Aging in the context of immunological architecture, function and disease outcomes. Andrea L. DiCarlo, Rebecca Fuldner, Joseph Kaminski and Richard Hodes. Trends in Immunology 30: 293-294, 2009.
Aging in the context of immunological architecture, function and disease outcomes. Andrea L. DiCarlo, Rebecca Fuldner, Joseph Kaminski and Richard Hodes. Trends in Immunology 30: 293-294, 2009.
NIA participates in this NIH general initiative, which permits PIs on many different types of research grants to apply for an administrative supplement to support an individual returning to the research workforce after a forced interruption (e.g., raising children or caring for a disabled parent). Trainees and investigators associated with Nathan Shock Centers are eligible to apply for these supplements.
Anyone considering an application under this Program Announcement is strongly encouraged to contact NIA’s Diversity/Re-Entry Supplement Program Coordinator, Dr. Michael-David A.R.R. Kerns, at firstname.lastname@example.org or 301-402-7713 before beginning work on - or submitting - a Diversity or Re-Entry Supplement application.
NIA participates in this NIH-wide supplement program. This program replaces the prior NIH Research Supplements for Under-represented Minorities and Research Supplements for Individuals with Disabilities programs. Trainees or investigators associated with Nathan Shock Centers are eligible to apply for these supplements.
The mutant mouse aging colony is slated to end in September 2013. Old mice will be available until September 2013 but the availability of young mice will end earlier. Entries of different strains into the mutant mouse aging colony will end at different times, dependent on the lifespan and pattern of use of the strain.
The research of Jennifer Manly, PhD, and colleagues at Columbia University suggests that methodological and analytical approaches, not actual racial or ethnic disparities in cognition, may in some cases help explain differences between older African Americans and non-Hispanic whites on cognitive test performance.
The Columbia group's findings, published in the March 2002 Journal of the International Neuropsychological Society, offer a powerful new tool - adjusting test results for quality of education - as one way to make cognitive testing of older people more culturally neutral. In the study, when test scores of participants with similar quality of education, measured by reading level, were compared, differences in test scores between two racial groups mostly disappeared.
The report challenges a standard approach used in research on cognition and dementia. Because differences in education might affect test scores or health status, most studies that have adjusted for the number of years of schooling still found that older African Americans did not score as well on cognitive tests as non-Hispanic whites. Manly's work looks instead at the quality of education. Inequalities in the educational experience of those who grew up in an era of segregated schools, Manly reasons, might be attributed to less funding and resources for such schools as well as fewer days per year that schools in the agrarian South were open for instruction. These discrepancies in early education, Manly suggests, have the potential to persist throughout life, as indicated in differences in reading levels between older African Americans and non-Hispanic whites.
At the NIA, racial and ethnic differences in cognitive function and dementia are an increased focus of research. "Several studies have reported racial and ethnic differences in cognitive performance in older adults and in the prevalence of Alzheimer's disease," notes Molly Wagster, PhD, program director for neuropsychology of aging research and project officer for the Manly study. "Because cultural, educational, or other differences might affect performance on this type of testing, there have been questions about whether measurement techniques are as culturally neutral as they could be."
Participants were drawn from a community-based study of cognitive aging in New York City's ethnically diverse neighborhoods of northern Manhattan. Random sampling was used to select 192 African Americans and 192 non-Hispanic whites age 65 and older. The two groups were matched in age, sex, and number of years of education. Participants were given medical evaluations at the start of the study to confirm that they did not have dementia and that they had no problems with daily activities. A battery of neuropsychological tests was then administered to examine memory, learning, and thinking abilities. Older people with low levels of reading ability could only name letters or read short, common words. Those with higher reading levels were able to pronounce complex, less common words out of context.
The African American group scored lower on the neuropsychological test battery overall as compared to non-Hispanic whites. But when reading scores were factored in, most differences between the groups were no longer statistically significant. The exceptions were category fluency (a test in which people must name objects in a category during a set period of time) and a drawing test, where differences between racial groups were observed even after adjusting for reading level. More information is needed to explain the persistent differences on those two measures, the researchers said.
Manly recommended further research to sort out methodological and analytical approaches, such as accounting for quality of education, from real racial or ethnic disparities in cognitive test performance. Such problems in methodology and analysis make it difficult to establish whether one group or another truly may have greater rates of cognitive decline and dementia in minority groups. "We need to develop measures designed to assess cognitive abilities in a way that is compatible with African American and other cultures," she notes. "With these, we will have greater confidence in any measures which show - or do not show - differences in cognitive health and dementia among various groups. Dr. Manly pursues such research as a neuropsychologist at the NIA-supported Alzheimer's Disease Center at Columbia University. Part of Dr. Manly's focus at the Center concentrates on research to improve the accuracy in diagnosing cognitive impairment and decline over time.
Researchers at Columbia are now adding tests of reading levels to their assessments of cognitive ability and are looking to see how accounting for quality of education might affect previous findings on levels of cognitive performance and rates of dementia among different groups in the community. In addition, Manly and her colleagues are carrying out further research on the effect of quality of education and literacy among Spanish-speaking Caribbean Hispanics through a pilot grant from the Columbia Center for the Active Life of Minority Elders (CALME), a Resource Center for Minority Aging Research (RCMAR) funded by the NIA and the National Institute of Nursing Research.
Genetics may influence memory performance in families with a history of Alzheimer’s Disease according to researchers writing in the February 10, 2004 issue of Neurology. Previous human genetic studies focusing on memory have been limited primarily to twin studies. In this new study, NIA-supported grantees at Columbia University, Joseph Lee, DrPH, and Richard Mayeux, MD, MSc, examined the heritability of cognitive elements, including memory, in patients with AD and their family members across multiple generations. Their study included data from 1,036 individuals from 266 Caribbean Hispanic families from the Dominican Republic and Puerto Rico.
Neuropsychological tests were given to all family members and those with AD, in Spanish. Study participants were tested for memory, attention, abstract reasoning, language, and visual-spatial ability.
Researchers found that nearly 50 percent of assorted memory abilities among study participants were due to genetics, while the other half can be attributed to outside factors, such as education. Because traits, such as the genetic mutation that triggers early-onset AD, are dominant, memory performance may have an even higher genetic influence than the test results suggest.
Areas of mental ability that appear to be less influenced by genetics included attention, abstract reasoning, language, and visual-spatial ability. Even after the scores of those participants with AD were removed from analysis, researchers arrived at the same conclusions regarding memory performance. When adjustments for sex, age, education, and general intelligence were made, heritability approximations increased for cognitive tests, especially for those observed for memory. No other cognitive ability was estimated to be as closely linked to genetics as memory.
The relationship between the apolipoprotein E gene (APOE) and the risk of developing AD was tested. The g4 variant allele of APOE is strongly associated with AD. The APOE gene, however, appeared to have little influence on memory scores. When researchers controlled for the APOE gene, heritability estimates changed modestly with a slight increase in delayed recall; however, estimates made little to no changes for other memory scores.
More research is needed to establish whether these findings apply to families without multiple family members with AD and those living in the U.S. Because those who lived in the Dominican Republic received limited education between the years 1930 to 1961, the average education of those researched from this area is 6 years. Past research suggests that this group may be more susceptible to AD than those educated in the U.S., because education appears to have AD protective effects. A better grasp of which genetic influences affect memory and memory impairment in AD may shed light on which genetic factors cause this degenerative disease.
The Alzheimer’s Disease Neuroimaging Initiative (ADNI)—a project developed by the National Institutes of Health (NIH)—is seeking 800 older adults to participate in a study aimed at identifying biological markers of memory decline and AD. Ultimately, scientists hope that brain and biological changes can be detected before memory decline and other symptoms appear, allowing the effectiveness of drugs to be evaluated at the earliest possible time.
The $60 million, 5-year ADNI study is the most comprehensive effort to date to identify brain and other biological changes associated with memory decline. The project was begun by NIA and is supported by more than a dozen other Federal agencies and private-sector companies and organizations. Investigators at 58 local study sites across the U.S. and Canada will be asking people ages 55 to 90 to become a part of this landmark research.
“We encourage people to participate in this important study because it will help us to identify needed biological markers of memory decline and Alzheimer’s disease. These biomarkers could become comparable to the cholesterol measures now used as biomarkers for heart disease,” says Susan Molchan, M.D., program director for the ADNI project at the NIA. “In addition, using what we learn from the brain scans and other tests, we hope to lessen the time and cost of testing drugs and to bring treatments to patients much sooner.”
Scientists are looking for new ways to measure changes in the brain that occur with normal aging and with the progression of mild cognitive impairment (MCI), a subtle but measurable transitional state between the cognitive changes of normal aging and very early AD. People with MCI have memory impairments but otherwise function well and do not meet clinical criteria for dementia.
The ADNI researchers will employ serial magnetic resonance imaging (MRI); positron emission tomography (PET) scans; measurement of various biological compounds in blood, cerebrospinal fluid, and urine; and clinical and neuropsychological assessments to track MCI and early AD progression. MRI and PET scans are used in both medical practice and research to produce images of the brain.
The study’s principal investigator (PI) is neuroimaging expert Michael W. Weiner, M.D., of the San Francisco Veterans Affairs Medical Center and the University of California, San Francisco. The Northern California Institute for Research and Education, a foundation affiliated with the U.S. Department of Veterans Affairs, has been awarded the multi-center ADNI grant.
Dr. Weiner explains that the 800 adults ages 55 to 90 sought for the study will be divided into three groups: approximately 200 cognitively normal older people will be followed for 3 years, 400 people with MCI will be followed for 3 years, and 200 people with early AD will be followed for 2 years. At the end of the study, the researchers will compare neuroimaging, biological, and clinical information from the participants, looking for correlations among the data to develop standards for tracking progression of memory decline.
A unique feature of the project is the development of an imaging and biomarker database that can be tapped by researchers in both the public and private sectors as they develop and test drugs for memory decline.
A special aspect of the project is the support of Dr. Maya Angelou, the eminent poet, author, educator, and historian. Dr. Angelou, a professor at Wake Forest University in Winston-Salem, NC, is working with the researchers to ask the public to take part in the study through the national ADNI recruitment outreach campaign, “Imagine Stopping the Progression of Alzheimer’s Disease,” in which she will appear in radio and print public service announcements. She has a number of dear friends who have suffered the effects of AD.
ADNI is the largest public-private partnership on brain research underway at the NIH, part of the U.S. Department of Health and Human Services (DHHS). In addition to the NIA, the Federal ADNI partners are the National Institute of Biomedical Imaging and Bioengineering, also part of NIH, and the U.S. Food and Drug Administration, another DHHS agency.
Partnership with private-sector funders is managed through the not-for-profit Foundation for the NIH, established by the U.S. Congress to support NIH’s mission by facilitating private-sector organizations’ support of and involvement with NIH programs. Corporate and nonprofit participants are: Pfizer Inc; Wyeth Research; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Merck & Co., Inc.; AstraZeneca AB; Novartis Pharmaceuticals Corporation; Eisai Global Clinical Development; the Alzheimer’s Association; Elan Corporation, plc; and the Institute for the Study of Aging.
The NIA’s lead program for AD research—the Neuroscience and Neuropsychology of Aging (NNA) Program—recently welcomed three new health science administrators (HSAs). Each new staff member brings a wealth of scientific and administrative expertise to the NNA as the program continues to foster a variety of research programs exploring the normal course of aging in the neuronal system and the dementias of aging.
“We are delighted to welcome Nina Silverberg, Ph.D., Laurie Ryan, Ph.D., and Suzana Petanceska, Ph.D. They have impressive research experience and excellent science administration skills. We have truly strengthened our abilities to serve the scientific community and continue the quest to find the causes of age-related cognitive, motor, and sensory decline and of dementias such as AD,” said Marcelle Morrison-Bogorad, Ph.D., Director, NNA.
As the Assistant Program Director for the Alzheimer’s Disease Centers (ADCs), Dr. Silverberg will be responsible for assisting Dr. Creighton (Tony) Phelps with the Centers. Specifically, she will be involved with cognitive assessment in normal aging and dementia, education cores, and minority outreach programs in the ADCs.
Dr. Silverberg received her Ph.D. from the University of Arizona and was most recently a clinical research scientist at the Sun Health Research Institute (Arizona ADC). At the ADC, she was involved in grant development and extracting and analyzing data from the brain donation program database. Dr. Silverberg also coordinated the ADC’s American Indian outreach program. She was the principal investigator on a New Investigator Research Grant from the Alzheimer’s Association to assess the usefulness of culturally adjusted neuropsychological tools in an American Indian population. She worked closely with a neurologist and neuropsychologist in designing, carrying out, analyzing, and interpreting various investigations of AD, mild cognitive impairment (MCI), Parkinson’s disease, and normal aging.
Dr. Petanceska is a new HSA whose portfolio spans the Neurobiology of Aging and the Dementias of Aging branches at NNA. Her duties are to manage and develop a portfolio of grants addressing aspects of normal aging related to AD pathogenesis and to assist in developing the NNA’s translational initiatives.
Dr. Petanceska received her Ph.D. from the Sackler Institute for Graduate Biomedical Studies at New York University. Prior to coming to NNA, Dr. Petanceska was an Assistant Professor of Psychiatry and Pharmacology at the Nathan Kline Institute/New York University. She has extensive research experience in AD pathogenesis and has had a long-standing interest in AD therapeutics. Her most recent research focused on the role of disrupted sterol metabolism in the development of AD amyloidosis and the mechanisms by which estrogens and cholesterol-lowering drugs might exert neuroprotection.
Dr. Ryan will be involved in the AD clinical trials program, which includes managing current AD clinical trials and further developing the clinical trials program by identifying goals, research questions, and appropriate investigators. She will also be responsible for helping to stimulate research in the clinical trials portfolio, including pilot and large-scale clinical trials for AD treatment, modification of disease progression, and prevention.
Dr. Ryan received her Ph.D. in clinical psychology with specialty training in neuropsychology at Louisiana State University in Baton Rouge. Her professional interests as a neuro-psychologist center on the neurocognitive and behavioral manifestations of disorders affecting central nervous system function such as AD and traumatic brain injury. She was most recently the Assistant Director for Research and Senior Neuropsychologist for the Defense and Veterans Brain Injury Center, Department of Neurology, at the Walter Reed Army Medical Center in Washington, DC, where she was responsible for overseeing clinical research development and implementation in particular clinical trials. Dr. Ryan has also served as an Assistant Professor of Neurology, Uniformed Services University of the Health Sciences in Bethesda, Maryland.
The Alzheimer's disease (AD) research community lost a legendary figure and guiding light on September 16, 2008, when Dr. Robert Katzman, 82, died at his home in La Jolla, CA, after a long illness. He was professor emeritus of neurosciences and former chair of the Department of Neurosciences at the University of California San Diego School of Medicine. From 1964 to 1984, he was chair of neurology at the Albert Einstein College of Medicine in New York. He retired from UC San Diego in 2002.
Dr. Katzman was founding director of the NIA-funded Shiley-Marcos Alzheimer's Disease Research Center at UC San Diego, one of the original members of the NIA's National Advisory Council on Aging, and a founder of the Alzheimer's Association.
Before Dr. Katzman's work on AD began in the 1960s, little time and money were spent on AD research and therapy. Many researchers and clinicians regarded AD as an interesting but rare form of "presenile dementia," mainly occurring in people under age 65. They believed that dementia in people over 65, termed "senile dementia," is mainly a product of aging, not disease. Some of these beliefs echoed the early conclusions of Dr. Alois Alzheimer, the German scientist who originally described AD in 1906.
Dr. Katzman and his longtime collaborator, Dr. Robert Terry, changed these mistaken notions. During 3 decades of work, they demonstrated that most cases diagnosed as senile dementia were, in fact, AD. These findings redefined AD as a "major killer" and mounting public health threat.
In 1976, Dr. Katzman published a landmark editorial, The Prevalence and Malignancy of Alzheimer's Disease, in Archives of Neurology. In 1977, Drs. Katzman and Terry organized the first national conference on AD, sponsored in part by the NIA. These efforts led to a boom in basic research and clinical trials on AD.
"We owe Dr. Katzman a tremendous debt of gratitude," said NIA Director Dr. Richard Hodes. "He performed groundbreaking research and provided spirited advocacy on Alzheimer's disease. His accomplishments helped to realign attitudes about Alzheimer's, clarify its pervasiveness, and substantially increase the attention paid to this disease by scientists, clinicians, funding organizations, and the public."
Dr. Katzman received many accolades and awards during his career. Among these was the prestigious Potamkin Prize for Research in Pick's, Alzheimer's, and Related Diseases, awarded in 1994 by the American Academy of Neurology.
Dr. Claudia Kawas, University of California, Irvine, a long-time colleague, adds: "Dr. Katzman was known for his integrity, his generosity and his leadership. As a mentor and friend, he inspired and influenced the careers of many who continue in the fight against Alzheimer's disease. The gap he leaves in the field of Alzheimer's disease, and personally for his many family, friends and colleagues, will be profound."
A recent study by researchers from the Texas Tech University Health Science Center and the Mayo Clinic Department of Medicine shows that raising the Mini-Mental State Examination (MMSE, a standard screening tool for dementia) "cut score" for more highly educated people increases the early accuracy of results for this group. Earlier identification of cognitive decline could aid in their treatment.
Scores on the MMSE decrease with advanced age and less education. The standard MMSE cut score is 24, meaning that a score of 23 or below indicates possible dementia. However, a review of data for 4,248 people, including 1,141 with 16 or more years of education, suggests that a more appropriate cut score for college-educated individuals is 27. Raising the MMSE cut score for this group to 27 increased the accuracy of the classification rate from 89 to 90 percent and provided an "optimal balance" of sensitivity and specificity, the study results reveal. A cut score of 27 identified 70 of the 104 college-educated patients with dementia who were missed when a cut score of 24 was used.
The researchers conclude that older, more highly educated patients who complain of cognitive decline and score below 27 on the MMSE should be referred for a comprehensive dementia evaluation.
O'Bryant, S.E., et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008 July. 65(7):963-67.