• July 16, 2004

    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.

  • January 15, 2006

    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.

  • January 15, 2006

    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.

  • April 15, 2009

    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."

  • April 15, 2009

    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.

  • April 15, 2009

    People with increased levels of tau protein in their CSF develop late-onset AD at earlier ages than do others with the disease, according to a study by researchers at the Washington University School of Medicine in St. Louis. The levels of this protein in CSF may provide a potential biomarker to identify people who may develop AD sooner than others do. The levels of both beta-amyloid and tau—two proteins whose abnormalities characterize AD—in CSF vary widely in individuals with the disease.

    The investigators used genotyping to pinpoint the association between MAPT, the gene that encodes tau, and AD. They found four genetic variants of MAPT that were associated with higher levels of tau, but the higher tau levels were found only in the presence of beta-amyloid deposits. The researchers also confirmed that the genetic variants of MAPT influenced the age at onset of AD clinical symptoms but had no effect on the overall risk of developing AD.

    The results indicate that beta-amyloid deposition leads to MAPT gene expression, which in turn raises tau levels and increases early neurodegeneration in late-onset AD.


    Kauwe, J.S., et al. Variation of MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. Proc Natl Acad Sci USA. 2008 Jun 10. 105(23):8050-54.

  • April 15, 2009

    Previous studies have suggested that frailty, a common but poorly understood condition in older people, may predict the development of dementia. In this study, Rush University researchers examined 165 physically frail older adults before and after their deaths to investigate this connection. First, participants' frailty was evaluated by measuring their grip strength, timed walk, body composition, and fatigue. After death (at a mean age of 88.1 years), their brains were autopsied for evidence of AD, cerebral infarcts, and Lewy body disease.

    Regression analyses controlling for age, chronic diseases, medications, and other factors showed an association between levels of frailty and of AD pathology but no association between frailty and cerebral infarcts or Lewy body disease. A higher level of AD pathology was associated with a higher level of frailty. The link was similar in people with and without dementia.

    The researchers speculate that AD pathology may contribute to frailty by affecting parts of the brain that control movement. Or, AD and frailty may share a common cause. "These different mechanisms are not mutually exclusive and underscore the need for further studies of the relationship between AD and frailty," they conclude.


    Buchman, A.S., et al. Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology. 2008. 71:499-504.

  • April 15, 2009

    Examination of people at risk for the rare familial form of AD may provide clues to how the disease develops in others—years before clinical symptoms appear, according to a recent study. The clues are levels of certain proteins found in plasma and cerebrospinal fluid (CSF), biomarkers that might be used to diagnose AD in its earliest preclinical stage.

    The research team, led by scientists at the University of California, Los Angeles, examined blood and CSF samples from 21 adults under age 50, most of whom had no symptoms of AD but were related to people with familial AD, a genetically inherited form of the disease. One of their biomarkers, elevated levels of plasma Aß42 (a type of beta-amyloid protein), also has been found in people with late-onset AD.

    The results confirmed and amplified what previous studies have shown: Pre-symptomatic people with the familial-AD mutation had higher levels of plasma Aß42, which declined as the disease progressed, as well as higher plasma Aß42/Aß40 ratios, than those in people without the mutation. People with the mutation had lower CSF Aß42/Aß40 ratios and higher levels of CSF tau and p-tau181 than people who did not carry the mutation. There was no significant difference between the two groups in plasma F2-isoprostane levels.


    Ringman, J.M., et al. Biochemical markers in persons with preclinical familial Alzheimer disease. Neurology. 2008 July. 71:85-92.

  • April 15, 2009

    Receiving a diagnosis of dementia does not prompt a strong negative reaction in most people and may even provide relief because it explains symptoms and makes patients feel less helpless, concludes a recent study.

    To gauge psychological reactions to a dementia diagnosis, researchers from Washington University in St. Louis conducted telephone interviews with patients a few days after they received a dementia diagnosis. Two tests were used: the Geriatric Depression Scale and the "State" version of the State-Trait Anxiety Inventory. Both patients and their companions took the tests. Baseline scores were obtained through comprehensive physical and neurological examinations. Of 90 study participants, 41 were diagnosed with very mild dementia, 21 with mild dementia, and 28 with no dementia.

    The researchers found no significant increase in depression in individuals or their companions, regardless of diagnostic outcome or dementia severity. The level of anxiety also did not increase—and decreased significantly in some cases.


    Carpenter, B.D., et al. Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment. J Am Geriatr Soc. 2008. 56:405-12.

    More information for health care professionals about communicating with older patients is provided in the NIA publication Talking With Your Older Patient: A Clinician's Handbook.

  • April 15, 2009

    A combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) can more accurately detect mild cognitive impairment (MCI) brain abnormalities in the early stages of their development than can either method used alone, a recent study finds. Early diagnosis of amnestic MCI is important because the condition is often a precursor to Alzheimer's disease (AD).

    The researchers, from the National Institute on Aging (NIA) and the University of Pennsylvania, examined MRI and PET images from 30 elderly participants in NIA's Baltimore Longitudinal Study of Aging to distinguish people with aMCI from people who were aging normally. They looked at spatial patterns of brain atrophy and reduced blood flow in dozens of regions of the brain.

    MRI data alone produced an 87 percent accuracy rate for aMCI diagnosis, and PET data alone produced a 50 percent accuracy rate. However, when the two were combined, researchers obtained a 90 to 100 percent accuracy rate—"an excellent diagnostic value" for this method.


    Fan Y., et al. Structural and functional biomarkers of prodromal Alzheimer's disease: a high-dimensional pattern classification study. Neuroimage. 2008. 41:277-85.