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UCI Generates Preliminary Evidence of a Gene Mutation That May Reduce Risk of Alzheimer’s Disease

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Image Courtesy: AARP Through new developments in Alzheimer’s research, UCI scientists have uncovered evidence of P522R, a particular gene mutation that may aid in minimizing the risk of developing Alzheimer’s disease. Alzheimer’s disease is a progressive disorder that slowly deteriorates memory and thinking skills in the brain, eventually leading to a loss in the ability to complete simple tasks such as  facilitating a conversation or responding to a stimulus in the environment. With the discovery of the disease in 1906 by Dr. Alois Alzheimer, its causes today are focused on two suspects: plaques and tangles in proteins. Beta-amyloid, fragments of…
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For people with Down syndrome, a longer life, but under a cloud

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The Washington Post - April 7, 2022 The FDA approval of Aduhelm ignited a raging debate, with many doctors saying they would not prescribe the drug and several insurers declining to pay for it. Yet even with the uncertainty surrounding the drug, said Elizabeth Head, , at the University of California, Irvine, it is understandable why some families, especially those in which a loved one with Down syndrome faces an all but certain fate, “might believe doing something is better than doing nothing.”
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Study links early life adversity, microglia dysfunction, to aberrant adult stress responses, mental illness

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"Much of neuroscience and study of brain diseases has focused on the brain's neurons. This study highlights that in addition to neurons, other brain cells, and especially immune cells, play crucial roles in brain health and disease," said Tallie Z. Baram, distinguished professor in the Departments of Anatomy & Neurobiology, Pediatrics, Neurology, and Physiology & Biophysics at the UCI School of Medicine. "Neuroimmune interactions are a novel, important avenue to understanding and treating several brain disorders and mental illness and have been linked by other UCI researchers to Alzheimer's disease."
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‘First person’ interview with Gianna Fote in the Journal of Cell Science

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First author Gianna Fote was recently interviewed by the Journal of Cell Science for a newly-published paper. She provided commentary on her team's new findings for UCI MIND: "In our recently published work we studied intracellular trafficking of Apolipoprotein E (APOE), a lipid-carrying protein. The APOE4 isoform of this protein is the biggest genetic risk factor for late-onset Alzheimer’s disease. We found that that APOE can be degraded by a process called autophagy, a process in which cellular waste is transported to an acidic organelle called the lysosome. The APOE4 isoform accumulates in the lysosome and causes increased induction of…
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New Preventive Vaccine for Alzheimer’s Disease Gets Grant

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David Sultzer, MD, Professor, Psychiatry & Human Behavior, School of Medicine eturbonews: The Institute for Molecular Medicine (IMM), a non-profit organization dedicated to basic and translational molecular research to develop safe, effective vaccines against #Alzheimers disease and other #neurodegenerative disorders, today announced that it was awarded a $12 million grant from the National Institute on Aging (NIA) division of the U.S. National Institutes of Health (NIH)​ to support clinical trials of its beta-#amyloid (Aβ) vaccines based on DNA (AV-1959D) and recombinant protein (AV-1959R) for the prevention of Alzheimer’s disease (AD). In collaboration with the @ucirvine (Principal Investigator, David Sultzer, M.D.)…
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Frequent and Feared. But Can Dementia Be Avoided?

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Managed Healthcare Executive - March 17, 2022 According to the CDC, about 5 million Americans have Alzheimer’s disease …. “These numbers are projected to increase because elderly individuals are the fastest-growing segment in the United States,” says Claudia H. Kawas, M.D., a professor in the Department of Neurology at the University of California, Irvine, School of Medicine. … The things known about dementia risk that are potentially modifiable are all related to general health and maintenance of health, says Kawas, noting the association between control of high blood pressure and cholesterol levels and a lower risk of dementia.
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Inside the brain: The role of neuropathology in Alzheimer’s disease research

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90+ Study: Learning from the oldest-old Researchers can learn a lot about how Alzheimer’s develops by studying people at increased risk. People older than age 90, or the oldest-old, are the fastest growing segment of the population in the United States and most of the world and have the highest rates of dementia. Remarkably, the oldest-old also have the highest rate of cognitive resilience and somehow avoid developing dementia despite having brain pathologies. This populations’ high rates of dementia, yet also resilience, make it an optimal group to study to understand the underlying causes of dementia. The 90+ Study, launched in…
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Determining if Dementia Is Uniquely Human

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Discover Magazine: Aging dogs can develop canine cognitive dysfunction (CCD), sometimes known as “doggie dementia.” The brains of dogs with CCD show only amyloid beta plaques, not tau tangles, but their symptoms are similar to the symptoms of dementia in humans, explains Elizabeth Head, director of the graduate program in experimental pathology at the University of California, Irvine. “They’ll forget how to signal that they need to go out,” Head says. “In the more severe stages of the disease, they can become incontinent and may not recognize people.” She points out that because dogs live closely with humans, any behavioral changes…
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Behind a Good Mutation: UCI MIND researchers use stem cells to study a ‘genetic mutation’ that protects against Alzheimer’s Disease

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Contributed by Hayk Davtyan, Ph.D. and Christel Claes, Ph.D. While the word “mutation” may conjure up alarming notions, a mutation in brain immune cells serves a positive role in protecting people against Alzheimer’s disease. Now UCI MIND biologists have discovered the mechanisms behind this crucial process. Their paper appears in the journal Alzheimer’s and Dementia. The investigation centered on a variant of the PLCG2 gene, which makes the instructions for producing an enzyme important to brain immune cells called microglia. “Recently the mutation, which is known as P522R, was shown to lower the risk of developing late-onset Alzheimer’s,” said Hayk…
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UCI receives renewal of designation as Huntington’s Disease Society of America Center of Excellence

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Renewal recognizes UCI's dedication to patient care and active engagement in research to develop new therapeutic approaches February 15, 2022 “Renewal of certification as a Huntington’s Disease Society of America Center of Excellence is very exciting, as this will help us expand our patient care and research. HD was one of the first diseases for which a genetic cause was determined and serves as a paradigm for research into other such diseases,” says Leslie Thompson, Ph.D., Donald Bren and Chancellor’s professor in the departments of psychiatry and human behavior and biological chemistry at the UCI School of Medicine. UCI has…
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University Of California, Irvine Launches Institute For Precision Health

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UCI MIND #InTheNews: Forbes: "According to UCI, the new center will involve collaborations across seven areas: SMART (statistics, machine learning-artificial intelligence) designs software to integrate and analyze health records, molecular data, and observation. This unit will be led by Daniel Gillen, professor and chair of statistics, and Zhaoxia Yu, associate professor of statistics... Precision omics generates, analyzes, and administers genomic, proteomic, and chemical data. It’s led by Suzanne Sandmeyer, professor of biological chemistry, and Leslie Thompson, the Donald Bren and Chancellor's Professor of psychiatry & human behavior at UCI... The institute will take special aim at diseases that heretofore have lacked effective treatments. “For many…
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More healthy behaviors = lower risk of Alzheimer’s, research shows

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UCI MIND #InTheNews   @Seniors Matter - Feb. 9, 2022 “People who engaged in more healthy behaviors had a lower risk than people with fewer because all of these things matter, and when it comes to brain-healthy behaviors, more is more!” said Joshua Grill, PhD, a professor of psychiatry and human behavior at the University of California, Irvine. “So, we should all try to adopt as many brain-healthy behaviors as we can.”
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What Memories Are Made Of

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Our memories are imperfect treasures – dear to our hearts, but not necessarily accurate snapshots of reality. CNN's Chief Medical Correspondent Dr. Sanjay Gupta talks to neurobiologist Michael Yassa about how memories are stored in the brain, why we forget, and what we’ve gotten wrong about how it’s supposed to work. To help understand the mechanisms of memory, we meet a woman who remembers absolutely everything... and a man who can’t even recall what he ate for breakfast. Plus, actionable tips for how we can keep our memories sharp at any age.
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First person interview – Gianna Fote

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Originally posted on The Company of Biologists "First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers." UCI MIND trainee Gianna Fote was recently selected for an interview to discuss her latest publication. Read the full interview here, and learn about her publication here.
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Understanding Why Certain Memories Flood Back (And Others Don’t)

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As a child in the early 1980s, I was enamored with My Little Pony, the colorful plastic horse figurines with long manes. I also had the brand’s Show Stable, which was parked in our TV room and filled with my beloved ponies. But as I progressed through grade school, I eventually packed up my stable and forgot about the toys I once loved.   By late 2003, I hadn’t thought about my ponies for over 15 years. Then, VH1 ran a 1980s nostalgia show in which celebrities reminisced about bygone pop culture. An actress held up a My Little Pony figurine…
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Boosting the Brain’s Brakes to Beat Memory Loss

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Overactivity in the hippocampus, likely tied to lack of inhibition, underlies some age-related cognitive decline. Targeting those circuits shows early promise in slowing memory loss. By Emily Singer December 9, 2021 As we get older, our memory begins to fail in predictable ways. We’re more likely to confuse similar memories, for example, forgetting whether it was little Tim or Samantha who threw the turkey leg across the room at Thanksgiving, and whether that happened the same year the dog snatched the sweet potato pie. In experiments in the lab, old people can easily remember very different objects but have a…
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Regional Cortical Thickness Predicts Top Cognitive Performance in the Elderly

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While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. Prior studies have found that cortical thickness in the cingulate cortex, a region involved in information processing, memory, and attention, distinguish those with exceptional cognitive abilities when compared to their cognitively more typical elderly peers. Others major areas outside of the cingulate, such as the prefrontal cortex and insula, are also key in successful aging well into late age, suggesting that structural properties across a wide range of areas may better explain differences…
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Blood test shows promise for identifying risk for Alzheimer’s symptoms

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A blood test may be able to identify individuals at increased risk for developing Alzheimer’s disease symptoms, according to research presented at the Clinical Trials on Alzheimer’s Disease conference. The results came as part of the AHEAD study. Joshua D. Grill “The goal of this study is to stop Alzheimer’s disease before it begins — delaying or preventing symptoms in people at increased biological risk,” Joshua D. Grill, PhD, recruitment unit co-chair for the Alzheimer’s Clinical Trials Consortium, which helps oversee the AHEAD Study Recruitment and Retention Working Group, told Healio Psychiatry. “The latest advance is to use a blood test to improve the…
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Could Restoring Deep Sleep by Jolting the Brain Ward Off Alzheimer’s?

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Overall, this nice series of experiments identifies yet another component of the sleep/wake regulatory system—the TRN—that is disrupted by Aβ and degenerated in AD. It is interesting that stimulating the TRN can impact Aβ. It is unlikely, however, that the TRN is the only stimulation target necessary, and that stimulating it would address all the sleep disruptions caused by Aβ and also tau pathology. AD pathophysiology impacts multiple different systems regulating sleep, including brainstem and hypothalamic nuclei, cortical nodes regulating slow wave expression, and even the hippocampus that regulates ripples, and coupling of slow waves, sleep spindles, and ripples. This…
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Hypertension Medications Which Help Ward off Memory Loss

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Drs. Jean Ho (left) and Daniel Nation (right)Photo: Steve Zylius/UCI Continuing all this week, National Public Radio's “Academic Minute” series features a UCI expert. This Friday, tune in to hear Jean K. Ho, postdoctoral scholar at the UCI Institute for Memory Impairments and Neurological Disorders, who studies how hypertension medications help ward off memory loss. Learn More At NPR's Academic Minute: https://www.npr.org/podcasts/564572329/the-academic-minute You Can Also Listen On Apple Podcasts: https://podcasts.apple.com/podcast/1060078714
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A Q&A With Dr. Elizabeth Head On Her Latest Research

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The Women's Alzheimer's Movement - WAM spoke to University of California, Irvine’s Dr. Elizabeth Head about her latest research into the link between #Alzheimers and #DownSyndrome. Learn more about her study funded through the UCI MIND WAM Initiative. WAM: Why are we studying Alzheimer’s disease in people with Down syndrome? Is there a link? Dr. Head: Within the Down syndrome population, 95% of people have a full extra copy of chromosome 21. This chromosome contains a gene that is responsible for making the beta-amyloid protein that clumps together to form amyloid plaques in the brain, which is a hallmark of Alzheimer’s…
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Neuroscientists Find How Associative Memories Are Made

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(Photo : Image from Unsplash Website) Neuroscientists Find How Associative Memories Are Made Neuroscientists have reportedly found how associative memories are made. The ability to be able to remember relationships that are made between unrelated items like odor and location, songs and events, is known as associative memory. The University of California, Irvine's neuroscientists, have reportedly discovered some specific types of neurons within the brain's memory center that are responsible for acquiring brand new associative memories. The findings of the study were reportedly published in the journal Nature, as also seen in news-medical.net. Psychologists reportedly started studying associative memory as…
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Building Inclusive and Open Alzheimer Disease and Alzheimer Disease–Related Dementias Research Programs

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The linked editorial from JAMA Neurology cites IMPACT-AD, the course co-led by UCI MIND, and work by The 90+ Study investigators, Maria Corrada, ScM, ScD and Claudia Kawas, MD. The systematic review by Mooldijk et al1 summarizes multiple areas in which the field of dementia research can improve clinical studies. Our Editorial will focus on ethnic and racial diversity (primarily in the US) and on age differences noted in the systematic review between population-based cohorts and clinical cohorts. We also share new and ongoing efforts in this area from the National Institute on Aging (NIA) and the broader National Institutes of…
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AD Biomarkers & Preclinical Diagnostics Report Now Available

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On June 28–29, 2021, the National Academies of Sciences, Engineering, and Medicine held a virtual workshop, “Behavioral and Social Research and Clinical Practice Implications of Biomarkers and Other Preclinical Diagnostics of Alzheimer's Disease (AD) and AD-Related Dementias” (AD/ADRD). UCI MIND Director Joshua Grill was an invited participant in this meeting, for which a brief report is now available.
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UCI MIND and AlzOC present free online conference on Alzheimer’s disease

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Panel of experts from around the nation to give updates on what is the third leading cause of death in Orange County. UCI MIND and Alzheimer’s Orange County will host a free, virtual conference featuring experts discussing the latest developments in research around Alzheimer’s disease, which is Orange County’s third leading cause of death and afflicts more than 84,000 residents. The 32nd annual conference, “Alzheimer’s From All Angles,” will stream live on YouTube and Facebook on Sept. 10 from 8 a.m. to noon. One particularly timely topic will be what effect a viral disease like COVID-19 can have on brain…
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New genetically modified mouse model mimics multiple aspects of human Alzheimer’s disease

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NIA-supported scientists have developed a new mouse model that produces a form of the human beta-amyloid protein, a hallmark of Alzheimer’s disease. An important research tool, mouse models enable the exploration of genetic, environmental, and behavioral aspects of Alzheimer’s, as well as make it possible to test drug candidates before human studies. The new mouse model, which was reported in a recent article in Nature Communications, can be used by other scientists to advance Alzheimer’s research. Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) MODEL-AD consortium Many factors, including gene changes, the aging process, and conditions in the…
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Aducanumab update

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Contributed by Joshua Grill, PhD and Jason Karlawish, MD UCI MIND Director Joshua Grill, PhD co-authored an article in Nature Reviews Neurology about the FDA's decision on Aduhelm. Read more on this below: Since the FDA approved Aduhelm (aducanumab) on June 7, there has been considerable conversation, debate, and even backlash about the decision. It may seem difficult to keep up. Here is a recap of some of the most recent important events. The FDA granted Aduhelm what is known as “accelerated approval.” This means that the approval did not indicate that the drug has been adequately shown to benefit…
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New Mouse Model Provides 1st Platform to Study Late-Onset Alzheimer’s

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UCI School of Biological Sciences Dean Frank LaFerla is co-senior author of a study involving a new genetically engineered mouse model that, unlike its predecessors, is based on the most common form of Alzheimer’s disease. This could help lead to major strides in the fight to end this deadly disease! Dean LaFerla discusses his findings in a new podcast: https://www.bio.uci.edu/frank-laferla-podcast/
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Swarup Lab research published in Nature Genetics

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Contributed by Vivek Swarup, PhD The brain is made up of billions of cells that are tightly coordinated in complex neural circuitry and are ultimately responsible for manifesting our memories, emotions, and personalities: the very essence of being human. Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative disorders worldwide and results in cognitive decline and memory loss, and we presently do not have effective treatments for AD. There is a pressing need to deepen our understanding of AD, and by studying how individual cells are changing in disease, or identifying those that are resilient to such changes, we…
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A crucial, overlooked question on the new Alzheimer’s drug: When should patients stop taking it?

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In this Nov, 22, 2019, photo, Charles Flagg, who is stricken with Alzheimer's disease, rests his arm during his infusion while participating in a study on the drug Aducanumab at Butler Hospital in Providence, R.I. New results were released on the experimental medicine whose maker claims it can slow the decline of Alzheimer's disease, the most common form of dementia. (AP Photo/Charles Krupa) A crucial, overlooked question on the new Alzheimer’s drug: When should patients stop taking it? STAT News - June 24, 2021 “When we enroll families in studies of treatments like aducanumab, we try to educate them that…
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UCI-led meta-analysis identifies hypertension medications that help ward off memory loss

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People taking drugs that cross the blood-brain barrier experienced less cognitive decline June 21, 2021 The research conducted by Daniel Nation, UCI associate professor of psychological science, and Jean Ho, a postdoctoral scholar at the UCI Institute for Memory Impairments and Neurological Disorders, included more than 12,800 people over the age of 50 in 14 separate studies carried out across six countries. Steve Zylius / UCI Irvine, Calif., June  21, 2021 — A large-scale meta-analysis led by University of California, Irvine researchers provides the strongest evidence yet of which blood pressure medications help slow memory loss in older adults: those that can…
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Furor rages over FDA approval of controversial Alzheimer’s drug

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Marc Archambault, who has early-stage Alzheimer's disease, receives his first dose Wednesday of the newly approved intravenous drug Aduhelm at Butler Hospital in Providence, R.I. (Jessica Rinaldi/Pool/Reuters) “My greatest concern is around people with families with Alzheimer’s disease,” said Joshua D. Grill, an Alzheimer’s researcher at the University of California at Irvine. “Few can afford the financial burden in the first place, let alone the additional costs of Aduhelm.” He said the cost of an amyloid PET scan was at least $5,000. “Doctors, families, even we researchers need more guidance,” Grill said. Spinal taps offer a more affordable way of determining…
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Alzheimer’s treatment study seeks volunteers, including two sites in Portland

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KATU News: “We all have to do more because this is about the most important medical problem we face as a society today," said Dr. Josh Grill, a member of the AHEAD Study leadership team and director of the UC Irvine Institute for Memory Impairments and Neurological Disorders. Grill said his AHEAD Study team is testing a new investigational treatment, examining whether they can slow slow or stop the earliest brain changes due to Alzheimer's disease in people with a higher risk of developing the disease later in life. The team is seeking volunteers on its website: https://www.aheadstudy.org/ "All research…
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Curiosity Is Key for Keeping Your Memory in Top Shape as You Age—Here Are 4 Exercises That Are Better Than Brain Games

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UCI MIND Faculty Member Christine Gall, PhD, a neuroscientist and professor of anatomy and neurobiology at UC Irvine’s School of Medicine, explains that our brains contain specialized cells, or neurons, that are responsible for sending and receiving information. Much like a circuit board in a computer, our brains create networks of neurons that transmit electrical activity when we engage in just about anything. These charges, AKA synapses, are critical for learning and memory.
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Minorities Receive Less Timely Dementia Diagnoses Than Whites

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CHINNAPONG/GETTY IMAGES An accompanying editorial in JAMA Neurology noted that the study apparently is the first to focus on disparities related to “time to diagnosis and comprehensiveness of evaluation” of dementia. Claudia Kawas, M.D., a , geriatric neurologist and researcher at the University of California, Irvine, and other authors of the editorial … point to the need for more diversity in dementia research — particularly as the aging U.S. population grows more diverse.
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UCI MIND faculty member Dr. Tahseen Mozaffar awarded $4.2M grant to study rare muscle disorder affecting aging Americans

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UCI School of Medicine Tahseen Mozaffar, MD, a professor of neurology and director of the Division of Neuromuscular Disorders and the UCI-MDA ALS and Neuromuscular Center at UCI's School of Medicine will lead a study on sporadic inclusion body myositis (sIBM), which affects aging adults causing asymmetric muscle weakness and severe disability. Currently untreatable, sporadic inclusion body myositis (sIBM) causes muscle weakness and severe disability Irvine, CA – April 6, 2021 – The National Institute of Arthritis and Musculoskeletal and Skin Diseases has awarded UCI a 5-year, $4.2 million grant to study sporadic inclusion body myositis (sIBM), which affects aging adults…
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Tracking the Alzheimer’s-Down syndrome connection

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Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS) Award By the time they’re 40, most people with Down syndrome develop beta amyloid plaques in the brain — a key characteristic of Alzheimer’s disease. Scientists believe this is because they have an extra copy of chromosome 21, which carries an amyloid-producing gene. Many people with Down syndrome do develop Alzheimer’s disease, but some manage to avoid the devastating neurodegenerative consequences despite having these plaques in their brains. To learn more about the connection between Down syndrome and Alzheimer’s disease, UCI School of Medicine researchers are spearheading a major international research effort that…
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Why more of us are living to 100

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Carol Robertson, 105, of St. Paul, gets her COVID-19 vaccine on Feb. 4 at a HealthPartners Clinic in Woodbury, Minn. She shows a photo on a phone of herself at a younger age. Courtesy of HealthPartners file On Monday, MPR News host Kerri Miller talked to two researchers, including UCI MIND investigator Claudia Kawas, MD, about what they’re learning about living to be 100. Do you have to win the genetic lottery to live an entire century? Or could research unlock the secret to living longer and living longer well? Listen here >
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Leslie Thompson Tackles Huntington’s Disease One Gene at a Time

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The UCI professor has dedicated her career to finding answers to a rare genetic disease’s most crucial questions. An estimated 30,000 genes make up the human genome, with an individual’s entire uniqueness created by genetic mutations. From tissues and blood as well as distinctive physical features, like eye and hair color to temperament and so much more, genes are the coded instructions for building an entire person. But sometimes those instructions contain errors and genes can mutate to form many different things, including diseases. One such disease, Huntington’s disease, is a rare, inherited disease triggered by a single genetic mutation…
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UCI MIND’s First-Ever Virtual Gala Warms Hearts, Opens Minds, Drives Donations Both On and Offline

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UC Irvine’s Institute for Memory Impairments and Neurological Disorders raised some $300,000 at its A December to Remember Gala on Dec. 5, 2020. The event took place virtually for the very first time, reaching over 850 viewers on multiple online channels including Facebook, Youtube and the UCI MIND website. A recording of the event is available to view on UCI MIND’s YouTube page. The online broadcast, co-hosted by UCI MIND Director Joshua Grill and auctioneer Zack Krone, included performances from Justin Willman, the star and creator of the hit Netflix series “Magic for Humans,” and Ashley Campbell, singer-songwriter and daughter of…
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