pregnancy.More than half of recent abortions in the United States were carried out with abortion pills, according to preliminary data released on Thursday, a sign that medication abortion has increasingly become the most accessible and preferred method for terminating pregnancy.The report, issued by the Guttmacher Institute, a research organization that supports abortion rights, found that in 2020, medication abortion — a two-pill method authorized in the United States for pregnancies up to 10 weeks’ gestation — accounted for 54 percent of all abortions. The figure represents a substantial increase from the institute’s previous report, which found that the method accounted for 39 percent of abortions in 2017.The increase in medication abortion is most likely the result of several factors. The method — which is less expensive and less invasive than surgical abortions — had already become increasingly common before the coronavirus pandemic, driven partly by restrictions from conservative states that imposed hurdles to surgical methods, especially later in pregnancy.As of 2017, according to the Guttmacher Institute, which collects data by contacting every known abortion provider in the country, nearly a third of clinics offered only medication abortion. In 2019, according to data from the Centers for Disease Control and Prevention, which did not include California, Maryland and New Hampshire, pills accounted for 42 percent of all abortions — and 54 percent of abortions that were early enough to qualify for medication because they occurred before 10 weeks’ gestation.The pandemic fueled that trend, as medical groups filed a lawsuit asking the federal government to lift the Food and Drug Administration’s requirement that the first of the two abortion pills, mifepristone, be dispensed to patients in person at a clinic or doctor’s office. Citing years of data showing that medication abortion is safe, the medical groups said that patients faced a greater risk of being infected with the coronavirus if they had to visit clinics to obtain mifepristone and pointed out that mifepristone was the only drug that the F.D.A. required patients to get in person from a medical provider but that patients were also allowed to take at home on their own without having the provider present.A judge granted the request that summer, allowing patients to see a physician by telemedicine and receive pills by mail, but, after a challenge by the Trump administration, the Supreme Court reinstated the restriction early last year.Under the Biden administration, however, the F.D.A. permanently lifted the in-person requirement in December and also said that pharmacies could begin dispensing mifepristone if they met certain qualifications. The F.D.A.’s action means that medication abortion will become more available to women who find it difficult to travel to an abortion provider or prefer the privacy of being able to terminate a pregnancy in their homes.As a result, while the new report from the Guttmacher Institute is preliminary — only reflecting information from 75 percent of the clinics and including only percentages, not raw data — the proportion of abortions carried out with pills is expected to increase further.Nearly 80 percent of all abortions in the C.D.C.’s 2019 data occurred before 10 weeks’ gestation, suggesting that there were many more women who might choose abortion pills over an in-clinic procedure if they could.At the same time, the growing interest in medication abortion has made it a focus of the highly polarized abortion debate.In 19 states, mostly in the South and the Midwest, telemedicine visits for medication abortion are banned, and so far in 2022, according to the Guttmacher Institute report, 16 state legislatures have introduced bills to ban or limit medication abortion.With the Supreme Court now considering whether to roll back abortion rights or even overturn the 1973 Roe v. Wade decision, which legalized abortion, experts and advocates on all sides expect medication abortion to play an even more pivotal role in the divisive abortion debate.

Though public health experts have long advised the use of condoms for anal sex to protect against H.I.V. and other infections, regulators did not have enough data to allow marketing for that use.For the first time, U.S. regulators have officially authorized a condom to be used for anal sex, not just vaginal sex.The decision, announced by the Food and Drug Administration on Wednesday, has long been sought by sexual health experts, who said it could encourage more people who engage in anal sex to use condoms to protect themselves against H.I.V. and other sexually transmitted infections.The risk of sexually transmitted diseases is “significantly higher” during anal sex than vaginal sex, an F.D.A. official said Wednesday. But until now, there has not been enough data to show that condoms are safe and effective during anal sex.“The F.D.A.’s authorization of a condom that is specifically indicated, evaluated and labeled for anal intercourse may improve the likelihood of condom use during anal intercourse,” Courtney Lias, director of the F.D.A. office that issued the approval, said in a statement. The decision applies to a condom manufactured by Global Protection Corp. called the ONE male condom. Last year, the company asked the F.D.A. to allow it to add anal sex to the intended use of the condom on the product label, based on a study showing the failure rate, defined as slippage or breakage, to be less than 1 percent during anal sex.The F.D.A. said in the statement that other condom companies would now be able to apply for similar approval by submitting claims that their condoms demonstrated “substantial equivalence” to the evidence shown for ONE condoms.“I don’t think this is viewed as something that should be restricted, but rather something that opens the door for other companies to rigorously assess their condoms and show that they also perform well for anal sex,” said Aaron Siegler, an epidemiologist at Emory University who helped lead the study that prompted the F.D.A. decision.Davin Wedel, president and founder of Global Protection Corp, said, “I think most people would be surprised to know that condoms are not approved for anal sex. With this new designation from the FDA, consumers will have important information about the safety and effectiveness of condoms for anal sex.”The federal agency had previously said that condoms needed to have less than a 5 percent failure rate, and earlier studies of condoms for anal sex had shown failure rates higher than that.As a result, while using condoms for anal sex is recommended by public health authorities like the World Health Organization and the Centers for Disease Control and Prevention, it has been considered an “off-label” use in the United States. Companies have not been able to market condoms for anal sex, said Dr. Kenneth Mayer, the medical research director for Fenway Health, a community health center in Massachusetts that has long been a leader in treating patients who identify as L.G.B.T.Q.“It’s a great thing if the package inserts could indicate anal sex because it might create an incentive for the companies to do more marketing,” Dr. Mayer said. “You don’t see condom ads on gay social media, for example, so this would incentivize that as part of part of the conversation.”“And it’s not just gay men.” Dr. Mayer continued. “It’s not that heterosexuals who engage in anal sex are unaware that condoms exist, but there’s been very little education, so it’s somewhat out of sight out of mind.”Condom use during anal sex has declined in recent years, since the advent of a method to prevent H.I.V. infection called pre-exposure prophylaxis, or PrEP, which involves taking a daily pill. According to the most recent statistics from C.D.C.’s National H.I.V. Behavioral Surveillance data, about 46 percent of men who have sex with men were having anal sex without condoms in 2017, compared to 28-to-40 percent in 2011.But although PrEP is very effective, there can be issues with cost and access. Currently, only about a third of men who are at high risk for H.I.V. infection are taking the drug, the C.D.C. reported.“That’s hundreds of thousands of people,” said Dr. Mayer, who was not involved in the study that led to the F.D.A.’s decision. “And certainly those are individuals who would benefit from condoms.”He added that condoms are the most effective protection against other sexually transmitted infections, including syphilis, which has been increasing in the United States.To try to amass data that could lead to the approval of condoms for anal sex, the company teamed up with researchers at Emory University, met with the F.D.A. and designed a study.Funded by the National Institutes of Health, the study, the largest to date on condom effectiveness during anal sex, was conducted between May 2016 and May 2017. It involved 504 men, half of whom had sex with men and half of whom had sex with women, and the researchers took several steps designed to encourage more consistent and accurate data than previous studies, Dr. Siegler said.After being trained in proper condom use, the men were given condoms and asked to fill out a daily diary on a phone app, to answer questions about whether they had had sex that day and whether the condom they used broke or slipped. The participants reported 2,351 anal and 2,533 vaginal sex acts during the study period.Dr. Siegler said that the team had hypothesized that the condom failure rate during anal sex would be low enough to pass muster with the F.D.A., but had not expected it to be as low as it was — 0.7 percent — or that it would be lower than the failure rate during vaginal sex, which was 1.9 percent.The researchers attribute the higher failure rate during vaginal sex to the fact that the study encouraged lubricant appropriate for condoms to be used for every instance of anal sex, but, adhering to public health guidelines, only encouraged lubricant to be used during vaginal sex “as needed or desired.” So, while 98 percent of people who had anal sex used lubricant, only 42 percent of those who had vaginal sex did. When the researchers looked only at people who used lubricant, the failure rate in the vaginal group was 1.1 percent, making the odds of failure in each group essentially the same, the study reported.Public health experts said that suggests that lubricant was critical to the study’s results, and in its statement, the F.D.A. said that during anal sex, the condom “should be used with a condom-compatible lubricant.”The study involved three different types of the One condom — standard, thin and fitted, which comes in 54 different sizes. They did not have ribbing or other characteristics, Dr. Siegler said. Each participant was given five samples of each type of condom to use for two to four weeks. The researchers had expected the fitted condoms to have the lowest failure rate, but the study found there was no difference, an outcome that Dr. Siegler said he thought reflected that all three varieties had to meet the same manufacturing and durability standards.Dr. Siegler, who specializes in research on PReP, said that before conducting the condom study, the Emory team wondered whether adding anal sex to a condom label would encourage more men to use condoms.“Does this matter? Would it change use?” he asked. The team conducted a survey of more than 10,000 men who had sex with men and found that 69 percent said that if the F.D.A. approved condoms for anal sex, they would be more encouraged to use them.“I don’t see condoms versus PReP as kind of mutually exclusive options, I see them as options that can support each other and that allow people that choice,” he said. “There isn’t perfect use of any one technology. But if we optimize people’s access to and understanding of different prevention options, I think we can increase the overall population level protection against H.I.V.”Dr. Mayer said he also saw adding the label to condoms as an additional tool that could help improve the use of all protective measures.“It’s definitely not a one-size-fits-all kind of kind of environment,” Dr. Mayer said. “It will help normalize the conversation because there’ll be an economic incentive for the companies to advertise condoms for anal sex.”

Social isolation, economic stress, loss of loved ones and other struggles during the pandemic have contributed to rising mental health issues like anxiety and depression.But can having Covid itself increase the risk of developing mental health problems? A large new study suggests it can.The study, published Wednesday in the journal The BMJ, analyzed records of nearly 154,000 Covid patients in the Veterans Health Administration system and compared their experience in the year after they recovered from their initial infection with that of a similar group of people who did not contract the virus.The study included only patients who had no mental health diagnoses or treatment for at least two years before becoming infected with the coronavirus, allowing researchers to focus on psychiatric diagnoses and treatment that occurred after coronavirus infection.People who had Covid were 39 percent more likely to be diagnosed with depression and 35 percent more likely to be diagnosed with anxiety over the months following infection than people without Covid during the same period, the study found. Covid patients were 38 percent more likely to be diagnosed with stress and adjustment disorders and 41 percent more likely to be diagnosed with sleep disorders than uninfected people.“There appears to be a clear excess of mental health diagnoses in the months after Covid,” said Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, who was not involved in the study.

A new, large study found that in the year after getting Covid, people were significantly more likely to be diagnosed with psychiatric disorders they hadn’t had than people who didn’t get infected.Social isolation, economic stress, loss of loved ones and other struggles during the pandemic have contributed to rising mental health issues like anxiety and depression.But can having Covid itself increase the risk of developing mental health problems? A large new study suggests it can.The study, published Wednesday in the journal The BMJ, analyzed records of nearly 154,000 Covid patients in the Veterans Health Administration system and compared their experience in the year after they recovered from their initial infection with that of a similar group of people who did not contract the virus.The study included only patients who had no mental health diagnoses or treatment for at least two years before becoming infected with the coronavirus, allowing researchers to focus on psychiatric diagnoses and treatment that occurred after coronavirus infection.People who had Covid were 39 percent more likely to be diagnosed with depression and 35 percent more likely to be diagnosed with anxiety over the months following infection than people without Covid during the same period, the study found. Covid patients were 38 percent more likely to be diagnosed with stress and adjustment disorders and 41 percent more likely to be diagnosed with sleep disorders than uninfected people.“There appears to be a clear excess of mental health diagnoses in the months after Covid,” said Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, who was not involved in the study. He said the results echoed the emerging picture from other research, including a 2021 study on which he was an author, and “it strengthens the case that there is something about Covid that is leaving people at greater risk of common mental health conditions.”The data does not suggest that most Covid patients will develop mental health symptoms. Only between 4.4 percent and 5.6 percent of those in the study received diagnoses of depression, anxiety or stress and adjustment disorders.“It’s not an epidemic of anxiety and depression, fortunately,” Dr. Harrison said. “But it’s not trivial.”Researchers also found that Covid patients were 80 percent more likely to develop cognitive problems like brain fog, confusion and forgetfulness than those who didn’t have Covid. They were 34 percent more likely to develop opioid use disorders, possibly from drugs prescribed for pain, and 20 percent more likely to develop non-opioid substance use disorders including alcoholism, the study reported.After having Covid, people were 55 percent more likely to be taking prescribed antidepressants and 65 percent more likely to be taking prescribed anti-anxiety medications than contemporaries without Covid, the study found.Overall, more than 18 percent of the Covid patients received a diagnosis of or prescription for a neuropsychiatric issue in the following year, compared with less than 12 percent of the non-Covid group. Covid patients were 60 percent more likely to fall into those categories than people who didn’t have Covid, the study found.The study found that patients hospitalized for Covid were more likely to be diagnosed with mental health issues than those with less serious coronavirus infections. But people with mild initial infections were still at greater risk than people without Covid.“Some people always argue that ‘Oh, well, maybe people are depressed because they needed to go to the hospital and they spent like a week in the I.C.U.,’” said the senior author of the study, Dr. Ziyad Al-Aly, chief of research and development at the V.A. St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis. “In people who weren’t hospitalized for Covid-19, the risk was lower but certainly significant. And most people don’t need to be hospitalized, so that is really the group that’s representative of most people with Covid-19.”The team also compared mental health diagnoses for people hospitalized for Covid with those hospitalized for any other reason. “Whether people were hospitalized for heart attacks or chemotherapy or whatever other conditions, the Covid-19 group exhibited a higher risk,” Dr. Al-Aly said.The study involved electronic medical records of 153,848 adults who tested positive for the coronavirus between March 1, 2020, and Jan. 15, 2021, and survived for at least 30 days. Because it was early in the pandemic, very few were vaccinated before infection. The patients were followed until Nov. 30, 2021. Dr. Al-Aly said his team was planning to analyze whether subsequent vaccination modified people’s mental health symptoms, as well as other post-Covid medical issues the group has studied.The Covid patients were compared with more than 5.6 million patients in the Veterans system who did not test positive for the coronavirus and more than 5.8 million patients from before the pandemic, in the period spanning March 2018 through January 2019. To try to gauge the mental health impact of Covid-19 against that of another virus, the patients were also compared with about 72,000 patients who had the flu during the two and a half years before the pandemic. (Dr. Al-Aly said there were too few flu cases during the pandemic to provide a contemporaneous comparison.)The researchers tried to minimize differences between groups by adjusting for many demographic characteristics, pre-Covid health conditions, residence in nursing homes and other variables.In the year after their infection, the Covid patients had higher rates of mental health diagnoses than the other groups.“It’s not really surprising to me because we’ve been seeing this,” said Dr. Maura Boldrini, an associate professor of psychiatry at NewYork-Presbyterian Columbia University Medical Center. “It’s striking to me how many times we’ve seen people with these new symptoms with no previous psychiatric history.”Most veterans in the study were men, three-quarters were white and their average age was 63, so the findings may not apply to all Americans. Still, the study included over 1.3 million women and 2.1 million Black patients, and Dr. Al-Aly said “we found evidence of increased risk regardless of age, race or gender.”There are several possible reasons for the increase in mental health diagnoses, Dr. Al-Aly and outside experts said. Dr. Boldrini said she believed the symptoms were most likely influenced by both biological factors and the psychological stresses associated with having an illness.“In psychiatry, it almost always is an interplay,” she said.Research, including brain autopsies of patients who died of Covid-19, has found evidence that Covid infection can generate inflammation or tiny blood clots in the brain, and can cause small and large strokes, said Dr. Boldrini, who has conducted some of these studies. In some people, the immune response that is activated to fight against a coronavirus infection may not shut down effectively once the infection is gone, which can fuel inflammation, she said.“Inflammatory markers can disrupt the ability of the brain to function in many ways, including the ability of the brain to make serotonin, which is fundamental for mood and sleep,” Dr. Boldrini said.By themselves, such brain changes may or may not cause psychological problems. But, if someone is experiencing stress from having felt physically ill or because having Covid disrupted their lives and routines, she said, “you may be more prone to not being able to cope because your brain is not functioning 100 percent.”Dr. Harrison, who has conducted other studies with large electronic medical databases, noted that such analyses can miss more granular information about patients. He also said that some people in the comparison groups might have had Covid and not been tested to confirm it, and that some Covid patients might have been more likely to receive diagnoses because they were more worried about their health after Covid or because doctors were quicker to identify psychological symptoms.“There’s no one analysis that tells you the whole story,” Dr. Al-Aly said. “Maybe all of us or most of us experienced some sort of an emotional distress or mental health stress or some sleep problem,” he added. “But people with Covid did worse.”

If further study confirms the findings, they could lead to ways to prevent and treat the complex condition.It is one of many mysteries about long Covid: Who is more prone to developing it? Are some people more likely than others to experience physical, neurological or cognitive symptoms than can emerge, or linger for, months after their coronavirus infections have cleared?Now, a team of researchers who followed more than 200 patients for two to three months after their Covid diagnoses report that they have identified biological factors that might help predict if a person will develop long Covid.The study, published Tuesday by the journal Cell, found four factors that could be identified early in a person’s coronavirus infection that appeared to correlate with increased risk of having lasting symptoms weeks later.The researchers said they had found that there was an association between these factors and long Covid (which goes by the medical name post-acute sequelae of Covid-19, or PASC) whether the initial infection was serious or mild. They said that the findings might suggest ways to prevent or treat some cases of long Covid, including the possibility of giving people antiviral medications soon after an infection has been diagnosed.“It’s the first real solid attempt to come up with some biologic mechanisms for long Covid,” said Dr. Steven Deeks, a professor of medicine at the University of California, San Francisco, who was not involved in the study.He and other experts, along with the study authors themselves, cautioned that the findings were exploratory and would need to be verified by considerably more research.Still, Dr. Deeks said: “They’ve identified these four major factors. Each is biologically plausible, consistent with theories that other people are pursuing, and importantly, each is actionable. If these pathways get confirmed, we as clinicians can actually design interventions to make people better. That is the take-home message.”One of the four factors researchers identified is the level of coronavirus RNA in the blood early in the infection, an indicator of viral load. Another is the presence of certain autoantibodies — antibodies that mistakenly attack tissues in the body as they do in conditions like lupus and rheumatoid arthritis. A third factor is the reactivation of Epstein-Barr virus, a virus that infects most people, often when they are young, and then usually becomes dormant.The final factor is having Type 2 diabetes, although the researchers and other experts said that in studies involving larger numbers of patients, it might turn out that diabetes is only one of several medical conditions that increase the risk of long Covid.“I think this research stresses the importance of doing measurements early in the disease course to figure out how to treat patients, even if we don’t really know how we’re going to use all that information yet,” said Jim Heath, the principal investigator of the study and president of the Institute for Systems Biology, a nonprofit biomedical research organization in Seattle.“Once you can measure something, then you may be able to start doing something about it,” Dr. Heath said, adding: “We did this analysis because we know patients will go to physicians and they’ll say that they’re tired all the time or whatever, and the physician just tells them to get more sleep. That’s not very helpful. So, we wanted to actually have a way to quantify and say that there’s actually something wrong with these patients.”The complex study had several components and involved dozens of researchers at several universities and centers including the Institute for Systems Biology, the University of Washington and Swedish Medical Center in Seattle, where the study’s lead medical author, Dr. Jason Goldman, is an infectious disease specialist.The primary group of patients included 209 people, ages 18 to 89, who were infected with the coronavirus during 2020 or early 2021 and were seen at Swedish Medical Center or an affiliated clinic. Many were hospitalized for their initial infections, but some were seen only as outpatients. Researchers analyzed blood and nasal swabs when patients were diagnosed, during the acute phase of their infections and two to three months later.A tattoo of the demon Mr. Gillotte hallucinated during the Covid delirium he experienced after he was taken off the ventilator.Joshua Bright for The New York TimesThey surveyed the patients about 20 symptoms associated with long Covid, including fatigue, brain fog and shortness of breath, and corroborated those reports with electronic health records, Dr. Heath said.He said that 37 percent of the patients had reported three or more symptoms of long Covid two or three months after infection. A further 24 percent reported one or two symptoms, and 39 percent reported no symptoms. Of patients reporting three or more symptoms, 95 percent had one or more of the four biological factors identified in the study when they were diagnosed with Covid-19, Dr. Heath said.The most influential factor appeared to be autoantibodies, which were associated with two-thirds of the cases of long Covid, Dr. Heath said. Each of the other three factors showed up in about a third of the cases, he said, and there was considerable overlap, with several factors identified in some patients.The researchers corroborated some of their findings in a separate group of 100 patients, many with mild initial infections, from research led by Dr. Helen Chu at the University of Washington. The researchers also compared their results to data from 457 healthy people.“The study is large and comprehensive and is a great resource for the community studying long Covid,” said Akiko Iwasaki, an immunologist at Yale, who was not involved in the research.Dr. Avindra Nath, who is chief of the section on infections of the nervous system at the National Institute of Neurological Disorders and Stroke and was not involved in the study, called the study well designed but pointed out several weaknesses, including the fact that patients had been followed for only two to three months. “This might be too short a time frame,” he said. “Some might just improve spontaneously with time.”Dr. Iwasaki noted that 71 percent of the patients in the primary group had been hospitalized, limiting the ability to conclude that the biological factors were equally relevant for people with mild initial infections. The Coronavirus Pandemic: Key Things to KnowCard 1 of 4Omicron in retreat.

If the preliminary decision is finalized this spring, it would sharply limit the number of patients who use the expensive drug.Medicare officials have decided that the federal health insurance program should only cover the controversial new Alzheimer’s drug Aduhelm for patients who are participating in approved clinical trials. The preliminary decision, reached after lengthy deliberations, was released on Tuesday by the Center for Medicare and Medicaid Services, or C.M.S. If it is finalized later this year, it would significantly limit the number of patients who could use the expensive drug.The decision said that coverage should be provided for patients in “C.M.S. approved randomized controlled trials” and trials supported by the National Institutes of Health. The decision said “all trials must be conducted in a hospital-based outpatient setting.”The agency added that Aduhelm of other similar drugs for Alzheimer’s that are provided outside of these trials “are nationally non-covered.”“Alzheimer’s disease is a devastating illness that has touched the lives of millions of American families. Throughout this National Coverage Determination process, CMS has been and remains committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients,” said the C.M.S. administrator, Chiquita Brooks-LaSure. “C.M.S. has proposed an evidence-based coverage policy after experts reviewed all relevant publicly available evidence and feedback received from stakeholders.”Whether Medicare ends up covering Aduhelm is considered pivotal to the future of the drug, which is made by Biogen and priced at $28,200 a year per patient. Roughly 80 percent of the 1.5 million Americans who have the type of condition the F.D.A. approved the drug to treat — mild Alzheimer’s-related cognitive decline — are old enough to receive coverage under Medicare.For the next 30 days, C.M.S. will have a public comment period on the preliminary decision, and the agency is expected to announce its final decision about covering the drug by mid-April.The fact that Medicare is conducting an extensive review of Aduhelm is itself unusual. The program almost always pays for F.D.A.-approved drugs, at least for the medical conditions designated on their label, health policy experts said.Biogen initially priced the drug at $56,000 a year, but slashed the price in half last month after months of weak sales. Before Biogen’s price cut, Medicare’s actuarial division, acting without knowing what the coverage decision would be, imposed one of the biggest-ever increases in Medicare Part B premiums for 2022, partly driven by the possibility of Aduhelm coverage.After Biogen’s price cut, advocacy groups for Alzheimer’s patients urged C.M.S. to lower the premium increase. On Monday, the secretary for health and human services, Xavier Becerra, said that he was instructing C.M.S. to re-examine the premium hike “given the dramatic price change of the Alzheimer’s drug, Aduhelm.”Aduhelm was approved by the Food and Drug Administration in June in a decision vigorously criticized by many doctors and Alzheimer’s experts because clinical trial results showed it had significant safety risks and unclear benefit to patients.Congress is investigating whether the F.D.A. worked too closely with Biogen and why Aduhelm was approved despite strong objections from some senior F.D.A. officials and the agency’s independent advisory committee.So far, only a small number of patients — a fraction of the number Biogen and industry analysts had initially expected — have used Aduhelm, a monoclonal antibody administered as a monthly infusion. Many large American health care systems have declined to offer the drug, citing questions about its benefits and risks. Medicare officials are supposed to determine coverage based on whether a drug is a “reasonable and necessary” treatment, a phrase that usually “means adequate evidence of improved health outcomes,” said Dr. Sean Tunis, a former official with C.M.S. who is now a senior fellow at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center.Medicare’s decision on Aduhelm will also establish standards for evaluating several similar Alzheimer’s drugs in the pipeline.The F.D.A. itself acknowledged in its approval of Aduhelm that there was insufficient evidence it would help patients. Instead, it greenlighted the medication — the first new treatment for Alzheimer’s in 18 years — under a program called “accelerated approval,” which allows authorization of unproven drugs for serious diseases with few treatment options if the drug affects a biological mechanism in a way considered “reasonably likely to predict clinical benefit.”The F.D.A. said it based accelerated approval on Aduhelm’s reduction of a protein, called amyloid, that clumps into plaques in the brains of people with Alzheimer’s. But many Alzheimer’s specialists say that extensive research has shown little evidence that reducing amyloid slows cognitive decline. The F.D.A. also required Biogen to conduct another clinical trial to determine if the drug provided any evidence of benefit. In the years it will take for that trial to be completed, Aduhelm will be available to patients.

A group of Alzheimer’s experts and health advocates called on the F.D.A. to withdraw its approval of the drug, the latest of several setbacks for the treatment.Biogen slashed the price of its controversial new Alzheimer’s drug Aduhelm on Monday as the drug faces weak sales and mounting criticism.The price was reduced to $28,200 a year from $56,000 on the same day that a group of Alzheimer’s experts and health advocates called on the Food and Drug Administration to pull the drug off the market and said they were supporting an effort to file a formal petition with the agency to withdraw it.“The F.D.A.’s decision to approve Aduhelm is indefensible in both scientific and clinical terms,” said a statement signed by 18 scientists, most of them doctors. “This drug should be withdrawn from the market immediately.”The agency approved Aduhelm in June, even though a council of senior F.D.A. officials, an advisory committee of outside experts and many Alzheimer’s specialists said the scientific evidence showed that the drug did not provide a clear benefit to patients and that it carried risks of dangerous side effects.Major health systems, including Cleveland Clinic, Mount Sinai Health System, Mass General Brigham and the Department of Veterans Affairs have declined to offer Aduhelm, citing questions about its benefits and risks. In October, Biogen reported that Aduhelm had brought in just $1.9 million in revenue through September, a strikingly small amount given that about 1.5 million Americans have the mild Alzheimer’s-related dementia that makes them eligible for the drug.In a statement about the price-cutting on Monday, Michel Vounatsos, Biogen’s chief executive officer, said the company had “listened to the feedback of our stakeholders” and believed that “too many patients are not being offered the choice of Aduhelm due to financial considerations.”But Brian Skorney, an analyst at Robert W. Baird & Company, said after the price announcement: “For the broad majority of people who are critical of Aduhelm, $56,000 and $28,000 are both exceptionally high prices for a drug that a lot of people perceive doesn’t work at all.”The statement from Alzheimer’s experts and health advocates calling on the F.D.A. to withdraw Aduhelm grew out of a three-hour video meeting among the scientists last week.“We’re not just saying the approval was probably the worst decision the F.D.A. ever made,” Dr. Peter Whitehouse, a neurologist and Alzheimer’s expert at Case Western Reserve University who led the Dec. 15 meeting, told attendees during the session. “It’s so bad that we should advocate for withdrawal.”The doctors and scientists who signed the statement also agreed to provide their expertise to support the filing of a citizen petition, a formal process to seek reversal of the F.D.A.’s decision. The petition will be filed by the Right Care Alliance, a coalition of clinicians, patients and community members, which is also circulating a pledge for physicians who promise not to prescribe Aduhelm and for patients and family members who say they will not request it.Dr. Vikas Saini, chairman of the Right Care Alliance and president of the Lown Institute, a health care think tank, said that while the citizen petition process can take months or years, it can prompt F.D.A. action.Dr. Saini, who helped organize last week’s meeting, said that out of 45 citizen petitions filed since 1971 by the group Public Citizen, in 27 cases the F.D.A. withdrew drugs from the market and in seven other cases the agency sharply restricted a drug’s use.In response to the call to withdraw approval of Aduhelm, also known by its scientific name, aducanumab, an F.D.A. spokeswoman said that “the data set for Aduhelm was very complex, and our review has been thorough.”The spokeswoman also said that “careful analyses of the Phase 2 and Phase 3 clinical trials support the conclusion that it is likely that Aduhelm provides clinical benefit — although the data currently available do not provide substantial evidence of effectiveness on clinical benefit.”Aduhelm has also been encountering resistance in other countries. On Friday, reviewers at the European Union’s drug regulator, the European Medicines Agency, recommended against approving Aduhelm, a decision that Biogen said it would ask to be re-examined.Aduhelm is a monoclonal antibody, given as a monthly infusion. In clinical trials, 41 percent of patients receiving the F.D.A.-approved higher dose experienced brain swelling or brain bleeding, often mild, but serious in some cases.Pool photo by Jessica RinaldiSeveral months ago, leading Canadian Alzheimer’s research organizations said that approving the drug in Canada “cannot be justified.”Dr. Howard Chertkow, scientific director of the Canadian Consortium on Neurodegeneration in Aging, was one of three Alzheimer’s experts from outside the United States who signed the statement calling on the F.D.A. to withdraw the drug. “We feel it’s an abrogation of our responsibility as physicians to allow a marginal medication with a very high cost associated with it to come into the country, so we’re quite active in trying to block what has happened in the states from occurring in Canada,” he said at last week’s meeting.Two nearly identical clinical trials of Aduhelm, a monoclonal antibody given as a monthly infusion, were stopped early because an independent data monitoring committee concluded that the drug didn’t appear to be beneficial. A later analysis by Biogen found that participants receiving the high dose of the drug in one trial had experienced a very slight slowing of cognitive decline but that participants in the other trial had not benefited at all.About 41 percent of patients receiving the high dose — the dose the F.D.A. approved — experienced brain swelling or brain bleeding, side effects that were often mild or asymptomatic, but were sometimes serious.Monday’s statement also objects to the F.D.A.’s justification for its approval. Acknowledging there was insufficient evidence that Aduhelm would help patients, the agency greenlighted it under a program called “accelerated approval,” which allows authorization of drugs without proof of benefit for serious diseases that have few treatment options if the drug affects part of the disease’s biology (known as a surrogate endpoint) in a way that is “reasonably likely to predict clinical benefit.”The F.D.A. based its approval on Aduhelm’s ability to reduce a protein called amyloid that forms plaques in the brains of people with Alzheimer’s. But experts say years of studies have not shown that reducing amyloid helps memory or thinking problems.Approving the drug because of amyloid reduction “will have huge and wide-ranging negative implications for patients, families” and dementia research, Dr. Kenneth Langa, a professor of medicine at the University of Michigan, said in last week’s meeting. The group’s statement, which includes a section for others to sign their names in support, plays on the F.D.A.’s language by calling for “accelerated withdrawal.”“Reading the justification of the F.D.A. was like watching a ‘Saturday Night Live’ skit for data nerds.” Dr. Saini said. “I mean, I had trouble believing it.”The agency’s approval requires that Biogen conduct another trial to see if Aduhelm works. In its response Monday, the F.D.A. spokeswoman said “we believe that the data support accelerated approval while holding the company accountable for conducting an additional study.” Last week, Biogen said that it had developed a protocol to get that trial completed in 2026, several years before the F.D.A.-imposed deadline.Before he signed Monday’s statement, Dr. Sam Gandy, director of Mount Sinai’s Center for Cognitive Health, who helped organize the meeting, said that with advocacy groups like the Alzheimer’s Association still supporting the drug’s approval, he had a “concern that calling for something may trigger a backlash that undoes where we really want to go.”But Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who also signed the statement, said that while it was unlikely that calling for withdrawal would make F.D.A. officials say, “‘Yeah, they’re right, we goofed, we better undo this decision,’” the action was nonetheless important. “We’re taking a stand and saying the process was terrible and the outcome was terrible, and even if they don’t listen to it, it’ll be kind of a shot across the bow.”Rebecca Robbins contributed reporting.

Scientists who injected idle mice with blood from athletic mice found improvements in learning and memory. The findings could have implications for Alzheimer’s research and beyond.What if something in the blood of an athlete could boost the brainpower of someone who doesn’t or can’t exercise? Could a protein that gets amplified when people exercise help stave off symptoms of Alzheimer’s and other memory disorders?That’s the tantalizing prospect raised by a new study in which researchers injected sedentary mice with blood from mice that ran for miles on exercise wheels, and found that the sedentary mice then did better on tests of learning and memory.The study, published Wednesday in the journal Nature, also found that the type of brain inflammation involved in Alzheimer’s and other neurological disorders was reduced in sedentary mice after they received their athletic counterparts’ blood.Scientific results with mice don’t necessarily translate to humans. Still, experts said the study supports a growing body of research.“We’re seeing an increasing number of studies where proteins from outside the brain that are made when you exercise get into the brain and are helpful for improving brain health, or even improving cognition and disease,” said Rudolph Tanzi, a professor of neurology at Massachusetts General Hospital and Harvard Medical School. He led a 2018 study that found that exercise helped the brains of mice engineered to have a version of Alzheimer’s.The most promising outcome would be if exercise-generated proteins can become the basis for treatments, experts said.“The demonstration that there are transferable factors in the blood that seemed to convey beneficial effects on the brain that improve learning and memory is by far the most interesting aspect of the work,” said Dr. Madhav Thambisetty, a neurologist and senior investigator at the National Institute on Aging, who was not involved in the new research.The study, led by researchers at Stanford School of Medicine, found that one protein — clusterin, produced in the liver and in heart muscle cells — seemed to account for most of the anti-inflammatory effects. But several experts noted that recent studies have found benefits from other proteins. They also said more needs to be learned about clusterin, which plays a role in many diseases, including cancer, and may have negative effects in early stages of Alzheimer’s before brain inflammation becomes dominant.“It’s far too premature to conclude that higher or lower levels of clusterin might be either beneficial or not,” said Dr. Thambisetty, who has studied clusterin. “I don’t think we’re at the stage yet where people can trade in their treadmills or cancel their gym memberships for a clusterin pill or a clusterin injection.”The study was led by Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford, who had previously done research finding that the blood of young mice can reverse age-related cognitive impairment in old mice.Dr. Wyss-Coray said he wanted to see “if exercise produced factors that would also accumulate in the blood and that you could then transfer them.”The study involved mice that were about three months old — roughly the equivalent of 25-to-30-years-old for humans. Some of the mice, nocturnal animals that love to run, could freely use exercise wheels in their cages and logged about four to six miles on the wheels each night. The wheels were locked for other mice that could scoot around their cages but could not get an extended cardio workout.After 28 days, the researchers took a third group of mice that also did not exercise and injected them with blood plasma, the liquid that surrounds blood cells, from either the runner mice or the non-runner mice. Mice receiving runner blood did better on two tests of learning and memory than those receiving blood from the non-runner mice.In one test, which measures how long a mouse will freeze in fear when it is returned to a cage where it previously received an electric foot shock, mice with runner blood froze 25 percent longer, indicating they had better memory of the stressful event, Dr. Wyss-Coray said. In the other test, mice with runner blood were twice as fast at finding a platform submerged in opaque water, he said.The team also found that the brains of mice with runner blood produced more of several types of brain cells, including those that generate new neurons in the hippocampus, a region involved in memory and spatial learning.A genetic analysis showed that about 1,950 genes had changed in response to the infusion of runner blood, becoming either more or less activated. Most of the 250 genes with the greatest activation changes were involved in inflammation and their changes suggested that brain inflammation was reduced.The team tested whether removing any of the four most significant proteins in the runner blood would matter, and found that if clusterin was removed, anti-inflammatory effects disappeared. And when mice engineered to have a type of brain inflammation or a version of Alzheimer’s were injected with clusterin, it lessened their brain inflammation.In the only part of the study involving humans, 20 military veterans with a pre-dementia condition called mild cognitive impairment who had participated in a six-month exercise program were found to have high levels of clusterin in their blood.Kaci Fairchild, associate director of the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center, and an author of the new study, said the veterans, ranging in age from 50 to 89, exercised three times a week, combining cardio with weight training.Dr. Fairchild said that in results that have not yet been published, besides having elevated clusterin, the veterans did better on tests involving word memory and story recall.“Across the board, veterans had improvements in cognitive function, largely related to learning and memory,” Dr. Fairchild said. Noting that some people have disabilities or limitations that prevent them from exercising, she said she hoped that “the implications from this clusterin is that we can develop a medication targeting this protein for persons who weren’t able to engage in physical activity.”In the brain, clusterin binds to cells that line the blood vessels, cells that become inflamed in Alzheimer’s disease, Dr. Wyss-Coray said, suggesting that a potential drug might bind to those cells and “mimic the anti-inflammatory effects.”Still, experts who study Alzheimer’s disease and neuroinflammation said much more research is needed before therapies can be developed.“Not everything that works in mice works in humans, and we don’t know if there are other unexpected side effects that could make it untenable in humans,” said Mark Gluck, a professor of neuroscience and public health at Rutgers University in Newark, N.J., who was not involved in the study.Dr. Michael Heneka, the incoming director of the Luxembourg Centre for Systems Biomedicine who was not involved in the study, said the role of inflammation in diseases processes can change over time, being protective early on and detrimental later, so it is important to target inflammation at the appropriate time.It’s also unclear if clusterin is the optimal protein for a therapy.Other proteins linked to physical exercise have been shown in recent studies to improve cognition in mice. One, irisin, released by muscles, was found to reduce neuroinflammation and help mice perform better on memory and learning tests. Another, called Gpld1, an enzyme produced in the liver, was shown to increase after exercise and to correlate with better cognitive function in elderly mice.Whichever proteins end up being promising, it would be safer to develop a medication than to try to transfuse blood, which would contain other things beside the proteins, said Dr. Tanzi, who was not involved in the new study. “The big question,” he added, “is which proteins are the winners and how do we take advantage of them to provide new therapies?”