Taub Institute: Genomics Core


Columbia University
Irving Medical Center
Neurological Institute

710 West 168th Street, 3rd floor
(212) 305-1818

bottom bar
make an appointment

Taub Institute news and events


2020 - 2019 | 2018 - 2011

    June 24, 2020
    By Meghan Rabbitt
    Researchers Explain Why Black Americans Are At Higher Risk For Alzheimer's
    The Alzheimer’s epidemic no one is talking about.

    Six years ago, Veronica Shanklin showed up at her childhood home in DeSoto, Texas, expecting a typical visit. Shanklin’s grandmother, who’d been diagnosed with Alzheimer’s disease at age 82, had moved in with Shanklin’s mom a few years earlier. Shanklin, a marketing executive in Chicago, wanted to spend some time with them and was also eager to help with caretaking for a few days; she was sure her mom, then 66, could use a break.

    Yet mere minutes after walking in the door, Shanklin’s heart sank. Both her grandmother and mother had lost weight. The usually tidy home was a mess, with dirty laundry piling up and overdue bills scattered across a bed.

    “My mom was the manager of the credit union at her church,” Shanklin says. “If she couldn’t pay her own bills or keep up with cooking and cleaning, I knew something was wrong.” Then Shanklin noticed that her mother kept forgetting what day it was. She’d seen her grandmother—and grandfather, who also had Alzheimer’s—deal with similar issues. Worried, Shanklin took her mom to the doctor. The diagnosis confirmed her fear: Alzheimer’s disease.

    Shanklin quit her job and moved to Texas. She took over caregiving for her mother and grandmother—preparing meals, keeping house, helping them get to doctor’s visits—all while making sure they didn’t wander out of the house or otherwise endanger themselves. “This disease has turned my life upside down,” Shanklin says. “And the fact that it’s touched two of my grandparents and my mom almost seems unfair.”

    Unfair, yes, but unfortunately not unusual. Shanklin’s family history is in line with some staggering statistics: Older African Americans are about twice as likely as older non-Hispanic white people to develop Alzheimer’s or other dementias, according to the Alzheimer’s Association. On top of that, less than 5 percent of participants in U.S. health studies are black, making it difficult to identify factors driving the disparity and find ways to address them.

    Scientists have tried to ascertain whether African Americans naturally make more beta-amyloid and tau proteins, two of the signature causes of Alzheimer’s. Beta-amyloid forms clumps in the brain that interfere with cell-to-cell communication, and tau creates so-called tangles inside brain cells. Both result in forgetfulness, confusion, difficulty concentrating, delusions, and other telltale symptoms of the disease. So far, there’s no evidence that African Americans have higher levels of beta-amyloid or tau, says Reisa A. Sperling, MD, a Harvard Medical School neurology professor and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital.

    “We have other theories, though,” says Lisa L. Barnes, PhD, a professor of gerontology and geriatric medicine at the Rush Alzheimer’s Disease Center at Rush University Medical Center and a trailblazer in researching the Alzheimer’s racial imbalance. Barnes and other experts point to the fact that Black Americans have higher rates of diabetes, hypertension, stroke, elevated cholesterol, and heart disease—all of which are correlated with Alzheimer’s dementia. These conditions also affect blood vessels and can impair blood flow, which can then damage the brain and may also contribute to beta-amyloid and tau protein buildup, thereby raising Alzheimer’s risk, explains Barnes.

    On top of that, “diabetic brains have difficulty utilizing and managing glucose and have more difficulty making new brain cells,” says Goldie S. Byrd, PhD, professor and director of the Maya Angelou Center for Health Equity at Wake Forest School of Medicine. All of these issues can lead to memory impairment, cognitive and behavioral changes, and other signs of Alzheimer’s, she says.

    In a 2015 study, Barnes and colleagues compared brain autopsies of black and white Alzheimer’s patients who had similar backgrounds (age, sex, education level, and cognitive ability). They found that the Black patients were more likely to have “mixed brain pathologies”—meaning that in addition to the expected signs of Alzheimer’s (beta-amyloid and tau proteins), they had conditions like arteriosclerosis and atherosclerosis, two forms of vascular disease.

    Even when scientists control for cardiovascular and related factors, however, Black Americans are still more susceptible to Alzheimer’s and other dementias. A 2017 JAMA Neurology study found that those born in states with high stroke death rates (Alabama, Alaska, Arkansas, Louisiana, Mississippi, Oklahoma, South Carolina, Tennessee, and West Virginia) had a 67 percent higher risk for dementia compared with non-Black participants born elsewhere, while non-Black subjects born in those states faced a 46 percent increased risk. “A theory holds that older African Americans who were exposed to segregation, which was prevalent in many of these states, experienced significant long-term stress, which could possibly contribute to a decline in cognitive function later in life,” says Rachel Whitmer, PhD, a principal investigator on the study and professor and associate director of the Alzheimer’s Disease Research Center at UC Davis School of Medicine.

    A growing body of research is exploring the links between long-term stress and racial discrepancies in dementia. Among other things, chronic stress contributes to inflammation and vascular disease, and can even directly damage the brain’s neurons. “This can lead to a slew of health issues, including atrophy in areas of the brain that are key for memory and cognition,” says Megan Zuelsdorff, PhD, an assistant professor at the University of Wisconsin-Madison School of Nursing investigating the mechanisms underlying cognitive health and dementia disparities.

    A recent study coauthored by Zuelsdorff found that stressful life events (financial insecurity, legal issues, divorce, being fired from a job, the death of a child) took a greater toll on the memory function of African Americans. For white participants, each stressful event was equivalent to about six additional months of normal aging; in Black participants, each of the same stressors added an additional year and a half. The study also found that African Americans reported 84 percent more stressful life events than their white counterparts.

    Stressful events not only have residual effects but can also add up over time. “When you’re dealing with a stressor or a challenging life situation, your physical, social, and financial resources can become depleted, making you more vulnerable to the next hit,” says Zuelsdorff. “Since disadvantage—economic, educational, societal—can be cumulative, we think it could be one reason for theAlzheimer’s disparity.” One of Barnes’s studies shows a direct link between the specific stress of discrimination and poor cognitive function, particularly memory. “We need more research in this area,” says Barnes.

    That’s where the work of Jennifer J. Manly, PhD, a professor of neuropsychology at Columbia University Irving Medical Center, comes in. When Manly and colleagues compared results of memory tests of African Americans and white Americans who had received the same quality of childhood education, they found no difference in the rate of cognitive decline over time. In other research, they found a decreasing trend of dementia among African Americans who benefited from access to more schooling and better education. There is hope that widespread legal and cultural intolerance for discrimination will eventually help even out risk levels. “Thanks to increasing educational equality, we believe there’s a good chance that we won’t see this disparity in the future,” says Whitmer.

    Shanklin, too, is looking toward then future—hers and that of other Black people. Her grandmother died in 2017, and her mother’s short-term memory has worsened. To try to avoid a similar fate, Shanklin eats healthfully and exercises regularly, habits that research has shown may help delay cognitive decline. She started a nonprofit, Dementia Care Warriors, that offers support to caregivers and signed up with the Alzheimer’s Association to be considered for related studies (see “Get Involved”). “Watching someone you love battle Alzheimer’s can make you feel helpless—and mad, considering African Americans are so much more affected,” she says.“I want to do whatever I can to help experts find the answers we need.”

    June 29, 2020
    New Eye Drops May Prevent a Common Cause of Blindness

    Researchers at Columbia University Irving Medical Center have developed eye drops that could prevent vision loss after retinal vein occlusion, a major cause of blindness for millions of adults worldwide.

    A study, in mice, suggests that the experimental therapy—which targets a common cause of neurodegeneration and vascular leakage in the eye—could have broader therapeutic effects than existing drugs.

    The study was published in Nature Communications.

    What is Retinal Vein Occlusion?

    Retinal vein occlusion occurs when a major vein that drains blood from the retina is blocked, usually due to a blood clot. As a result, blood and other fluids leak into the retina, damaging specialized light-sensing neurons called photoreceptors.

    Standard treatment for the condition currently relies on drugs that reduce fluid leakage from blood vessels and abnormal blood vessel growth. But there are significant drawbacks. These therapies require repeated injections directly into the eye, and for the patients who brave this daunting prospect, the treatment ultimately fails to prevent vision loss in the majority of cases.

    The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons, who led the studies. Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a tightly regulated mechanism for naturally eliminating damaged or excess cells.

    In studies of mice, the Troy lab discovered that when blood vessels are injured by retinal vein occlusion, caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina.

    Eye Drops Prevent Retinal Injury

    The Troy lab found that a highly selective caspase-9 inhibitor, delivered in the form of eye drops, improved a variety of clinical measures of retinal function in a mouse model of the condition. Most importantly, the treatment reduced swelling, improved blood flow, and decreased neuronal damage in the retina.

    “We believe these eye drops may offer several advantages over existing therapies,” says Troy. “Patients could administer the drug themselves and wouldn’t have to get a series of injections. Also, our eye drops target a different pathway of retinal injury and thus may help patients who do not respond to the current therapy.”

    Next Steps

    The researchers are preparing to test the eye drops in people with retinal vein occlusion during a phase I clinical trial.

    Moving forward, the Troy lab will also study whether caspase-9 inhibitors can be used to treat other vascular injuries caused by overactivation of the enzyme, including diabetic macular edema (another common cause of blindness) and stroke.

    “Vascular dysfunction is at the heart of many chronic neurological and retinal disorders, because high energy demands in the brain and eye render these tissues exceptionally vulnerable to disruption in blood supply,” says the study’s first author, Maria Avrutsky, PhD, postdoctoral research scientist in pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons.

    May 8, 2020
    Dr. Ted Huey Provides Guidance on FTD Care During COVID Pandemic

    As a member of the Association for Frontotemporal Degeneration (AFTD) Medical Advisory Council, Dr. Ted Huey addressed the national FTD community to outline the unique challenges of FTD care during the COVID-19 pandemic and provide guidance to FTD patients, families, and caregivers.

    March 31, 2020
    New COVID-19 Biobank at Columbia Opens for Researchers

    Columbia University Vagelos College of Physicians and Surgeons, in partnership with NewYork-Presbyterian Hospital, has established a COVID-19 Biobank as a centralized resource to collect, store, and disseminate biological specimens and clinical data for researchers at Columbia University and elsewhere.

    “Our vibrant research community is one of our strengths,” says Michael Shelanski, MD, PhD, senior vice dean for research at VP&S. “We’re coming together in this moment of uncertainty to improve our understanding of COVID-19 and use that understanding to improve how to diagnose, treat, and prevent it.”

    The COVID-19 Biobank at Columbia started collecting clinical samples in March from patients who have permitted use of their samples for research related to COVID-19. The Department of Pathology & Cell Biology has established a COVID-19 clinical pathological laboratory and will facilitate access to residual clinical samples.

    Researchers who wish to receive samples must submit an application that will be reviewed by the biobank’s governance committee.

    An executive committee convened by Shelanski and Muredach Reilly, MBBCh, director of the Irving Institute for Clinical and Translational Research and associate dean for clinical and translational research at VP&S, will establish procedures that ensure the COVID-19 Biobank will be a robust resource and data generated from these samples are shared broadly.

    More information for researchers and patients is available at the Columbia University Biobank website.

    Congratulations to Drs. Jennifer J. Manly, Olajide Williams, and Richard Mayeux, who were among the inaugural inductees into the Vagelos College of Physicians and Surgeons (VP&S) Academy of Community and Public Service. Modeled after the VP&S Virginia Apgar and Clinical Excellence academies, this latest program stems from the new Office of Community Service Programs, led by Dr. Rafael Lantigua, and recognizes medical school faculty who make substantial contributions to community and public health.

    November 22, 2019
    What Science Tells Us about Preventing Dementia

    In the 90s, Alzheimer’s researchers were full of optimism. New genetic studies all pointed to one culprit—hard clumps of protein, called amyloid, that litter the brains of people with the disease.

    With the emergence of the first tangible target, pharmaceutical companies jumped in to develop drugs to clear amyloid from the brain. In animals, the drugs appeared to improve memory. But the results of human clinical trials that followed were disheartening: One after one, these drugs—all designed to target amyloid—have failed to slow the disease.

    The onslaught of news about these failures has left the public wondering whether amyloid has anything to do with Alzheimer’s—and whether a new approach is needed.

    The field has already begun to redirect its focus, says Scott Small, MD, director of Columbia’s Alzheimer’s Disease Research Center and the Boris and Rose Katz Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons.

    “There’s now reason to be cautiously optimismistic,” he says, “because we have uncovered new pathways that lead to the disease, and we know that they truly make a difference.”

    The CUIMC Newsroom spoke with Small about the current state of research into Alzheimer’s treatments and prevention.

    Q: First, the bad news. Why have all drugs tested in the past several years failed?

    In retrospect, the idea that reducing amyloid in the brain—which all the failed drugs do—is based on an incomplete picture of the disease.

    To treat a disease, we need to treat what’s broken. But it’s very difficult to find what’s broken in these slowly progressive brain disorders.

    One way to find what’s broken is through genetics, but the first wave of genetic studies in the 80s and 90s only had the technical capabilities to investigate Alzheimer’s cases that run in families, those caused by a single gene.

    The results of these studies all seemed to converge on one biological process: amyloid.

    But these single-gene forms of Alzheimer’s are rare—and account for maybe 2% to 3% of cases. Most cases of Alzheimer’s are caused by a complex interplay of many genes and the environment.

    The field made the assumption that amyloid is the primary culprit in all forms of Alzheimer’s. It made perfect sense, because we see amyloid in all patients with Alzheimer’s, whether their disease is caused by a single gene or not. The amyloid finding was extremely exciting, and there was a sense that we were on the cusp of curing this devastating, horrible disease.

    Q: Does that mean the amyloid hypothesis is completely wrong?

    The amyloid hypothesis is that amyloid is the trigger of everything in Alzheimer’s. That seems now to be wrong.

    New studies from the past decade tell us that amyloid is part of the story of Alzheimer’s disease, but it’s the smoke, not the fire. We’ve learned that the single-gene and more common, complex forms of Alzheimer’s are not identical, though they do overlap.

    There’s been a lot of backlash against the amyloid hypothesis lately, but in the 90s, it was the right idea. The pharmaceutical industry was right to jump on the amyloid bandwagon. And they’re now right to give it up, I think.

    Q: If drugs against amyloid aren’t the answer, what is?

    Back in the 80s and 90s, genetic tools weren't quite developed enough to address the real question we had: What genes are involved in most cases of Alzheimer’s disease?

    Techniques have advanced and we can now answer this question. New studies—many led by Richard Mayeux, MD [chair of neurology at Columbia]—have been pointing to other processes in the brain. We also have better biological tools that can reveal the basic problem inside neurons.

    Based on this research, the new consensus in the field is that there are two other pathways that cause the disease.

    One involves “protein trafficking,” which is how proteins are shipped to different sites within a single cell. The health of neurons, more so than other cells, depends on protein trafficking in and out of one particular site: the endosome.

    In Alzheimer’s, the flow of proteins out of the endosome is blocked, and we think that causes the other problems we see in the disease: the amyloid, the tau tangles also common in the Alzheimer’s brain, and the neurodegeneration. Essentially it's a plumbing problem.

    Our research here at Columbia provided some early evidence for an endosomal trafficking problem in Alzheimer’s. And genetic studies—including those led by Dr. Mayeux—have now found that some endosomal genes are linked to Alzheimer’s, which provides more support.

    The second pathway involves microglia, which are cells in the brain that help maintain the health of neurons and help keep the spaces between neurons clear of pathogens, protein aggregates, and other cellular debris.

    Recently discovered genes—by Phil De Jager, MD, PhD, in our center and others—point us to these cells. But what exactly is wrong with the microglia is still hotly debated. We don’t know if they’re working too well or not well enough, but we do know they’re not working properly.

    Q: What makes you so optimistic that we will find a treatment that slows or stops the disease?

    We now, I believe, have evidence to help us understand why the first hypothesis was wrong. Scientifically, we have very good justification to argue why our new hypotheses are correct.

    We’re now seeing that companies are getting back into drug development because these new pathways are so compelling.

    In the coming years, our biggest focus at the Alzheimer’s Disease Research Center at Columbia will be accelerating drug discovery. One of the most important goals is to develop new biomarkers—for the new Alzheimer’s pathways. These biomarkers are crucial for developing the new generation of therapeutic agents. These biomarkers will be useful for enrolling patients into new anticipated clinical trials, following the logic of precision medicine. Also, just as biomarkers of amyloid were important for testing assumptions about the primacy of amyloid in the disease, these biomarkers are important for testing—or potentially refuting—the new pathways.

    We’re also testing gene therapies and other ways to restore endosomal trafficking to see if that prevents neurodegeneration in animal models.

    Frank Provenzano and Adam Brickman are developing new techniques, with imaging and cognitive testing, to detect patients with endosomal defects as early as possible. We think the sooner we can treat people, the better. Sabrina Simoes, one of our newest members, is developing new ways to use spinal fluid and blood to remotely monitor endosomal trafficking. That’s a critical step in measuring a drug’s effectiveness when the drug moves to clinical testing.

    In science, though, you never can be sure. The only way we’ll know we’re right is by developing drugs and testing the hypothesis in clinical trials in patients, like we did with the amyloid hypothesis.

    Q: Is there anything people can do now to prevent the disease, or at least delay it for several years?

    In my practice, I encounter many people who have family members with Alzheimer's and they’re worried about their genes. But in most cases, just because your mother has it doesn’t mean you’re going to get it.

    In a complex disease, each gene and each environmental factor is like putting a pebble on a scale. None of them by themselves can prevent or cause Alzheimer’s. So if your parent has Alzheimer’s, that puts one pebble on the scale. But if you went to college, if you exercise, those are pebbles on the other side of the scale. Many of the things that we thought historically cause Alzheimer's have been debunked—for example, the idea that it was caused by various heavy metals. But we do know that maintaining cardiac health is good: Exercise is good; smoking is bad; developing diabetes or obesity increases the risk. These recommendations, as most people know, are true for any disease.

    People often ask me this question, hoping I know something that no one else does. I don’t have any other answers at the moment, but everyone in the field is doing their best to find new ways to forestall this disease.

    The Association of Clinical Research Professionals (ACRP) has selected NeuroNEXT Project Manager Joyce Moran from our Columbia University Irving Medical Center and Weill Cornell Medical College clinical sites to become a Fellow of the ACRP (FACRP). This FACRP designation represents a global mark of distinction for Joyce: each year, only a handful of clinical research professionals are selected worldwide! This honor recognizes Joyce for her many substantial contributions to the field and designates her a ‘global leader in clinical research.’ Please join in congratulating Joyce on this well-deserved honor!

    November 17, 2019
    By Anne Tergesen
    What Science Tells Us about Preventing Dementia

    In another population study, researchers at Columbia University analyzed data from 593 people age 60 or older, 106 of whom developed dementia. People with clerical, unskilled or semiskilled jobs had greater risk of getting the disease than managers and professionals. … Yaakov Stern, a professor at Columbia University College of Physicians and Surgeons who has written about these studies and the impact of education on dementia, recommends maintaining “educational and mentally stimulating activities throughout life.” [read more]
    November 13, 2019
    By Gary Stix
    Literacy Might Shield the Brain from Dementia

    An ability to read and write, even with little or no schooling, could offer protection.

    Socrates famously railed against the evils of writing. The sage warned that it would “introduce forgetfulness into the soul of those who learn it: they will not practice using their memory because they will put their trust in writing.”

    He got a few things wrong. For one, people nurture Socrates’ memory because of all of the books written about him. But he also was off the mark in his musings about a forgetfulness of the soul. If anything, it appears that just the opposite holds: a study of hundreds of illiterate people living at the northern end of an island considered to be a world media capital roundly contradicts the father of Western philosophy.

    Evaluations of the elderly in the environs of Manhattan’s Washington Heights (the neighborhood immortalized by a Lin-Manuel Miranda musical) reveal that the very act of reading or writing—largely apart from any formal education—may help protect against the forgetfulness of dementia. “The people who were illiterate in the study developed dementia at an earlier age than people who were literate in the study,” says Jennifer J. Manly, senior author of the paper, which appeared on November 13 in Neurology.

    Earlier studies trying to parse this topic had not been able to disentangle the role of reading and writing from schooling to determine whether literacy, by itself, could be a pivotal factor safeguarding people against dementia later in life. The researchers conducting the new study, who are mostly at Columbia University’s Vagelos College of Physicians and Surgeons, recruited 983 people with four years or less of schooling who were part of the renowned Washington Heights–Inwood Columbia Community Aging Project. Of that group, 238 were illiterate, which was determined by asking the participants point-blank, “Did you ever learn to read or write?”—followed by reading tests administered to a subsample. Even without much time in school, study subjects sometimes learned from other family members.

    The average age of the illiterate group was about 78, and many had come from rural parts of the Dominican Republic, which had experienced the legacy of midcentury strongman Rafael Trujillo’s educational neglect. Smug assumptions cannot be made about universal literacy: the Department of Education estimates there are 32 million adults in the U.S. who are illiterate.

    In the Washington Heights study, 35 percent of the illiterate group (82 of 238) had dementia when the study began, as against 18 percent (137 of 743) of literate participants. Multiple follow-ups occurred: the average interval was four years, and data were gathered as far back as 23 years. Of the 155 illiterate people who did not have dementia when first examined, 48 percent were diagnosed with it upon follow-up, whereas 27 percent of the 609 such individuals in the literate group were no longer dementia-free.

    The researchers found that literacy was linked to higher scores on cognitive measures not solely tied to reading or language skills. And other research has discovered more gray matter and other beneficial changes in the literate brain. Separately, it surprised the new study’s team that the rate of cognitive decline did not differ between the literate and illiterate groups—perhaps because the illiterate segment, when first examined, was already closer to meeting dementia thresholds. Also, the dementia risk posed by illiteracy was the same for men and women, unlike in some earlier investigations that tilted toward a higher peril for women.

    Heather M. Snyder, vice president of medical and scientific relations at the Alzheimer’s Association, says this study will add to the literature on “life-course contributions” as a means to diminish dementia risk, adding that factors other than literacy must be taken into account. “I think it will be really important to take this study, which is a nicely done study in a large number of individuals, and really understand what are some of the other factors that might be at play for these individuals,” she says.

    The paper raises an obvious idea for future research: “Could we change and lower that dementia risk by intervening at midlife or later life by helping people to learn to read and write?” says Miguel Arce Rentería, the first author of the study. “That’s an empirical question.”

    The benefits of pushing forward become immediately obvious when contemplating what, exactly, is going on when a person processes words. In her book Proust and the Squid: The Story and Science of the Reading Brain, cognitive scientist Maryanne Wolf writes that learning to read entails “an amazing panoply of phonological, semantic, syntactic, morphological, pragmatic, conceptual, social, affective, articulatory, and motor systems, and the ability of these systems to become integrated and synchronized into increasingly fluent comprehension.” Forget brain games—just read a good book.

    Also covered by: The New York Times

    November 13, 2019
    By Alan Mozes
    HealthDay Reporter
    November 19, 2019
    People Who Can't Read Face 2-3 Times Higher Dementia Risk

    Could illiteracy up your odds for dementia?

    That's the suggestion of a study that found seniors who couldn't read or write were two to three times more likely to develop dementia than those who could.

    The finding "provides strong evidence for a link between illiteracy and dementia risk," said study author Jennifer Manly, a professor of neuropsychology at Columbia University's College of Physicians and Surgeons in New York City.

    The finding also offers sobering insight into how dementia risk could be disproportionately affecting the roughly 32 million illiterate adults in the United States.

    For the study, Manly and her colleagues focused on men and women who were at least 65, with an average age of 77. Most had been born and raised in rural areas of the Dominican Republic before moving to northern Manhattan. None -- including those who could read or write -- had gone to school for more than four years.

    Three separate groups of participants were tracked for an average of about four years, with the first group formed in 1992, followed by a second in 1999 and a third in 2009, for a total of 983 people. For each group, medical exams were conducted every 18 to 24 months, as were screenings that assessed thinking, language, memory and visual-spatial skills.

    Among those who were illiterate, over a third (35%) already had dementia when the study was launched.

    By comparison, just 18% of literate participants had dementia when the investigation began. And after taking into account key factors -- such as age, income and heart disease history -- the team concluded that those who were illiterate were three times more likely to have already developed dementia at the beginning of the investigation.

    The team also found that after a four-year follow-up, 48% of the illiterate group eventually developed dementia.

    But among the literate group, just 27% went on to develop telltale memory and thinking problems.

    The team concluded that, all things being equal, those who were illiterate were twice as likely to develop dementia during the study.

    So, what is it about reading and writing that seems to protect against dementia?

    Manly cautioned that the study does not definitively prove that illiteracy causes dementia risk to rise. And she stressed that extenuating circumstances -- such as why someone may never have learned to read or write in the first place -- may also have a bearing on long-term dementia risk.

    Still, "having had the opportunity to learn to read and write may have lifelong advantages, compared to people who did not have the opportunity to learn these skills," Manly theorized.

    "Being able to read and write allows people to engage more often in what we could call 'cognitively enriching' activities," she said. "In other words, activities that 'exercise' the brain, like reading newspapers and books, helping children and grandchildren with their homework, or getting a job that requires literacy. Learning to read and write allows a person to participate in these activities all throughout their lifetime."

    With that in mind, Manly and her colleagues said researchers should now explore whether or not tackling illiteracy might be a way to lower dementia risk.

    But Heather Snyder, vice president of medical science relations for the Alzheimer's Association, cautioned that "literacy is shaped by a number of factors, and it is important that all of these factors be better understood and explored as potential contributors to dementia risk."

    Nevertheless, Snyder, who wasn't involved with the research, said the "results of this study are interesting, and add to the body of knowledge that supports the idea that there are many elements that contribute to later life risk of cognitive decline."

    The study, published Nov. 13 in the journal Neurology, was sponsored in part by the U.S. National Institutes of Health and the U.S. National Institute on Aging.
  • UPI
    November 7, 2019
    By HealthDay News
    Education buffers genetic risk for Alzheimer's among black people

    Higher levels of education may counter the genetic risk of Alzheimer's disease among older black adults, a new study indicates.

    "This suggests that education can buffer the effects of the APOE e4 gene on episodic memory retention and working memory, which are usually the first types of memory to be affected in people with Alzheimer's," said study first author Jet Vonk. She is a postdoctoral research scientist at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University, in New York City.

    Several studies, mainly in white people, have shown that the higher a person's level of education, the lower their risk of dementia, even among those who are genetically at higher risk. But none of those studies have looked at black Americans, a group with fewer years of education, greater prevalence of the APOE e4 gene, and higher rates of dementia than whites, the researchers noted.

    The new study included 849 black people, average age 69, with various educational levels. None of the them had dementia, but about 38 percent had the APOE e4 gene, the biggest genetic risk factor for late-onset Alzheimer's disease.

    Even before Alzheimer's is diagnosed, older people with the APOE e4 gene tend to have poorer brain function than those without it, according to the researchers.

    The participants in this study underwent memory and thinking ("cognitive") tests. Among those with more than a high school diploma, APOE e4 carriers did just as well on two key memory tests as non-carriers, and this was particularly evident in women.

    The study was published online recently in the Journal of Alzheimer's Disease.

    "There's frustratingly little we can do to lessen the risk of Alzheimer's disease, but education appears to be one of the few interventions that we know works," Vonk said.

    The findings suggest a way to reduce rates of Alzheimer's and other types of dementia.

    "The important point is that education is a modifiable risk factor for cognitive decline. It's something that we can target with public policies that increase access to higher education," Vonk said.

    "There's frustratingly little we can do to lessen the risk of Alzheimer's disease, but education appears to be one of the few interventions that we know works," Vonk said. The findings suggest a way to reduce rates of Alzheimer's and other types of dementia. "The important point is that education is a modifiable risk factor for cognitive decline. It's something that we can target with public policies that increase access to higher education," Vonk said.
  • SELF
    October 25, 2019
    8 Things To Know About Frontotemporal Degeneration
    It's a form of dementia that typically affects younger adults.

    When you hear the word “dementia,” what comes to mind? For most people, probably an image of someone in their 70s or 80s who is suffering from debilitating memory problems. But there is another form of dementia that you’ve probably never heard of: frontotemporal degeneration (FTD), also called frontotemporal dementia or frontotemporal lobar degeneration (FTLD).

    “It’s very different from the idea people have in their minds of what dementia is,” Edward D. Huey, M.D., associate professor of psychiatry and Neurology at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center and member of the Medical Advisory Council for The Association for Frontotemporal Degeneration (AFTD), tells SELF.

    That’s why it’s especially important to be aware of what FTD is and how it can present. Just this week, the AFTD hosted its annual Hope Rising Benefit, raising over $2 million to support patients and caregivers in the community and fund research. Here’s what you should understand about this little-known health issue.

    1. FTD refers to a group of brain disorders that cause dementia.

    Dementia is a serious loss of cognitive abilities that interferes with a person’s capacity for functioning on a daily basis, the National Institute of Neurological Disorders and Stroke (NINDS) explains.

    Alzheimer’s is the leading cause of dementia, and it’s also the one most of us know about. But up to 10 percent of all cases of dementia may be caused by FTD, which is actually the umbrella term for a group of different brain diseases. FTD is thought to affect between four to 15 out of every 100,000 people in the United States, according to the AFTD.

    FTD occurs when neurons in the frontal and temporal lobes of the brain die, causing these parts of the brain to atrophy or shrink. This prompts problems with the thought processes and behavior controlled by these lobes, according to the NINDS.

    2. FTD is the most common form of dementia in younger people.

    According to the NINDS, FTD is the number one cause of dementia in people under age 60. (It seems to affect men and women in equal numbers.) About 60 percent of people with FTD are between the ages 45 and 64, the NINDS says. “FTD basically peaks in middle age,” Dr. Huey says, “as opposed to Alzheimer’s, where your chances of getting it go up as you get older.” However, FTD onset can start as early as someone’s 30s or as late as their 90s, according to the NINDS—so it really spans the age spectrum in that sense.

    3. The most common form of FTD causes changes in behavior and personality.

    While Alzheimer’s primarily affects memory, that’s not the case with FTD. The most common kind of FTD is called behavioral variant frontotemporal dementia (bvFTD), per the National Institute on Aging (NIA). “The most common thing I hear is, ‘This is just not my husband, this is just not their personality,’” Dr. Huey says. “People start doing things that are out of character.”

    The result is a long, varied list of potential symptoms related to behavioral changes, according to the NINDS, like apathy, distractibility, repetitive or compulsive behavior, decreased energy and motivation, changes in food preferences, increased interest in sex, neglect of personal hygiene, and feelings of agitation or emotional blunting. FTD patients may also experience a lack of empathy, a lack of social tact, loss of insight into themselves and others, and disinterest in people they used to care about. For instance, “Someone might lose all interest [in] seeing their new grandchild,” Dr. Huey says. “And their interactions with people become kind of bizarre—they talk too loud, talk too soft, stand too close, stand too far.”

    Less commonly, people with bvFTD show symptoms involving language disturbances. People can find it difficult to speak and understand others, and this can occur separately or in conjunction with the behavioral symptoms, according to the NINDS. While estimates vary, Dr. Huey says about 25 percent of patients present with this variety.

    4. FTD can be extremely difficult to diagnose for several reasons.

    First, many of the symptoms don’t seem medical in nature. “These are not symptoms where you would automatically recognize, ‘We need to go to a doctor because there's a medical problem,’” Susan Dickinson, CEO of the AFTD, tells SELF. And the sheer variety of symptoms means there is not really a classic presentation. There’s also no one single test doctors can use to diagnose the illness, the Mayo Clinic says. Instead, they may need to rely on a battery of exams, such as memory testing and brain scans.

    Another huge issue is that the person with FTD is unlikely to recognize these changes in themselves and go to a doctor. “The behavioral variant almost always impairs awareness [in the patient], so they don’t think anything’s wrong and they don’t seek evaluation,” Dr. Huey explains. “So most patients we see, it’s the families [bringing] them in.”

    Even when someone is brought to the doctor, physicians may lack awareness of the condition, Dr. Huey says. Since some of these symptoms can also occur with other conditions that are much better known, people are often misdiagnosed. “A lot of patients get misdiagnosed with a psychiatric disorder, often depression,” Dr. Huey says. “It can be a really arduous journey for families of going to 10, 20 different specialists before you get somebody who will really listen and who knows about FTD and who can connect the dots,” Dickinson adds.

    5. The cause of FTD is unknown, but there is a strong genetic component.

    We don’t know what causes the majority of FTD cases. But about 15 to 40 percent of cases can be linked to a genetic cause, and people with a family history of FTD are more likely to have it, according to the NINDS. In fact, a family history of FTD is the only known risk factor, the Mayo Clinic explains.

    Scientists have identified several different genes in which a mutation can lead to FTD. Some of these genes are also linked to the motor neuron degenerative disease ALS (amyotrophic lateral sclerosis), which is why the two often co-occur, per the NINDS.

    6. There is currently no treatment for FTD.

    One of the worst things about FTD is that it progresses steadily and often quickly. We don’t have treatments to prevent, slow down, or cure FTD, according to the NINDS. Treatments like antidepressants can help manage symptoms by reducing behavioral problems, the Mayo Clinic notes, but that’s more of a stopgap in the absence of better options.

    Usually, managing the disease requires a team of specialists—such as speech, physical, and occupational therapists—to provide support, address various symptoms, and improve quality of life for both the patient and their caregivers, the NINDS explains. In its end stages (which can arrive in as little as less than two years or take longer than 10), the disease starts looking similar to the end stages of Alzheimer’s, where the person loses the ability to perform the basic functions they need to survive, like eat, drink, or move. The patient often requires 24-hour care and is at a much higher risk of potentially life-threatening complications like pneumonia.

    7. FTD can be incredibly hard on families.

    “When you're dealing with a rare disease like this, one of the most definitive features is how isolating it is for the people living with it every day,” Dickinson says. “Often, caregivers and spouses will say one of the hardest things is that they’ve lost their loved one. [That individual] isn’t there for you, and they’re not your partner in this process,” Dr. Huey adds.

    That’s why one of the AFTD’s primary purposes is “to create a community where people who are diagnosed and their families feel understood and less isolated,” Dickinson says. To that end, the AFTD offers 100 support groups in 32 states, a wealth of online resources, a toll-free helpline (1-866-507-7222), and various online and Facebook support groups. “Just finding a place where people understand what you’re going through is a huge help. People can share their experiences and challenges, learn strategies that are helpful from each other, and find professional supportive services [and resources],” Dickinson says.

    The AFTD also hosts conferences and connects people without support groups in their area to one another. “We might know of three other people who do live near you who are in the same boat,” Dickinson says. “So we can connect caregivers one-on-one to be a friend to listen and understand and maybe provide some guidance.”

    8. Research and awareness are gaining momentum.

    Most people haven’t heard of FTD, which is why it’s important to spread the word so that families and doctors alike are better able to recognize the condition it when they see it, Dickinson says.

    The good news here: “I think FTD has more awareness in the funding and research world than in the general public,” Dr. Huey says.

    “There are several very promising avenues of research right now,” Dr. Huey says. “We’re learning a lot.” For example, a group of academic medical centers in the United States and Canada called Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) is currently seeking volunteers for a longitudinal study that will collect clinical and genetic data from patients and their families to help us learn more about the disease.

    One huge research priority is identifying biomarkers and neuropsychological screening tools to help diagnose people with greater accuracy and speed, per the National Institutes of Health. Dr. Huey is particularly excited about the strides being made to develop treatments targeted at specific genetic abnormalities. He says these experimental treatments will probably start to enter clinical trials in the next few years. And because of the overlaps between FTD and other forms of dementia like Alzheimer’s, Dr. Huey is hopeful that advances in diagnosis and treatment for one condition may translate to the other.

    With all of these efforts, “We’re really working towards a more hopeful future for families facing this truly devastating disease,” Dickinson says. “One where there are drugs, there is a diagnosis, and there is a broader awareness and understanding in society that not all dementia is Alzheimer’s.”
  • TIME
    June 26, 2019
    By Alice Park
    Despite the Headlines, We Don't Yet Know If Anticholinergic Drugs Contribute to Dementia Risk

    There are a number of things that can increase the risk of dementia: age, of course, as well as certain genetic profiles and behaviors such as smoking and drinking. Some of the same things that contribute to heart disease, such as high cholesterol levels and the build up of plaques in the blood vessels, can also boost the chances of developing dementia.

    And in a large study published in JAMA Internal Medicine (link is external) conducted in the UK, researchers report another possible factor: a group of drugs known as anticholinergics. These include prescription medications for treating depression, pulmonary disease, and Parkinson’s, as well as over-the-counter remedies for allergies. British researchers analyzed data from nearly 59,000 people with dementia as well as people without the condition and found that those who took the most anticholinergic drugs were 49% more likely to have developed dementia compared to those not taking the medications.

    Anticholinergic drugs work by blocking a brain chemical called acetylcholine, which is critical for regulating muscles and for controlling messages sent to the nervous system. Previous studies have found side effects including memory loss and confusion linked to the drugs, so the British team wanted to investigate how these medicines might connect to dementia risk.

    While the results are intriguing, they do not suggest that the medications are a definite risk factor for dementia. For one, the study was designed to detect only an association, and not a cause-and-effect relationship, between the drugs and dementia. Second, notes Yian Gu, an assistant professor in neurological sciences at Columbia University who was not involved in the study, the researchers could not fully discount the possibility that whatever condition prompted the patients to take the medications in the first place was actually connected to heightened dementia risk, and not the drugs themselves. For example, depression and sleep disturbances, two reasons anticholinergic drugs are prescribed, are often a precursor to Alzheimer's dementia.

    “This is a very large study and seems to be well designed,” says Keith Fargo, director of scientific programs and outreach at the Alzheimer's Association, “but the issue for this kind of study is that no matter how well you design it, it’s impossible to control completely for all possible confounding variables.”

    To truly see if anticholinergic drugs are contributing to dementia risk, researchers would have to take a group of people on the medications, ask them to stop taking them, and then compare their rates of dementia to those who continued to take them, to see if there were any differences.

    That's unlikely to happen, since the drugs are effective in addressing symptoms for many patients. For now, says Fargo, people who are on the medications should not stop taking them, and the findings, while interesting, aren’t likely to change the way doctors prescribe the drugs—at least until more research is done to clarify if, and how they might be influencing dementia risk. “I don't think we’ll see people changing practice guidelines at this point, and people will likely still err on the side of treating conditions as effective as possible with these medications, rather than going all out to avoid them. It’s just too early to be doing that.”

    June 19, 2019
    By Robin Seaton Jefferson
    Scientists Seek To Discover Why Some Minds Resist The Damage That Comes With Old Age

    Researchers at the National Institute on Aging (NIA) want to know how some older adults retain their youthful thinking and memory abilities despite the evidence of neurodegeneration or Alzheimer’s-related pathology in the brain. And they’ve created a way they hope will help them find out. But they need the input of scientists, health care professionals and others to do it.

    It's called cognitive reserve, and it's the phenomenon of the mind's resistance to damage of the brain. It's also the subject of not only an upcoming new data and biomedical sample resource, but also a related request for information (RFI) from the NIA and a first-of-its-kind workshop in September.

    The push to study cognitive reserve in more depth across the scientific disciplines was born out of recommendations from the Cognitive Aging Summit III. Some 300 researchers attended the summit in Bethesda, Maryland in 2017. Coordinated by the NIA of the National Institutes of Health (NIH) and supported by the McKnight Brain Research Foundation, the summit centered on age-related brain and cognitive changes, with a particular focus on issues related to cognitive resilience and reserve. According to the NIA, investigators from around the world delivered presentations and engaged in discussion “about some of the most important scientific questions relating to the biological, physiological, social and behavioral aspects of reserve and resilience in aging individuals. Attendees also discussed strategies to preserve and bolster cognitive function during aging.”

    One of the ways they decided to pursue studying how to preserve and bolster the brain during aging was to support a life-long study of rats. Investigators recommended the study generate state-of-the-art neuroimaging, phenotypic results (the observable characteristics of an individual resulting from the interaction of its genotype with the environment), non-invasive biological samples and other indicators that could give insight into the mechanisms of healthy neurocognitive aging. Researchers at the NIA said this recommendation is now being put into action.

    They’re calling it the Successful Trajectories of Aging: Reserve and Resilience in RatS, or STARRS. The NIA’s Intramural Research Programs (IRP) will develop and conduct the longitudinal study, thus creating an open-source data and a sample hub to be shared with the entire aging science community.

    According to Peter Rapp, senior investigator in the Neurocognitive Aging Section (NAS) of the NIA, “cognitive reserve is what makes some older adults cognitively resilient.” And reserve and resilience make up “an evolving field exploring whether and how people with high cognitive reserve simply age more slowly than their peers whose thinking and memory are impacted by neuropathology, or if there are genetic, environmental or life experience protective factors at work. NIA-supported scientists aim to study reserve at the cellular level and establish baseline data to evaluate how various interventions might impact brain aging and the ability to compensate for dementia pathology."

    Rapp said scientists hope STARRS will bring them “closer to an understanding of the factors that contribute to successful versus unsuccessful neurocognitive aging.”

    The NIA, today, issued a Request for Information for new ideas on how best to maximize STARRS’s value and usefulness to the scientific community. The RFI seeks input from researchers in academia and industry; healthcare professionals; patient and health advocacy organizations; scientific and professional organizations; and other interested stakeholders on a wide variety of program design issues, including:

    • Prioritizing which data outcomes/measures to capture.
    • Suggestions for non-invasive methods to assess neural function in study animals.
    • Creative ideas for the STARRS infrastructure to help it better track behavioral and/or neural function.

    Responses to the RFI are due by July 15, 2019. Those who wish to contribute may email their responses to Dr. Matthew Sutterer at the NIA.

    The concept of cognitive reserve is not new. Dr. Yaakov Stern of the Cognitive Neuroscience Division of the Taub Institute, the Department of Neurology and the Department of Psychiatry, at Columbia University, wrote of his own studies of the subject in 2009:

    “The concept of reserve has been proposed to account for the disjunction between the degree of brain damage or pathology and its clinical manifestations,” he wrote. “For example, a head injury of the same magnitude can result in different levels of cognitive impairment, and that impairment can vary in its rate of recovery. Similarly, several prospective studies of aging have reported that up to 25% of elders whose neuropsychological testing is unimpaired prior to death meet full pathologic criteria for Alzheimer's disease, suggesting that this degree of pathology does not invariably result in clinical dementia…many studies indicate that a set of life experiences such as educational and occupational exposure and leisure activities are associated with reduced risk of developing dementia and with a slower rate of memory decline in normal aging. Cognitive reserve (CR) postulates that individual differences in the cognitive processes or neural networks underlying task performance allow some people to cope better than others with brain damage.”

    Professor Michael Ridding of the School of Medicine at the University of Adelaide in South Australia also wrote in an article for The Conversation that “Evidence shows the extent of someone’s cognitive decline doesn’t occur in line with the amount of biological damage in their brain as it ages. Rather, certain life experiences determine someone’s cognitive reserve and, therefore, their ability to avoid dementia or memory loss.”

    “How do we know?” Ridding asked. “Being educated, having higher levels of social interaction or working in cognitively demanding occupations (managerial or professional roles, for instance) increases resilience to cognitive decline and dementia. Many studies have shown this. These studies followed people over a number of years and looked for signs of them developing cognitive decline or dementia in that period.”

    In 2009, the Human Sensorimotor Plasticity group headed by Ridding and the Developmental Neuromotor Physiology group headed by Dr. Julia Pitcher joined the Robinson Institute and formed the Neuromotor Plasticity and Development (NeuroPAD) research group. Riding is known for his pioneering work in human brain plasticity induction.

    The design of STARRRS will also be among the topics discussed at the upcoming Reserve & Resilience Workshop—the first workshop on researcher definitions for reserve and resilience in cognitive aging and dementia—to be held September 9 and 10, 2019 in Bethesda, Maryland. Organizers of Reserve & Resilience, such as Workshop Chair Dr. Yaakov Stern of Columbia University, aim to attract researchers from diverse backgrounds to move the cognitive reserve and resilience field forward by delving into some of the following:

    • Reaching a consensus on operational definitions of reserve and resilience.
    • Developing interdisciplinary research collaboration strategies.
    • Identifying promising research themes for pilot study funding.
    • Developing data and information sharing platforms for collaborative analysis.
    • Establishing workgroups that will meet throughout the year to further the aims of the workshop.

    According to organizers of the workshop:

    “Research indicates that specific life exposures and genetic factors contribute to some people being more resilient than others, with lower rates of cognitive decline with aging and reduced risk of developing Alzheimer’s disease and related dementia (ADRD). The factors associated with resilience have an important role in the development of interventions and health policies. There are likely several complex and highly interactive mechanisms that lead to these individual differences in vulnerability to decline, probably reliant on both structural and functional brain mechanisms. Investigators in this area have employed many terms encapsulating individual differences including resilience, cognitive reserve, brain reserve, brain maintenance and compensation. In addition, there are terms commonly used in cognitive neuroscience studies of aging, such as efficiency, capacity, and compensation. However, the definitions of these concepts differ across researchers, and the translation from human to animal research is not well developed. It is important to bring together researchers from basic neuroscience to human studies to develop operational definitions for these concepts.”
    April 30, 2019
    Bringing Physicians Up to Speed on Precision Medicine

    Precision medicine has arrived, but many physicians do not have the training or time to incorporate genetic sequencing technologies into everyday practice. In two articles published online in the Annals of Internal Medicine, precision medicine experts at Columbia University Vagelos College of Physicians and Surgeons describe different genetic sequencing techniques and how they may be used to enhance patient care and improve human health. The articles are the first in a series by Columbia experts that will appear in the journal.

    Over the past century, medicine has gravitated away from developing treatment strategies based on individual case reports and a physician's personal experience. Increasingly, physicians rely on evidence-based medicine, which uses data from randomized clinical trials to inform treatment decisions. But because this approach often relies on large data sets, the results highlight what works best on average, while neglecting the underlying genetic differences that trigger disease and affect response to treatment at the individual level.

    Precision medicine, which uses genetic sequencing techniques to look at the underlying genetic causes of disease, may be a solution to this blind spot. But new and sophisticated technologies, combined with the complexities of interpreting genetic data, present significant challenges to many physicians. This precision medicine series is designed to help clinicians understand the basics of sequencing, interpret genetic data, and navigate ethical, legal, and privacy issues.

    In an editorial published in the issue, Lee Goldman, MD, dean of the Faculties of Health Sciences and Medicine and chief executive of Columbia University Irving Medical Center (CUIMC), and Jill Goldman, MS, MPhil, a genetic counselor at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at CUIMC, wrote: "As medical care has evolved from ‘in my experience’ to ‘evidence-based’ to ‘personalized/precision,’ unprecedented opportunities have arisen. We hope [this series] will help practicing physicians understand where we are, what is needed, and why the future is so exciting."

    One article, by Krzysztof Kiryluk, MD, and colleagues, focuses on the use of precision medicine in internal medicine and describes how to interpret genetic data from diagnostic tests, exome sequencing, and genome sequencing.

    Another article, by Wendy Chung, MD, PhD, and colleagues, highlights the widespread availability of direct-to-consumer genetic tests like 23 and Me and the challenges physicians face when patients—who may not be aware of the limitations of the tests—bring their results to their doctor’s appointment and ask questions about their risk for developing various diseases.

    The articles also discuss the limitations of precision medicine. "Widespread application of precision medicine will depend on having patients trust it, physicians adopt it, and insurance companies pay for it," said John Rowe, MD, a co-author of one of the papers.

  • JAMA
    April 24, 2019
    By Rebecca Voelker
    The Arts Dispel Medical Students’ Qualms About Dementia

    Maybe never before had a rendition of "Take Me Out to the Ball Game" had more meaning for Alyssa Vigliotti. As a first-year student at the Penn State College of Medicine, she launched a research project to evaluate whether a creative storytelling program had benefits for people with dementia. Called TimeSlips, the program uses pictures that prompt participants to create stories about the image.

    Or, in this case, break into song.

    Vigliotti said one of her favorite moments during the 6 months she collected data was watching people in the program—all with mild to moderate or severe dementia living in a rural Pennsylvania retirement community—react to a picture of a young boy at a baseball stadium. "Randomly, out of the blue, some of the residents started singing…and it was just such a cool experience," she recalled.

    It was one of many moments in which the residents, some who had been rather withdrawn, began to reminisce, concoct new stories, or simply smile. "That’s what made it so exciting and impactful on me," she added.

    Vigliotti’s study reported no significant changes in dementia severity, but it demonstrated some benefits in quality-of-life measures such as interactions with other residents and expressing pleasure. Observing the program "showed me these are real people who still have real thoughts and real memories and can communicate, just in a different way," she said.

    Vigliotti isn’t the only medical student to have had that reaction. Research also shows that TimeSlips and other nonclinical arts-centered programs in medical school curricula can improve students’ attitudes about dementia.

    Tackling an Important Issue

    As the number of people diagnosed with dementia increases and the search for effective treatments appears stymied, experts said that addressing future physicians’ attitudes has become more pressing.

    "[T]here’s been a 99% fail rate with drugs in the field," said Daniel George, PhD, a Penn State College of Medicine assistant professor who teaches fourth-year medical students how to conduct TimeSlips sessions. "[T]hat gives us an imperative to think creatively and think in different ways about what it means to care for people with memory loss."

    George said students have told him they feared that they wouldn’t be able to connect with people who have dementia and that it would be challenging to work with them. Students also worried that they would say the wrong thing or have an epithet shouted at them.

    "They had a whole host of assumptions and fears that they were nursing," George said. However, those fears weren’t realized. Once they got involved with TimeSlips, "I was seeing a dramatic attitude shift in the way my students regarded people with dementia," George said.

    He collected data to validate that observation. His 2013 study in Academic Medicine measured 22 fourth-year medical students’ attitudes toward people with dementia living in a Pennsylvania retirement community. After 8 sessions, students’ scores improved in 19 of 20 items on the Dementia Attitudes Scale (DAS); 12 of the 19 were significant improvements.

    "In almost every case and every student I’ve ever had, [their views] shifted dramatically," George said.

    No Longer a Fly on the Museum Wall

    In 2008, as a behavioral neurology fellow at Columbia University Medical Center in New York City, James Noble, MD, attended programs for people with dementia and their caregivers at the Metropolitan Museum of Art and the Museum of Modern Art.

    "I was curious to understand how art was expressed by those experiencing dementia," and whether that phenomenon could be measured, he recalled. As he observed from the corner of the room, a facilitator told him to join in. "[B]eing a fly on the wall was not an acceptable role," Noble said. "I didn’t forget that moment."

    He was given a seat and a brush. Painting alongside those with dementia and their caregivers "was absolutely revelatory," Noble said. "[T]here were aha moments where a patient would say something quite profound in the reflection of the art they made."

    Two years later, he launched what’s now called Arts & Minds, which runs programs for people with dementia and their caregivers at the Studio Museum in Harlem, the Met, and several other sites. Although they don’t have specific sessions for medical student participation, the programs served as research sites for one of Noble’s students. Hannah Roberts, MD, now a resident physician in the Harvard Radiation Oncology Program, invited 19 of her classmates to participate in the gallery discussions and artwork sessions while she evaluated whether it changed their perceptions of people with dementia.

    Each student in Roberts’ study attended one 90-minute museum program. Using the DAS, Roberts also found significant improvements in how her classmates perceived people with dementia after taking part in the program. “This fits into a paradigm of experiential learning,” Noble said.

    That’s something with which he’s familiar. As a student at the Emory University School of Medicine in Atlanta, Noble attended Alcoholics Anonymous meetings and visited a halfway house for people who were recently discharged from inpatient psychiatric facilities. "We had to write about it—write poems about it—and really reflect on our experiences," he said.

    Today, poetry programs have become more widespread for people with dementia. Can they also affect medical students’ attitudes? To find out, investigators at the Rowan University School of Osteopathic Medicine in Stratford, New Jersey, studied students’ perceptions about dementia after they participated in a poetry workshop with assisted living facility residents.

    After a single 3½-hour program, the investigators found significant improvements in attitudes toward people with dementia among the 11 students who participated. The students said they were surprised at a nonbiomedical approach’s effectiveness and that they were more likely to use the words hope, creativity, and humanness to describe people with dementia.

    In fact, a couple of the students said they could see ways to adapt workshop techniques for patients with dementia that they may treat in the future. "I think that I would be able to do some of that in the office if patients were willing to do it with me," one of the students said after the workshop.

    Failure-Free Art

    In 2007, Elizabeth Lokon, PhD, was working on a graduate degree in gerontological studies at Miami University in Oxford, Ohio. Her thesis devised a program that combined her background in fine arts and education with gerontology—a fruitful trio. “When I finished in 2008, they hired me to design and implement the program” at Miami, said Lokon, the founder and director of Opening Minds Through Art (OMA).

    Through OMA, students and people with dementia work together to produce failure-free art. “Every piece is abstract,” Lokon said. It’s all about the discovery process of creating art rather than an expectation of what the final product should look like. Individuals with dementia determine the aesthetic and students assist by washing brushes or helping with various materials used during the program. “Students are taught how to give autonomy back to the elder,” Lokon noted.

    In a study that used the DAS to evaluate 156 Miami undergraduate students who participated in OMA, Lokon and her colleagues found that their attitudes toward and comfort level with people who have dementia improved significantly after a semester’s worth of weekly meetings.

    Not all the Miami students who participate in OMA are in health-related fields, but Lokon is launching pilot programs at 8 medical schools. While planning the pilots, Lokon searched the medical literature for articles about how medical schools teach students to have empathy and compassion for older adults.

    "They focus on [healthy] older adults because they believe that exposing medical students to people who are frail and sick and have dementia will strengthen their stereotypes and they become more negative toward aging," Lokon said.

    That notion, she added, flies in the face of what she has seen and documented with Miami students. "Our students actually learn a great deal and become more positive," she said.

    Two of the pilot programs are up and running—one at the University of Toledo College of Medicine and Life Sciences and another at the Ohio University Heritage College of Osteopathic Medicine. Lokon has unpublished data showing that among 22 first- and second-year students at Toledo, the overall DAS score and scores on 10 of the 20 items improved significantly after 1 OMA session.

    Afterward, the students wrote about their experiences. One student explained that while it’s necessary to master the scientific concepts of neuronal loss, cortical atrophy, and ventricular changes, it’s also important to understand how disease affects patients’ daily lives. "I was grateful to have the chance to develop my clinical communication skills and learn how to best interact with a dementia patient," the student wrote.

    Another student described working with a woman who was reluctant to participate in the session. Encouraging the woman to join in was "an opportunity to practice patience and compassion toward a patient," the student wrote. A conversation ensued, the woman began to open up, and together they laughed, painted, and chatted.

    "I will always keep this experience close to my heart and will make sure to keep the values that I have learned with me as I continue on my path to becoming a physician," the student concluded.


    Integrating the Arts Into Medical Education

    Medical educators and experts in the arts and humanities have joined forces to help medical students approach clinical practice with greater empathy for patients and enhanced critical thinking. Some schools use medical improv courses to help students think on their feet and build skills in communication, listening, and teamwork. Others offer opportunities to analyze fine art as a way of improving students’ visual diagnostic skills.

    "It’s really fascinating how diverse the programs are," said Lisa Howley, PhD, senior director of strategic initiatives in medical education at the Association of American Medical Colleges (AAMC).

    The AAMC is currently in the second phase of a 3-part initiative that’s taking an in-depth look at the arts in medical school curricula. Launched in 2017, the first phase consisted of focus groups and listening sessions, followed by a forum in which educators, arts professionals, and students strategized ways to integrate the arts and humanities into medical school curricula.

    In the second phase, a research team will spend the next year conducting a scoping review, which examines an issue more broadly than a focused literature review. The team will evaluate how and why arts and humanities programs are being used in medical education. Since the initiative began, Howley said the AAMC has collected a lot of information about programs being conducted in medical schools and teaching hospitals.

    "[T]hese [methods] are being used to teach a whole variety of things, from dementia and empathizing with patients to diagnostic reasoning and image interpretation to observation skills, and clinician well-being and resilience in their own practice—connecting back to their joy in medicine," she said.

    The key for medical education, Howley noted, is finding ways to integrate arts and humanities into the curricula. An example is a Harvard Medical School course in which students draw parallels between their analysis of works at the Museum of Fine Arts, Boston, and diagnostic approaches in medicine.

    Although it’s focusing on medical education, the AAMC also is interested in hearing from physicians who use the arts to improve patient care—either indirectly as artists to circumvent burnout or directly with patients during office visits. Recently, a physician who’s also a photographer relayed a story from his own practice.

    He noticed a patient staring intently at a photograph hanging in the waiting room. When he asked what attracted her to it, she replied that her pain went away when she looked at the photograph. He printed a copy of the photograph and gave it to her to take home.

    It may be a single anecdote,a but it shows "that the arts can be used to facilitate conversations, help better understand the patient’s experience, and connect with the patient in a different way," Howley said.

    By Jason Daley
    May 1, 2019
    Impaired Sense of Smell in the Elderly Is Linked With Risk of Death

    A new study finds older people who score poorly on a sniff test are 46 percent more likely to die over the next 10 years, but researchers don’t know why.

    Sadly, as people age, almost all the senses decline to varying degrees, including sight, hearing and, less obviously, the sense of smell. But in recent years, researchers have found that dramatic declines in olfactory function can be an early sign of dementia or Parkinson's. But a new study shows reduced sense of smell is also linked to an overall increased risk of death.

    Nicola Davis at The Guardian reports that an international team of researchers looked at smell tests taken by more than 2,200 people between the age of 71 and 82 years old in 1999 and 2000 as part of the National Institute on Aging's Health ABC study. Each participant smelled 12 common scents and were asked to choose the smell from a list of four possibilities. The sniffers were then graded as having either good, moderate or poor olfactory function. The health outcomes of these individuals were then followed up for 13 years incluidng yearly phone surveys.

    After compensating for other health factors like age and smoking, the team found that those elderly people with a poor sense of smell had a 46 percent higher chance of dying a decade out from the test than those with a good sense of smell. Even more, the sense of smell was a particularly good predictor of death for those who were in good health at the beginning of the study. Among those with a sniff score rated poor who were in decent shape, the chance of dying by year 10 was 62 percent higher than those with a good score.

    Looking at the causes of mortality for the 1,211 participants who died by year 13 of the study, about 28 percent of the increased risk can be explained by dementia, Parkinson’s disease, and possibly to cardiovascular disease. Respiratory disease and cancer did not appear to be linked to the sense of smell. The research appears in the journal Annals of Internal Medicine.

    That means, points out Stephanie Pappas at LiveScience, that 72 percent of the risk linking impaired senses of smell with death is unexplained.

    "We don't have a reason for more than 70 percent of the increased risk,” study senior author Honglei Chen of Michigan State University says in a press release. “We need to find out what happened to these individuals."

    It’s possible, he says, that a deteriorating sense of smell is an early warning sign for health conditions that are not picked up during routine medical visits. To figure it out, Chen says he hopes to dig even deeper into the data.

    In the meantime, he suggests physicians should start paying attention to olfactory problems. "It tells us that in older adults, impaired sense of smell has broader implications of health beyond what we have already known," he says. "Incorporating a sense of smell screening in routine doctor visits might be a good idea at some point."

    Currently, however, there is no sniff test available for clinical use, and the U.K's National Health Service says there is no "smell test for dementia" on the horizon. In fact, the NHS points out that since this is an observational study, it cannot definitively explain why sense of smell and mortality could be linked.

    Still, some researchers are confident enough in the link between dementia and sense of smell that they are developing scratch and sniff tests to screen for the disease. Columbia University’s Irving Medical Center reports that researchers hypothesize that the olfactory bulb is one of the first parts of the brain to suffer damage from Alzheimer’s and other neurodegenerative disorders. Early, small-scale experiments by neurologist William Kreisl show that a strong sense of smell can often rule out Alzheimer’s, but impaired smell may be related to many diseases, including Parkinson’s, Alzheimer’s and Huntington’s disease.

    The biggest benefit of a smell test if and when it is developed, Kreisl argues, could be flagging those patients who should be referred for more invasive and expensive tests like PET scans.

  • CBS
    May 6, 2019

    Dr. Edward (Ted) Huey was featured on a CBS This Morning segment recently about frontotemporal dementia (FTD), the third most common type of neurodegenerative dementia and the leading cause of dementia in people under age 60. Watch the video.

    January 23, 2019
    By Jocelyn Kaiser
    Gum Disease–Causing Bacteria Could Spur Alzheimer’s

    Poor oral health is a risk factor for Alzheimer’s disease. What’s not clear is whether gum disease causes the disorder or is merely a result—many patients with dementia can’t take care of their teeth, for example. Now, a privately sponsored study has confirmed that the bacteria that cause gum disease are present in the brains of people with Alzheimer’s, not just in their mouths. The study also finds that in mice, the bacteria trigger brain changes typical of the disease.

    The provocative findings are the latest in a wave of research suggesting microbial infections may play a role in Alzheimer’s disease. But even some scientists who champion that once-fringy notion aren’t convinced that Porphyromonas gingivalis, the species fingered in the new study, is behind the disorder. “I'm fully on board with the idea that this microbe could be a contributing factor. I'm much less convinced that [it] causes Alzheimer’s disease,” says neurobiologist Robert Moir of the Harvard University–affiliated Massachusetts General Hospital (MGH) in Boston, whose work suggests the β-amyloid protein that forms plaques in the brains of Alzheimer’s patients is a protective response to microbial invaders.

    The new study, published today in Science Advances, was sponsored by the biotech startup Cortexyme Inc. of South San Francisco, California. Co-founder Stephen Dominy is a psychiatrist who in the 1990s became intrigued by the idea that Alzheimer’s could have an infectious cause. At the time, he was treating people with HIV at the University of California, San Francisco. Some had HIV-related dementia that resolved after they got antiviral drugs. Dominy began a side project looking for P. gingivalis in brain tissue from deceased patients with Alzheimer’s, and—after his work found hints—started the company with entrepreneur Casey Lynch, who had studied Alzheimer’s as a graduate student.

    Working with labs in Europe, the United States, New Zealand, and Australia, the Cortexyme team confirmed earlier reports that P. gingivalis can be found in the brains of deceased people with Alzheimer’s, and they detected the microbe’s DNA in living patients’ spinal fluid. In more than 90% of the more than 50 Alzheimer’s brain samples, they also spotted toxic enzymes produced by the bacteria called gingipains. Brains with more gingipains had higher quantities of the Alzheimer’s-linked proteins tau and ubiquitin. Even the brains of roughly 50 deceased, apparently dementia-free elderly people selected as controls often had lower levels of both gingipains and the proteins indicating Alzheimer’s pathology. That early appearance is important, Lynch says, because “you would expect it to be there before the onset” of symptoms.

    To explore whether the bacteria were causing disease, the team swabbed the gums of healthy mice with P. gingivalis every other day for 6 weeks to establish an infection. They later detected the bacteria in the animals’ brains, along with dying neurons and higher than normal levels of β-amyloid protein. In a lab dish, the gingipains—whose job is to chop up proteins—damaged tau, a regularly occurring brain protein that forms tangles in people with Alzheimer’s. In the brain, this protein damage may spur the formation of tangles, they say.

    Giving the mice a drug that binds gingipains cleared P. gingivalis from the brain better than a common antibiotic, and it reduced the β-amyloid production and resulting neurodegeneration. Targeting gingipains likely works by cutting off nutrients and other molecules that the enzyme supplies to the bacteria, Dominy says. In initial tests with human volunteers, a similar drug seemed safe and showed signs of improving cognition in nine participants with Alzheimer’s, the company says. A larger study is slated to start this year.

    Although the paper refers to “evidence for causation,” Dominy goes a step further and says the experiments suggest “P. gingivalis is causing Alzheimer’s.” He and Lynch note that a study published in PLOS ONE in October 2018 by a team at the University of Illinois in Chicago also found that an oral infection with P. gingivalis can cause amyloid buildup and neurodegeneration in the brains of mice.

    The Cortexyme study is “the largest to date” to find P. gingivalis in Alzheimer’s brains, and it “is clearly very comprehensively approached,” says neurologist James Noble of Columbia University, who has studied the link between periodontal disease and Alzheimer’s. “These are strange ideas, but they seem to be getting some traction.”

    Other pathogens have been found in the brains of people with Alzheimer’s, including spirochete bacteria, which can cause Lyme disease, and some herpesviruses. Moir and Rudolph Tanzi at MGH have shown that β-amyloid in the brain appears to protect mice from bacterial and viral infections by trapping the invaders. Too much of this protective response to pathogens could trigger the buildup of the disease’s signature amyloid plaques, they suggest.

    Moir thinks P. gingivalis is likely one of a variety of pathogens that contribute to the β-amyloid buildup and neuroinflammation. But he’s skeptical that the bacteria or its toxin directly cause Alzheimer’s. That’s partly because other recent studies that have explored the link with periodontal disease have not always found it in people with Alzheimer’s.

    Howard Fillit, a neuroscientist and chief science officer at the nonprofit Alzheimer’s Drug Discovery Foundation in New York City, is more impressed. “They did a lot of different experiments to build the case that gingipains are a drug target in Alzheimer’s disease,” he says. “I think it’s worth pursuing, and I'm glad they're in a clinical trial.”

    If the findings hold up, do they mean that everyone with gum disease—nearly 50% of the U.S. adult population—will develop Alzheimer’s? Not necessarily. But if healthy people want to stay on the safe side and potentially reduce their risk, Noble says, “the main conclusion we still have is: brush and floss.”
    February 12, 2019
    By Megan Schmidt
    A Hormone Produced When We Exercise Might Help Fight Alzheimer’s

    An exercise-induced hormone linked to a range of benefits might add another to its repertoire: protection against Alzheimer’s disease.

    A new paper, published in Nature Medicine, explains that the hormone irisin, released by our bodies when we exert ourselves, seems to offer protection against the memory loss and brain damage associated with Alzheimer’s. In those with the disease, however, irisin levels are depleted. Boosting irisin levels through exercise, then, might be a way to stave off the disease.

    Irisin gets released into our bodies when we use our muscles, and it helps convert fat into heat and energy. This newly-discovered function for the hormone expands its known uses into the mind, and might help explain why lifestyle factors like exercise seem to help slow the progression of Alzheimer’s.

    The results offer new hope for human patients and their families waiting for an Alzheimer’s cure, said Ottavio Arancio, a researcher at Columbia University, who conducted the study in collaboration with an international team of scientists.

    “Our study demonstrates that irisin mediates the beneficial impact of exercise on memory, and offers a novel explanation for how regular exercise may reduce the risk of developing Alzheimer’s disease and why exercise appears to be beneficial for patients at early stages of memory loss,” Arancio said.

    Protective Effect

    The team first looked for the presence of the hormone in brain bank tissue samples. They observed irisin in the human hippocampus and found that levels of the hormone were depleted in brains that were afflicted with Alzheimer’s.

    Next, the team studied how irisin affects the brain using lab mice. They found that mice who swam every day over the course of five weeks did not develop memory problems despite receiving infusions of beta-amyloid — a sticky and clumpy brain protein implicated in Alzheimer’s disease.

    The researchers also treated mice that swam with an irisin-blocking drug. This eliminated the cognitive benefits of swimming. These mice performed no better on memory tests than sedentary mice after being infused with beta-amyloid.

    Together, the findings position irisin as a possible new compound for preventing or treating Alzheimer’s and other forms of dementia in humans, Arancio said.

    However, the study left researchers with some unanswered questions to clear up before a therapy gets off the drawing board. For instance, the underlying mechanisms of irisin’s protective effects aren’t fully understood. It is also unclear whether irisin, which is produced by muscles, is circulated to the brain or if exercise promotes irisin expression in the brain itself.

    But for now, Arancio says irisin holds promise in the fight against Alzheimer’s — whether boosted naturally through exercise or as a new drug therapy in the future.

    “Exercise may be an optimal strategy to ward off dementia. On the other hand, it is important to find effective medications for patients who no longer can exercise adequately,” Arancio said. “Because irisin is a molecule naturally produced by the human organism, it is conceivable that side effects of a potential treatment based on irisin would be reduced.”

    Next, the team will determine whether the beneficial effects of irisin observed in mice will translate to non-human primate brains.

    February 10, 2019
    By Christopher Bergland
    Exercise-Linked Irisin May Protect Against Neurodegeneration

    Exercise-induced irisin rescues synaptic plasticity and may protect memory.

    A new study by an international team of researchers reaffirms the potential neuroprotective power of exercise-induced irisin. Since the hormone irisin was first discovered less than a decade ago, there’s been some debate about whether or not irisin is, in fact, the powerful exercise-induced messenger that the pioneering researchers at Harvard Medical School led by Bruce Spiegelman initially speculated back in 2012.

    The recent study by first author Mychael Lourenco et al., “Exercise-Linked FNDC5/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimer’s Models,” adds to a growing body of evidence that exercise-induced irisin may protect against neurodegeneration and boost memory in both humans and mice. This paper was published January 7 in Nature Medicine.

    An accompanying commentary in this issue of Nature Medicine by Xu Chen and Li Gan—who were not involved in the Lourenco et al. (2019) study—sums up the significance of this research: "An exercise-linked hormone, FNDC5/irisin, mediates the benefit of exercise in Alzheimer’s disease models by enhancing synaptic plasticity and memory."

    The first notable aspect of this three-pronged study is that post-mortem analysis of samples from human brain banks revealed that irisin molecules make their way into the human hippocampus and that hippocampal levels of irisin are significantly reduced in individuals with Alzheimer's disease (AD).

    The second phase of this study used mice to investigate if irisin rescues synaptic plasticity and helps to preserve memory in an animal model. Notably, the researchers found that if they disabled or "knocked out" the effects of irisin in mice, synaptic function and memory both weakened. On the flip side, if they boosted levels of irisin, synaptic plasticity and memory both improved.

    The third part of this study explored the effect of aerobic exercise on irisin levels in the mouse brain. For this arm of the three-part study, the researchers had one cohort of mice swim for 60 minutes/five days a week for five weeks. In comparison to a control group that didn’t swim regularly, the researchers found clear evidence of exercise-linked irisin production.

    Additionally, when the swimming mice were infused with a beta-amyloid (that is implicated in AD) the exercise-linked irisin provided neuroprotection. For example, if the researchers administered a drug that blocked irisin, the brain benefits of swimming became nonexistent. Irisin-blocking substances wiped away any exercise-related improvements on memory tests.

    The multi-faceted findings of this research suggest that exercise-induced irisin may help prevent certain types of dementia in humans. The next phase of ongoing irisin research will be to explore possible pharmaceuticals that can increase levels of irisin in the brain without the need to exercise.

    "In the meantime, I would certainly encourage everyone to exercise, to promote brain function and overall health," co-author Ottavio Arancio of Columbia University said in a statement. "But that's not possible for many people, especially those with age-related conditions like heart disease, arthritis, or dementia. For those individuals, there's a particular need for drugs that can mimic the effects of irisin and protect synapses and prevent cognitive decline."

    The Brief (and Somewhat Controversial) History of Exercise-Induced Irisin

    Seven years ago, Bruce Spiegelman and colleagues at the Dana-Farber Cancer Institute in Boston first reported their discovery of an exercise-induced messenger that seemed to have amazing potential for communicating with various tissues throughout the body and brain.

    Spiegelman and co-authors reported on these findings in a January 2012 study (Boström et al., 2012) published in the journal Nature. In this paper, the authors explain the novelty of their discovery: "Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin."

    Spiegelman coined the name "irisin" for this newly discovered hormone as a shout-out to Iris, who is a messenger of the gods in Greek mythology and Homer's Iliad. Early on, Spiegelman had a hunch that isolating and naming irisin was an important first step for advancing our understanding of how aerobic exercise triggers a chain reaction of benefits throughout the body and brain.

    I first learned about the ability of a relatively unknown exercise-induced molecule called “irisin” to improve cognitive function and protect the brain against neurodegeneration in mice six years ago.

    In an October 2013 post, "Scientists Discover Why Exercise Makes You Smarter," I reported on more cutting-edge research (Wrann et al., 2013) from Spiegelman's lab published in the journal Cell Metabolism.

    Christianne Wrann and co-authors explained the significance of this paper, “Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice."

    Soon after this paper was published, some controversy erupted. Other experts questioned the protocol and validity of Spiegelman’s research methods and his team’s subsequent findings. These naysayers raised some doubts about whether levels of irisin actually increase via aerobic exercise.

    In 2015, Spiegelman and his team addressed these concerns in a paper, "Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry," which confirmed the existence of exercise-linked irisin. The authors (Jedrychowski et al., 2015) said, "In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise." (See "The 'Exercise Hormone' Irisin Is NOT a Myth.")

    Hopefully, the latest study on irisin by Lourenco et al. (2019) will serve as another source of motivation for people of all ages to sit less and exercise more. But again, for those who are unable to exercise for whatever reason, irisin-based pharmaceuticals may offer new hope in the ongoing fight against Alzheimer’s disease and other forms of dementia in the near future. [read more]

    Also covered by: Consumer Affairs and R&D Magazine.
  • BBC World Service - Health Check
    February 6, 2019
    Health Check: Can Aerobic Exercise Improve Thinking Skills in Younger People?

    Editor's Note: In this BBC Sounds podcast, Yaakov Stern, a professor of neuropsychology, explains the findings of his study of the cognitive effects of aerobic exercise. [listen to the podcast, the segment begins at 19:20]

    February 4, 2019
    By Kanika Gupta
    Aerobic Exercise Good For The Brain, Says Study

    Aerobics can improve cognitive processes required for problem-solving and reasoning in adults ages 20 to 67 years, although its effects get better with age, a new study has revealed.

    The new study led by researchers from the Columbia University Vagelos College of Physicians and Surgeons suggests that this may be the first time that a study examined the effects of aerobic exercise on cognitive abilities of people under the age of 55 years.

    Aerobic Exercise Works Wonders On The Brain

    Yaakov Stern, the senior author of the study, assigned 132 adults ages 20 to 67 years that have below average aerobic capacity to an aerobic program of core-strengthening and stretching workouts. The research participants were evaluated for executive function, language, episodic memory, processing speed, and attention at 12 and 24 weeks.

    The findings published in the journal Neurology revealed that there was a notable improvement in the executive functioning of participants of all ages in the aerobic group. In fact, the study found that the executive functions, i.e.reasoning, planning, and problem-solving in participants improved with age after 24 weeks.

    However, the findings further showed that aerobic exercise did not improve cognitive functions such as language, processing speed, episodic memory, or attention in participants of all ages.

    "Executive function usually peaks around age 30," Stern says, "and I think that aerobic exercise is good at rescuing lost function, as opposed to increasing performance in those without a decline."

    Stern further explains that a larger study may be required to identify improvement brought by aerobic exercise in young adults.

    What It Means

    The research indicates that aerobic exercise can significantly improve the cognition of young adults, suggesting that regular cardiovascular workouts can prevent or delay the appearance of an age-related decline in cognitive functions.

    Moreover, the flexibility to choose when and how to exercise can make it easier and more attractive to the general population to adopt aerobics as a way of life.

    Also covered by: Bustle

    January 31, 2019
    Aerobic Exercise Improves Cognition, Even In Young Adults

    In brief

    Aerobic exercise training improves cognition, even for young and middle-aged adults, according to a new study led by researchers at Columbia University Vagelos College of Physicians and Surgeons.

    The study of 132 adults between the ages of 20 and 67 found that aerobic exercise training increases executive function—cognitive processes important for reasoning, planning, and problem-solving—in adults as young as 20, although the effect was stronger with increasing age.

    Why it matters

    The study indicates that aerobic exercise training improves cognition in younger adults, suggesting that exercise can prevent or slow the appearance of at least some age-related cognitive changes.

    The flexibility of the exercise protocol, in which participants choose when and how to exercise, could make the intervention more attractive to the general population and increase its chances for adoption.

    Previous studies focused on elderly

    Most previous studies of exercise and cognition have focused on the elderly, and those that include young adults were small and did not include a randomly assigned control group.

    In the new study, Yaakov Stern, PhD, chief of cognitive neuroscience and a member of the Taub Institute, and Richard Sloan, PhD, chief of behavioral medicine, assigned 132 individuals with below median aerobic capacity to an aerobic exercise training program or to a control program of stretching and core-strengthening exercises.

    All participants worked out at a local YMCA four times a week, and those in the exercise group could choose any form of aerobic exercise as long as they reached target heart rates. Data from heart rate monitors worn by the participants were downloaded to an on-site computer.

    Participants were tested for executive function, processing speed, language, attention, and episodic memory before being assigned to groups and at 12 and 24 weeks.

    Exercise improves the brain’s executive function

    After 24 weeks, there was significant improvement in executive function in the aerobic exercise group for participants of all ages, and the greater the participant’s age, the greater the improvement in executive function.

    “Executive function usually peaks around age 30,” Stern says, “and I think that aerobic exercise is good at rescuing lost function, as opposed to increasing performance in those without a decline.”

    Executive function underlies many day-to-day activities. For example, bill paying requires planning, organizing, and shifting from one related task to another. These activities rely on intact executive function.

    Aerobic exercise did not improve cognitive function in processing speed, language, attention, or episodic memory for participants of any age. Some studies have found that aerobic exercise improves these features in adults above 55, and Stern says that a larger study may be able to detect improvement in younger adults. It’s also possible that exercise has different effects in young vs. older adults.

    Aerobic exercise increases gray matter in brain

    Brain imaging at baseline and 24 weeks revealed that aerobic exercise training is associated with significantly increased cortical thickness in the left caudal middle frontal cortex. The increase in gray matter was not associated with the participant’s age. And increases in gray matter did not correlate directly with a corresponding change in any cognitive domain.

    Still, several aerobic exercise studies in older adults have noted comparable changes in the frontal lobe, suggesting that aerobic exercise has a beneficial effect on a brain area that is associated with executive function. [read more]

    Also covered by: USNews, HealthDay, Reuters, Forbes, New Scientist, CBS Newspath, Healio, and NBC Television Network: TodayOnline.

    More Information

    Yaakov Stern also is professor of neuropsychology in the Departments of Neurology and Psychiatry and a member of the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Irving Medical Center.

    Richard Sloan is the Nathaniel Wharton Professor of Behavioral Medicine in the Department of Psychiatry.

    The study, “Effect of Aerobic Exercise on Cognition in Younger Adults: A Randomized Clinical Trial,” appeared online Jan. 30 in the journal Neurology (link is external).

    Other authors: Anna MacKay-Brandt, PhD (Columbia University Irving Medical Center and Nathan Kline Institute for Psychiatric Research), Seonjoo Lee, PhD (CUIMC and New York State Psychiatric Institute), Paula McKinley, PhD (CUIMC), Kathleen McIntyre, LCSW (CUIMC), Qolamreza Razlighi, PhD (CUIMC), Emil Agarunov (CUIMC), and Matthew Bartels, MD, MPH (CUIMC).

    The study was funded by the NIH (grants R01AG033546 and K01AG051348).

    Yaakov Stern has received a grant from the California Walnut Commission and has been a consultant to Eli Lilly, Axovant, Takeda, and AbbVie. Matthew Bartels has grant support from AposTherapy, Inc., LIH Medical, and Everest Foundation.

    By Gretchen Reynolds
    January 17, 2019
    How Exercise May Help Keep Our Memory Sharp

    Irisin, a hormone that is released during exercise, may improve brain health and lessen the damage that occurs during Alzheimer’s disease.

    A hormone that is released during exercise may improve brain health and lessen the damage and memory loss that occur during dementia, a new study finds. The study, which was published this month in Nature Medicine, involved mice, but its findings could help to explain how, at a molecular level, exercise protects our brains and possibly preserves memory and thinking skills, even in people whose pasts are fading.

    Considerable scientific evidence already demonstrates that exercise remodels brains and affects thinking. Researchers have shown in rats and mice that running ramps up the creation of new brain cells in the hippocampus, a portion of the brain devoted to memory formation and storage. Exercise also can improve the health and function of the synapses between neurons there, allowing brain cells to better communicate.

    In people, epidemiological research indicates that being physically active reduces the risk for Alzheimer's disease and other dementias and may also slow disease progression.

    But many questions remain about just how exercise alters the inner workings of the brain and whether the effects are a result of changes elsewhere in the body that also happen to be good for the brain or whether the changes actually occur within the brain itself.

    Those issues attracted the attention of an international consortium of scientists — some of them neuroscientists, others cell biologists — all of whom were focused on preventing, treating and understanding Alzheimer's disease.

    Those concerns had brought a hormone called irisin into their sphere of interest. Irisin, first identified in 2012 and named for Iris, the gods' messenger in Greek mythology, is produced by muscles during exercise. The hormone jump-starts multiple biochemical reactions throughout the body, most of them related to energy metabolism.

    Because Alzheimer's disease is believed to involve, in part, changes in how brain cells use energy, the scientists reasoned that exercise might be helping to protect brains by increasing levels of irisin there.

    But if so, they realized, irisin would have to exist in human brains. To see if it did, they gathered tissues from brain banks and, using sophisticated testing, found irisin there. Gene expression patterns in those tissues also suggested that much of this irisin had been created in the brain itself. Levels of the hormone were especially high in the brains of people who were free of dementia when they died, but were barely detectable in the brains of people who had died with Alzheimer's.

    Those tests, however, though interesting, could not tell scientists what role irisin might be playing in brains. So the researchers now turned to mice, some healthy and others bred to develop a rodent form of Alzheimer's.

    They infused the brains of the animals bred to have dementia with a concentrated dose of irisin. Those mice soon began to perform better on memory tests and show signs of improved synaptic health.

    At the same time, they soaked the brains of the healthy animals with a substance that inhibits production of irisin and then pumped in a form of beta amyloid, a protein that clumps together to form plaques in the brains of those with Alzheimer’s. In effect, they gave the mice dementia. And, without any irisin in their brains, the once-healthy mice soon showed signs of worsening memory and poor function in the synapses between neurons in their hippocampus.

    The scientists also looked inside individual neurons from healthy mice and found that, when they added irisin to the cells, gene expression changed in ways that would be expected to lessen damage from beta amyloid.

    Finally and perhaps most important, the scientists had healthy mice work out, swimming for an hour almost every day for five weeks. Beforehand, some of the animals also were treated with the substance that blocks irisin production.

    In the untreated animals, irisin levels in the brain blossomed during the exercise training and later, after the animals' brains were exposed to beta amyloid, they seemed to fight off its effects, performing significantly better on memory tests than sedentary control mice that likewise had been exposed.

    But the animals that had been unable to create irisin did not benefit much from exercise. After exposure to beta amyloid, they performed about as poorly on memory tests as sedentary animals with beta amyloid in their brains.

    Taken as a whole, these experiments suggest that exercise may protect against dementia in part by triggering an increase in the amount of irisin in the brain, says Ottavio Arancio, a professor of pathology and cell biology at Columbia University, who conducted the research along with two dozen colleagues from the Federal University of Rio de Janeiro in Brazil, Queen's University in Canada and other institutions.

    But the experiments, although elaborate and multipronged, used mice, and so cannot tell us if exercise and irisin will work similarly in people, or how much and what types of exercise might be best for brain health. The results also do not show whether exercise and irisin can prevent Alzheimer's, but only that they seem to allay some of the effects of the disease in mice once it begins.

    The scientists involved in the study hope soon to test a pharmaceutical form of irisin as a treatment for dementia in animals and eventually people, especially those who have lost the ability to exercise, Dr. Arancio says.

    But for now, he says, the overarching lesson of the study would seem to be that "if you can, go for a walk."

  • bottom bar