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Taub Institute news and events


2018 - 2017 | 2016 - 2011

    August 1, 2018
    For Patients with Depression and Mild Cognitive Impairment, Popular Alzheimer’s Medication Is Not Effective

    Results from a clinical trial conducted by Columbia University Irving Medical Center and Duke University Health System suggest that donepezil—an Alzheimer’s drug—may not improve cognitive performance in people at risk for Alzheimer’s disease who also had depression.

    The study’s findings were published in the July 2018 issue of the American Journal of Geriatric Psychiatry, the medical journal of the American Association for Geriatric Psychiatry.

    More than 5 million Americans and 40 million people worldwide have mild cognitive impairment. Studies have shown that about 30 percent of people with mild cognitive impairment also have clinical depression.

    "Both late-life depression and mild memory loss are established risk factors for dementia, and when they co-occur, the risk for future dementia is even higher. That is why it is critical to find effective therapies for this population," said study author Devangere Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry at Columbia University Vagelos College of Physicians and Surgeons.

    Co-author Murali Doraiswamy, MD, professor of psychiatry and medicine at Duke University Health System added, "There are no FDA-approved therapies for preventing dementia in at-risk people with both mild cognitive impairment and depression. Cholinesterase inhibitors used to treat Alzheiemer’s, such as donepezil, and a variety of supplements are often used in clinical practice to treat such patients, but their efficacy in this population isn’t proven."

    The study enrolled 79 people who were experiencing both mild cognitive impairment and major depression. Participants were first given standard antidepressant treatment for 16 weeks. During this time, 64 percent of the group had an improvement in their depression symptoms. Subjects were then randomly assigned either to additional daily treatment by donepezil or placebo for another 62 weeks. Compared with placebo, donezepil did not produce a significant improvement in cognitive performance, daily functioning, or slowing of the progression to dementia. In addition, patients who were treated with donepezil experienced more adverse effects than those on placebo.

    Dr. Devanand noted that implications of these results run counter to the common practice of treating people who have both depression and cognitive impairment with cholinesterase inhibitors. Dr. Doraiswamy emphasized that their findings highlight the need to prioritize discovery of novel Alzheimer’s treatments for people who also have depression.

    The study is titled, "Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial."

    The other authors of this paper are Gregory H. Pelton, MD, Kristina D'Antonio, MSW, Adam Ciarleglio, PhD, Jennifer Scodes, MS, Howard Andrews, PhD, Julia Lunsford, MD, John L. Beyer, MD, Jeffrey R. Petrella, MD, Joel Sneed, PhD, and Michaela Ciovacco, BA.

    This study was supported by the National Institute on Aging NCT01658228.

    Dr. Devanand has served as an advisor to pharmaceutical companies and Dr. Doraiswamy has also served as an advisor to pharmaceutical companies and advocacy groups for other projects. [read more CUIMC news]

    June 15, 2018
    Alzheimer Drugs Keep Failing, Can Big Data Help?

    This week another pharmaceutical company announced it had given up on developing an Alzheimer’s drug, and the news was not a surprise. It follows announcements just this past May and February of other abandoned drug candidates to slow the disease, and dozens more over the past 20 years.

    Many of the failed drug candidates have something in common: They target amyloid, which accumulates in the brain of people who go on to develop Alzheimer’s. Have drug developers been focusing on the wrong target?

    "Amyloid is most certainly implicated in Alzheimer’s, but the disease is far more complex than we’ve appreciated," says Philip L. De Jager, MD, PhD, a neurologist at Columbia University’s Vagelos College of Physicians and Surgeons.

    "It’s clear that we need to find completely new strategies to prevent or at least slow the progression of the disease, but we’re just now developing the tools to understand the disease’s complexity."

    "Big data" approaches like network analysis have been used to unravel the complex molecular pathways that govern cancer, but their use in Alzheimer’s research has lagged behind.

    "One advantage with cancer is that tissue samples are usually accessible," De Jager says. "In neurological diseases, we haven’t had enough brain tissue from people who were tracked carefully as they developed dementia to do these sorts of analyses."

    De Jager’s recent worksuggests that Alzheimer’s is now ready for big data studies.

    Over the past 20 years, De Jager’s colleague David Bennett at Rush University Medical Center has been building up a repository suitable for such data mining. The repository now includes years of data from more than 3,000 people, including how cognition changed over time in each individual and samples of brain tissue from the more than 1,200 participants who are now deceased.

    Recently, De Jager, Bennett, and colleagues at the University of British Columbia and Brigham and Women’s Hospital began to tap into the resource. Their effort is part of the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD), a collaboration among the NIH, pharmaceutical companies, and nonprofit organizations to transform the way new Alzheimer’s treatments are developed. De Jager and Bennett were one of the first three groups awarded funding from AMP to use big data techniques to identify new drug targets.

    De Jager’s team started by sequencing more than 12,000 genes in each individual brain to determine their level of expression. Rather than focus on individual genes, the researchers used a type of analysis that creates a network of genes that work together to hasten cognitive decline or accumulation of brain pathologies.

    With this network diagram in hand, they then looked for the small number of genes in the network that appear to drive the changes seen in the study’s participants. Such "driver genes" are potentially excellent targets for new Alzheimer drugs, because as the network’s nodal points, turning them on or off may have the greatest therapeutic effect. One can think of them as the switches in a complicated circuit that open or close a whole series of downstream events.

    "Capturing all of these data allowed us to look for patterns related to the disease without making any assumptions about what was important," De Jager says.

    The researchers recently reported results from this analysis in Nature Neuroscience.They describe 11 groups of genes or modules that appear to directly affect cognitive decline, amyloid, and other Alzheimer’s-related traits.

    The team focused attention on one module that seemed most related to cognitive decline and among its 390 genes identified two bona fide driver genes that, when active, increase the production of amyloid. One gene had never been linked to Alzheimer’s. By silencing either one, amyloid levels in the cells were significantly reduced.

    These genes may be good therapeutic targets, says De Jager, though more work is needed to confirm their role in disease and to understand how they function.

    Many other therapeutic targets within the data await discovery (the researchers only validated the role of one of the 11 modules involved in the disease). In an effort to accelerate Alzheimer’s research worldwide, all of the data and the resulting network models have been made publicly available to encourage independent investigations by other researchers.

    "What’s really significant about our study is that it demonstrates how big data and advanced analytic techniques can be used to identify genes that are important in Alzheimer’s disease and are excellent new targets for drug development," De Jager says. [read more CUIMC news]
    June 15, 2018
    By Denise C. Park
    What Do We Know about ‘Heading’ and Concussion Risk?

    In soccer, athletes frequently use their heads to connect with the ball. But researchers have raised concerns about the potential risk of concussion from heading the soccer ball. As the World Cup enthralls soccer fans from around the globe, how concerned should we be about heading?

    The CUIMC Newsroom interviewed James Noble, MD, a neurologist who studies concussion risk in athletes, about what the research says—and doesn’t say—about the dangers of heading in soccer.

    Q: What is it about heading a soccer ball that could be dangerous for the brain?

    Researchers have been asking if heading itself—the impact from the ball making contact with the head—is dangerous for the brain or if the real danger comes from the accidental collision of two athletes who are trying to head the same ball. It’s probably both. Other factors, such as age, size, gender, and aggressiveness of play, could influence concussion risk. Researchers need to determine if there’s something specific to younger athletes or professional athletes that may incur different levels of risk.

    Q: How do researchers study this issue?

    Some approaches assess an athlete’s exposure to head impacts. Studies have used accelerometers that are embedded in helmets, headbands, and mouth guards. These tools measure movement, which is a proxy for the force of an impact, though they don’t measure how the brain responds to that impact.

    A number of tests can be performed on the sidelines to get a better idea of the effect of head impacts. Doctors can do a neurological exam to look for signs of concussion. MRI and other specialized scans can look for physical evidence of brain trauma. EEG can identify brain wave patterns associated with concussion.

    But athletes often don’t speak up when they’ve been injured. So the real challenge lies in identifying the athlete who needs to be evaluated to determine the impact on the brain. I’m currently developing a helmet that’s embedded with miniaturized EEG technology to send a signal to the sidelines, in real time, when an athlete has a concussion. The technology could be adapted for non-helmeted sports, including soccer.

    Q: Should we only be concerned about concussions? Is heading risky even without concussion?

    We think that the subconcussive injuries—brain injuries without obvious signs or symptoms—that accumulate over an athlete’s career may be more important in terms of brain injury. Concussions may just be the tip of the iceberg.

    Q: Your research suggests that female athletes are at increased risk for concussion compared with males. Is this also true for female soccer players?

    At Columbia, we looked at the risk of brain injury in college athletes, men and women, in all contact sports—not just soccer. There are two collegiate consortia now studying sport-specific concussions in female athletes. So far, research suggests that female athletes have similar or higher risk for concussion compared with male athletes, especially at the college level.

    Q: Recent lawsuits against FIFA, US Soccer, and the American Youth Soccer Organization call for age limits on heading the ball. What are some of the possible age-related risks related to concussion in soccer?

    Age-related risks could be related to brain maturity and response to injury, whether or not an athlete reports a suspected concussion, body development, pre-existing medical problems, and even genetic risk factors. There are so many connected factors here that still need to be sorted out.

    Q: Do we know enough about the effects of heading to ban it?

    I don’t think so, since a lot remains uncertain, and a call to ban something in organized sports requires a lot of clear and convincing evidence to make the case. Certainly it’s important to avoid head injury in any sport, and we think this is going to turn out to be especially critical for youth athletes. The movement to avoid heading, including heading drills, until the teen years is a good first move until the risks are clear. But while we are just starting to understand the short- and long-term risks of head impacts and subconcussive injuries in other sports, we don’t know the long-term outcomes of heading specifically, or if there’s a threshold age and number of headers—per day, week, season, or career—that we need to be concerned about.

    If league organizers, parents, coaches, players, and researchers work together, we could answer these questions. As a field, we’re working towards developing sport-specific and age-specific policies that better protect athletes.

    Being athletic has a range of health and social benefits that can last a lifetime. The goal isn’t to steer athletes away from participating in sports like soccer; instead, we should use evidence of the near- and long-term risks to help athletes play safely. This is particularly true for youth athletes, who can’t make decisions for themselves about how they should play or how the game is played. Helmets aren’t the answer, since there’s no completely concussion-proof helmet or headgear. But we can prepare athletes for heading—or avoiding heading—with education and physical training.
    [read more]
    Dr. Noble is an assistant professor of neurology (in the Taub Institute and the Sergievsky Center) at Columbia University Vagelos College of Physicians and Surgeons. He also participates in research with the Big 10-Ivy League Traumatic Brain Injury Research Collaboration, is the chief medical officer and co-founder of NoMo Diagnostics (nomodx.com (link is external)), and is an independent neurological consultant for professional teams, including the NFL.
    June 15, 2018
    By Denise C. Park
    Five Myths About Alzheimer’s Disease
    It turns out, however, that a life of privilege (financial security, higher social class and high levels of education) appears to confer some limited protection from Alzheimer’s. For example, Yaakov Stern of Columbia University studied 593 older adults who lived in Manhattan and found that over time, those who were less educated and held lower-status jobs were diagnosed with the disease at younger ages compared with those who were more privileged. [read more]
    April 24, 2018
    By Alison Abbott
    Is 'Friendly Fire' in the Brain Provoking Alzheimer’s Disease?
    Scientists want to combat dementia and neurodegeneration by keeping the brain’s immune system from going rogue. [read more]
    Produced by Sarah Wyman
    Life Outside the Lines
    Creating art with dementia

    In early 2017, Sarah's grandfather passed away from complications of vascular dementia. Her family never truly dealt with his diagnosis, and the end of his life felt totally disconnected from how he lived. So Sarah set out in search of a better way to live with dementia.
    This is what she found. [listen to the podcast]
    Columbia Named Research Center of Excellence by Lewy Body Dementia Association
    The Lewy Body Dementia Association (LBDA) has announced the launch of the LBDA Research Centers of Excellence (RCOE), a comprehensive network of 24 academic medical centers—including Columbia—that will work together with a common goal to improve the understanding of the disease in the scientific, medical and general public communities. The LBDA RCOE program aims to establish a clinical trials-ready network of leading institutions that share the common vision of providing the highest level of clinical care over the course of LBD treatment. In addition, the RCOE network seeks to increase access to support for caregivers and people living with LBD, increase the knowledge of LBD among the medical community, and construct administrative infrastructure and generate the resources necessary to further advance LBD research and care.

    The centers were chosen for their clinical expertise in LBD, experience running clinical trials in related conditions (combined, the 33 PIs have run 380 clinical trials in the past 5 years), their facility's capacity and willingness to participate, and their geographic locations. The 24 RCOEs are spread across 17 states and the District of Columbia and are located in 23 American metropolitan areas. Each RCOE is led by recognized primary investigators (PIs) and co-investigators to conduct trials and provide expert care. Columbia Neurology faculty members Drs. Lawrence Honig and Karen Marder will serve as the co-directors/co-principal investigators of Columbia’s LBDA RCOE site.

    More information on the LBDA RCOE program can be found on LBDA's website at https://www.lbda.org/rcoe.
    January 24, 2018
    Alzheimer's Drug Targeting Soluble Amyloid Falls Short in a Large Clinical Trial
    A paper published today in the New England Journal of Medicine reports that solanezumab, a monoclonal antibody-based treatment for Alzheimer's disease developed by Eli Lilly that targets amyloid plaques, did not significantly slow cognitive decline.

    Researchers have proposed that Alzheimer's disease is caused by the buildup of a sticky protein called beta-amyloid. According to this "amyloid hypothesis," the protein forms plaques in the brain that damage and eventually destroy brain cells. Solanezumab was designed to reduce the level of soluble amyloid molecules before they aggregate.

    A total of 2,129 patients with mild dementia due to Alzheimer’s disease participated in the double-blind, placebo-controlled, phase 3 multicenter trial. This study was the first major Alzheimer’s clinical trial to require molecular evidence of amyloid deposition in the brain for enrollment. While the treatment did have some favorable effects, in the main measure of outcome—measured with a cognitive test called the Alzheimer’s Disease Assessment Scale-cognitive subscale—the researchers did not observe any statistically significant benefit compared with placebo.

    The authors suggest that while it is not certain that this particular strategy or drug could be effective, it is possible that either not enough drug was administered or that the drug needs to be administered earlier in the disease course.

    In other studies ongoing at Columbia University Irving Medical Center and other centers, solanezumab is being evaluated in presymptomatic patients at risk of Alzheimer’s disease. Other Alzheimer's drugs are also in development and being tested at higher doses.

    "Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study," says lead author Lawrence Honig, MD, PhD, professor of neurology at CUIMC. "There is hope that one of the newer ongoing studies may result in an effective treatment for slowing the course of Alzheimer's disease." [read more]

    Also covered by: STATnews and TIME
    November 17, 2017
    Drop-Off in Dementia in Northern Manhattan Echoes National Trend
    Dementia, including Alzheimer’s disease, is on the decline among northern Manhattan seniors, following national and global trends. The findings, by researchers at Columbia University Medical Center, were reported last month in the Journal of Alzheimer's Disease. The study found a 41 percent drop in dementia risk for seniors from Washington Heights and Inwood who joined a Columbia University-sponsored aging study in 1999 compared with a similar group that enrolled in 1992. Both groups included a multi-ethnic mix of non-Hispanic whites, African-Americans, and Hispanics. "It's important to look at a variety of populations so that we can determine if changes in dementia rates are occurring on a local, national, or global trend and to identify both common and population-specific factors that may be contributing to the overall picture," says James Noble, MD, assistant professor of neurology at Columbia University Medical Center (CUMC) and co-lead author of the study. "This is especially true in the U.S., where there are often racial, ethnic, and geographic disparities in health that are attributable to a variety of factors, from access to care to education." [read more]
    New York, NY (November 10, 2017) – Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) may have discovered a way to use a patient's sense of smell to treat Alzheimer's disease before it ever develops. Having an impaired sense of smell is recognized as one of the early signs of cognitive decline, before the clinical onset of Alzheimer's disease. The researchers at CUMC and NYSPI have found a way to use that effect to determine if patients with mild cognitive impairment may respond to cholinesterase inhibitor drugs to treat Alzheimer's disease.

    The findings were published online this week in the Journal of Alzheimer's Disease.

    Cholinesterase inhibitors, such as donepezil, enhance cholinergic function by increasing the transmission of the neurotransmitter acetylcholine in the brain. Cholinergic function is impaired in individuals with Alzheimer's disease. Cholinesterase inhibitors, which block an enzyme that breaks down acetylcholine, have shown some effectiveness in improving the cognitive symptoms of Alzheimer's disease. However, they have not been proven effective as a treatment for individuals with mild cognitive impairment (MCI), a condition that markedly increases the risk of Alzheimer's disease.

    "We know that cholinesterase inhibitors can make a difference for Alzheimer’s patients, so we wanted to find out if we could identify patients at risk for Alzheimer's who might also benefit from this treatment," said D.P. Devanand, MBBS, MD, professor of psychiatry, scientist in the Gertrude H. Sergievsky Center at CUMC, and co-director of the Memory Disorders Clinic and the Late Life Depression Clinic at NYSPI. "Since odor identification tests have been shown to predict progression to Alzheimer's, we hypothesized that these tests would also allow us to discover which patients with MCI would be more likely to improve with donepezil treatment." [read more] [CUIMC NEWSROOM]

    Also covered by PsychCentral
    October 3, 2017
    Drugs Can't Stop Alzheimer's. A New Model of the Disease Explains Why.
    A new model of Alzheimer’s disease – proposed by scientists at Columbia University Medical Center and Weill Cornell Medicine – may explain why clinical trials of potential Alzheimer's drugs have a high failure rate. CUIMC NEWSROOM spoke with co-author Scott Small, MD, the Boris and Rose Katz Professor of Neurology, about the theory, published in a new article in Trends in Neuroscience. [read more]
  • SELF
    By Emily Rekstis
    August 28, 2017
    I Have a 50/50 Chance of Developing Huntington's Disease
    Featuring Jill Goldman
    It feels so certainly uncertain. I don't remember the exact moment I found out my dad had Huntington's disease, or how I found out it was genetic. What I do remember is showing off, in high school biology, that I knew the Huntington's gene was dominant in males. My reasoning was that my dad, his dad, and his granddad all had Huntington's. I knew my two sisters and I still had a chance at getting it, but it wasn’t as likely. This, of course, is not true...

    People at risk don’t have to live in this in-between world.

    The uncertainty can be put to rest by a not-so-simple genetic test. Jill Goldman, genetic counselor at the Taub Institute at Columbia University Medical Center, tells SELF that there is an international protocol which includes a DNA component that can reveal whether an individual will develop the disease. First, the person at risk will call an HD or movement disorder clinic to get information such as what the protocol entails, what the risks are, and what it costs. [read more]
    By David Noonan
    June 12, 2017
    Smell Test May Sniff Out Oncoming Parkinson's and Alzheimer's
    Featuring Dr. Davangere Devanand
    Sight and hearing get all the glory, but the often overlooked and underappreciated sense of smell—or problems with it—is a subject of rapidly growing interest among scientists and clinicians who battle Alzheimer's and Parkinson's diseases. Impaired smell is one of the earliest and most common symptoms of both, and researchers hope a better understanding will improve diagnosis and help unlock some of the secrets of these incurable conditions...

    "It's important, not just because it's novel and interesting and simple but because the evidence is strong," says Davangere Devanand, a professor of psychiatry and neurology at Columbia University. His most recent paper on the subject, a review, was published in The American Journal of Geriatric Psychiatry in December.[read more]
    Neuro-immunology Specialist

    Philip De Jager, PhD, MD, MMSc
    The Department of Neurology is very pleased to announce that Philip De Jager, PhD, MD, MMSc has joined our faculty as Professor of Neurology (in the Taub Institute for Research on Alzheimer's disease and the Aging Brain (link is external) and the Columbia Precision Medicine Initiative). After graduating from Yale University with a degree in Molecular Biophysics & Biochemistry (as well as Medieval French literature), Dr. De Jager received a PhD in Neurogenetics from Rockefeller University and an MD from Cornell University Medical College before completing his MMSc in Clinical Investigation at Harvard Medical School (HMS) and MIT. He served as a neurology resident in the Partners Neurology Residency Program at the Massachusetts General Hospital and Brigham and Women’s Hospital. He then joined the faculty at HMS, rising to the rank of associate professor before joining CUMC. The goal of Dr. De Jager's work as a clinician-scientist is to apply modern methods of neuro-immunology, statistical genetics, and systems biology to the understanding of common neurodegenerative diseases. In Neurology, Dr. De Jager will serve as chief of a new Division of Neuro-immunology, which will include a new Center for Translational & Systems Neuro-immunology that he will direct, as well as the Multiple Sclerosis Clinical Care and Research Center, directed by Dr. Claire Riley. The focus of this new division will be to characterize and target the neuro-immunologic component of neurodegenerative disease. Please join us in welcoming Dr. De Jager to Neurology and CUMC!
  • CNBC
    March 15, 2017
    Brain Aging Linked to Common Genetic Variant
    A group of researchers has discovered a genetic variant that appears to have a significant impact on how quickly the brain ages in older people, and that may influence a person's risk of developing neurodegenerative diseases. The research was reported Wednesday in the journal Cell Systems. "If you look at a group of seniors, some will look older than their peers and some will look younger," said the study's co-author Asa Abeliovich in a news release. "The same differences in aging can be seen in the frontal cortex, the brain region responsible for higher mental processes." [read more]

    Also covered by Bioscience Technology, International Business Times, and Daily Mail.
    February 28, 2017
    Concussions More Likely in Female Athletes
    Female athletes appear to be more likely than men to suffer concussions during their careers on the field, a new study suggests.

    The findings add to the existing evidence that female athletes may be more susceptible to concussions, even as attention has tended to focus on the risk to male football players.

    "The more we look at concussion, the more we realize that women are at high risk," said study co-author Dr. James Noble. He's an assistant professor of neurology at Columbia University Medical Center in New York City... [read more]
    February 7, 2017
    Science & U!
    Editor's Note: In Segment 3, neurologist Dr. Richard Mayeux illuminates early onset dementia. [watch video]
    January 19, 2017
    In Alzheimer's, Excess Tau Protein Damages Brain's GPS
    Columbia University Medical Center (CUMC) researchers have discovered that the spatial disorientation that leads to wandering in many Alzheimer's disease patients is caused by the accumulation of tau protein in navigational nerve cells in the brain. The findings, in mice, could lead to early diagnostic tests for Alzheimer's and highlight novel targets for treating this common and troubling symptom.

    The study was published online today in the journal Neuron.

    An estimated three out of five people with Alzheimer's disease wander and get lost, usually beginning in the early stages of the disease, leaving them vulnerable to injury. Researchers suspect that these problems originate in an area of the brain known as the entorhinal cortex (EC). The EC plays a key role in memory and navigation and is among the first brain structures affected by the buildup of neurofibrillary tangles that are largely composed of tau, a hallmark of Alzheimer's disease. "Until now, no one has been able to show how tau pathology might lead to navigational difficulties," said co-study leader Karen E. Duff, PhD, professor of pathology & cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at Columbia... [read more]

    Also covered by: Lab Chat (STAT), Genetic Engineering & Biotechnology News, Cosmos Magazine, Medical News, ScienceDaily, Medical News Today, Daily Mail, Mirror, PsyPost, Alzheimer's Reading Room, and Medical Xpress.
    By Allison Huseman
    January 5, 2017
    Familial Test Helps Detect Genes that Cause Complex Diseases
    Featuring Dr. Richard Mayeux
    A team of researchers at Baylor College of Medicine has developed a family-based association test that improves the detection in families of rare disease-causing variants of genes involved in complex conditions such as Alzheimer's. The method is called the rare-variant generalized disequilibrium test (RV-GDT), and it incorporates rare, as opposed to common, genetic variants into the analysis... [read more]
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