In the most comprehensive study to date, neurologists have clearly identified significant differences in the ways that Alzheimer's disease (AD) affects patients with and without the apolipoprotein E ε4 gene (APOE ε4), a known genetic risk factor for the neurodegenerative disease, using a combination of cognitive and neuroanatomic measures. The study found that this gene influences the way the disease manifests, even at its mildest clinical stages.
Study highlights include:
-- Patients with mild AD who carry the ε4 form of the APOE gene perform more poorly on memory tests and have more prominent abnormalities in brain regions critical for memory, compared with patients without this gene variant.
-- In contrast, patients with mild AD who do not have the APOE ε4 gene perform more poorly on tests of attention, language, and executive function and have more prominent abnormalities in brain regions critical for these abilities, compared to patients with APOE ε4.
"These findings have important implications for how we diagnose, treat and follow patients with Alzheimer's Disease," said David Wolk, MD, assistant professor of Neurology at the Penn Memory Center and lead author on the study. "Genetic factors, like the APOE gene, seem to result in somewhat different patterns of cognitive impairment the degree to which memory or attention is affected and the brain regions vulnerable to the disease process."
Both APOE ε4 carriers and non-carriers displayed impaired memory in the study, but in qualitatively different ways. Researchers note that a variety of types of cognitive tests tasks looking at memory, language, attention, and executive function are necessary to make an early diagnosis and monitor of the progression of AD effectively. So far, the emphasis for early diagnosis and monitoring of AD has largely been on memory tests.
The study appears in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).
Using data collected from the Alzheimer's Disease Neuroimaging Initiative, a large multi-center North American study of possible biomarkers for AD, neurologists from the Penn Memory Center at the University of Pennsylvania School of Medicine and the Massachusetts Alzheimer's Disease Research Center at Massachusetts General Hospital (MGH) and Harvard Medical School(HMS) examined how the presence or absence of the ε4 form of APOE influences cognitive function and brain anatomy measured from MRI scans.
Studying participants diagnosed with mild AD, the researchers compared the differences in cognition and in regional cortical atrophy of 67 APOE ε4 carriers with those of 24 non-carriers. Results from a biomarker test of cerebral spinal fluid, developed and previously reported by Penn Medicine researchers, was used to confirm with high diagnostic accuracy that patients included in the study had a molecular profile consistent with AD.
"A few recent clinical trials reported differences in the way patients responded to the drugs being tested depending on whether or not they carried the ε4 allele, which have prompted groups to study these populations independently," said senior author Bradford C. Dickerson, MD, associate professor of Neurology at MGH and HMS. "Rather than restricting trials exclusively to patients with or without APOE ε4, the results from this paper suggest that different behavioral and brain measures, dependent on participants' genotype, might be a useful approach to consider in evaluating investigational drugs."
Ultimately, a personalized medicine approach may factor an individual's genetic status in when considering how to diagnose and monitor the disease.
The ADNI public-private partnership includes federal support from the National Institute on Aging and the National Institute for Biomedical Imaging and Bioengineering, both part of the National Institutes of Health, and the participation of the Food and Drug Administration. Private sector support comes from pharmaceutical companies and other organizations through the Foundation for NIH, which has raised more than $25 million from both corporations and non-profits toward ADNI. Current private sector funders include Abbott Laboratories, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, General Electric Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Inc., Merck & Co., Inc., Novartis AG, Pfizer Inc, F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., and Wyeth Research, as well as non-profit partners the Alzheimer's Association and the Institute for the Study of Aging.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.
Penn's School of Medicine is currently ranked #3 in U.S. News & World Report's survey of research-oriented medical schools, and is consistently among the nation's top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.
Penn Medicine's patient care facilities include:
-- The Hospital of the University of Pennsylvania the nation's first teaching hospital, recognized as one of the nation's top 10 hospitals by U.S. News & World Report.
-- Penn Presbyterian Medical Center named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.
-- Pennsylvania Hospital the nation's first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.
Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2008, Penn Medicine provided $282 million to benefit our community.
Source: University of Pennsylvania School of Medicine
Wednesday, 19 May 2010
Tuesday, 4 May 2010
The International Congress Of Alzheimer's Disease Accepts Four Scientific Presentations By Power3
Power3 Medical Products, Inc. announced that four abstracts were accepted for presentation to the annual meeting of the International Congress of Alzheimer's Disease on July 12, 2010 in Honolulu, Hawaii. The presentations will cover results from protein biomarker discovery, drug response, test development, and ongoing clinical validation trials of the NuroPro® AD biomarkers and blood test for Alzheimer's disease. The four studies to be presented involve a total of 154 Alzheimer's disease patients and 91 Parkinson's disease patients, as well as 210 age-matched normal control individuals and 173 disease control individuals.
The NuroPro® AD biomarkers and blood test are intended to help clinicians distinguish patients with Alzheimer's disease from "normal" individuals, i.e., patients with similar, non-Alzheimer's neurological disorders. They are also intended to solve the critical challenge facing physicians, clinicians, patients and drug developers, who all need tests for early stage accurate and specific diagnosis of this debilitating disease, as well as more guidance for drug therapy, patient selection for drug clinical trials, and better tools to monitor drug treatment response.
The abstracts report the use of combined results from ongoing clinical validation trials of NuroPro® AD. The trials are being conducted by the Power3 scientific team, led by scientific advisory board member Lourdes R. Bosquez, MD and Chief Scientific Officer, Ira L. Goldknopf, Ph.D. in collaboration with Marwan Sabbagh, MD, director of the Banner Sun Health Research Institute. The team is also utilizing previous studies Power3 conducted with Stanley H. Appel, MD during his tenure as Chairman of Neurology at the Baylor College of Medicine and, currently, as Co-Director of the Methodist Neurological Research Institute. Dr. Appel continues to be chairman of the scientific advisory board of Power3.
"These 4 posters represent the culmination of 7 years of hard scientific effort which we have been blessed to pursue with our distinguished collaborators," said Dr. Goldknopf. "There will be some surprises for our colleagues at ICAD that we are particularly excited about because they have the potential to guide us towards improvements in treatment for this awful illness." Dr. Goldknopf will present two of the posters at ICAD, one on NuroPro® AD biomarkers for Alzheimer's specific diagnosis and the other on NuroPro® AD diagnostic clinical validation trials. Dr. Sabbagh will present a third poster on prospective clinical validation of the use of protein biomarkers from newly drawn patient sera for diagnosis of Alzheimer's disease, and Dr. Bosquez will present a fourth poster on NuroPro® AD protein biomarkers and drug response.
"We are proud that Dr. Goldknopf will be joined this year by two members of our scientific advisory board, Dr. Sabbagh and Dr. Bosquez, in presenting to ICAD 2010," said Helen R. Park, MS, Chief Executive Officer of Power3. "For us to present four posters at the same time at such a prestigious forum speaks to the depth of our science and our commitment to improving the outcomes for patients with Alzheimer's disease. This work, in conjunction with the recent filing of our joint patent application with StemTroniX, bodes well for the upcoming acquisition of StemTroniX by Power3."
Source
StemTroniX, Inc.
The NuroPro® AD biomarkers and blood test are intended to help clinicians distinguish patients with Alzheimer's disease from "normal" individuals, i.e., patients with similar, non-Alzheimer's neurological disorders. They are also intended to solve the critical challenge facing physicians, clinicians, patients and drug developers, who all need tests for early stage accurate and specific diagnosis of this debilitating disease, as well as more guidance for drug therapy, patient selection for drug clinical trials, and better tools to monitor drug treatment response.
The abstracts report the use of combined results from ongoing clinical validation trials of NuroPro® AD. The trials are being conducted by the Power3 scientific team, led by scientific advisory board member Lourdes R. Bosquez, MD and Chief Scientific Officer, Ira L. Goldknopf, Ph.D. in collaboration with Marwan Sabbagh, MD, director of the Banner Sun Health Research Institute. The team is also utilizing previous studies Power3 conducted with Stanley H. Appel, MD during his tenure as Chairman of Neurology at the Baylor College of Medicine and, currently, as Co-Director of the Methodist Neurological Research Institute. Dr. Appel continues to be chairman of the scientific advisory board of Power3.
"These 4 posters represent the culmination of 7 years of hard scientific effort which we have been blessed to pursue with our distinguished collaborators," said Dr. Goldknopf. "There will be some surprises for our colleagues at ICAD that we are particularly excited about because they have the potential to guide us towards improvements in treatment for this awful illness." Dr. Goldknopf will present two of the posters at ICAD, one on NuroPro® AD biomarkers for Alzheimer's specific diagnosis and the other on NuroPro® AD diagnostic clinical validation trials. Dr. Sabbagh will present a third poster on prospective clinical validation of the use of protein biomarkers from newly drawn patient sera for diagnosis of Alzheimer's disease, and Dr. Bosquez will present a fourth poster on NuroPro® AD protein biomarkers and drug response.
"We are proud that Dr. Goldknopf will be joined this year by two members of our scientific advisory board, Dr. Sabbagh and Dr. Bosquez, in presenting to ICAD 2010," said Helen R. Park, MS, Chief Executive Officer of Power3. "For us to present four posters at the same time at such a prestigious forum speaks to the depth of our science and our commitment to improving the outcomes for patients with Alzheimer's disease. This work, in conjunction with the recent filing of our joint patent application with StemTroniX, bodes well for the upcoming acquisition of StemTroniX by Power3."
Source
StemTroniX, Inc.
Monday, 3 May 2010
Alzheimer's Memory Problems Originate With Protein Clumps Floating In The Brain, Not Amyloid Plaques
Using a new mouse model of Alzheimer's disease, researchers at Mount Sinai School of Medicine have found that Alzheimer's pathology originates in Amyloid-Beta (Abeta) oligomers in the brain, rather than the amyloid plaques previously thought by many researchers to cause the disease.
The study, which was supported by the "Oligomer Research Consortium" of the Cure Alzheimer Fund and a MERIT Award from the Veterans Administration, appears in the journal Annals of Neurology.
"The buildup of amyloid plaques was described over 100 years ago and has received the bulk of the attention in Alzheimer's pathology," said lead author Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer's Disease Research Center, Mount Sinai School of Medicine. "But there has been a longstanding debate over whether plaques are toxic, protective, or inert."
Several research groups had previously proposed that rather than plaques, floating clumps of amyloid (called oligomers) are the key components that impede brain cell function in Alzheimer's patients. To study this, the Mount Sinai team developed a mouse that forms only these oligomers, and never any plaques, throughout their lives.
The researchers found that the mice that never develop plaques were just as impaired by the disease as mice with both plaques and oligomers. Moreover, when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before.
"These findings may enable the development of neuroimaging agents and drugs that visualize or detoxify oligomers," said Dr. Gandy. "New neuroimaging agents that could monitor changes in Abeta oligomer presence would be a major advance. Innovative neuroimaging agents that will allow visualization of brain oligomer accumulation, in tandem with careful clinical observations, could lead to breakthroughs in managing, slowing, stopping or even preventing Alzheimer's.
"This is especially important in light of research reported in March showing that 70 weeks of infusion of the Abeta immunotherapeutic Bapineuzumab® cleared away 25 percent of the Abeta plaque, yet no clinical benefit was evident."
The Mount Sinai team included Michelle Ehrlich, MD, Professor of Pediatrics, Neurology, and Genetics and Genomic Sciences, and John Steele, a Mount Sinai graduate student, who performed the key analyses of the behavioral data. Dr. Charles Glabe, an oligomer expert and a member of the Cure Alzheimer Fund research consortium, is also a co-author of the paper. Dr Gandy is also a neurologist at the James J Peters Veterans Affairs Medical Center, an affiliate of Mount Sinai School of Medicine.
Source
The Mount Sinai Medical Center
The study, which was supported by the "Oligomer Research Consortium" of the Cure Alzheimer Fund and a MERIT Award from the Veterans Administration, appears in the journal Annals of Neurology.
"The buildup of amyloid plaques was described over 100 years ago and has received the bulk of the attention in Alzheimer's pathology," said lead author Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer's Disease Research Center, Mount Sinai School of Medicine. "But there has been a longstanding debate over whether plaques are toxic, protective, or inert."
Several research groups had previously proposed that rather than plaques, floating clumps of amyloid (called oligomers) are the key components that impede brain cell function in Alzheimer's patients. To study this, the Mount Sinai team developed a mouse that forms only these oligomers, and never any plaques, throughout their lives.
The researchers found that the mice that never develop plaques were just as impaired by the disease as mice with both plaques and oligomers. Moreover, when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before.
"These findings may enable the development of neuroimaging agents and drugs that visualize or detoxify oligomers," said Dr. Gandy. "New neuroimaging agents that could monitor changes in Abeta oligomer presence would be a major advance. Innovative neuroimaging agents that will allow visualization of brain oligomer accumulation, in tandem with careful clinical observations, could lead to breakthroughs in managing, slowing, stopping or even preventing Alzheimer's.
"This is especially important in light of research reported in March showing that 70 weeks of infusion of the Abeta immunotherapeutic Bapineuzumab® cleared away 25 percent of the Abeta plaque, yet no clinical benefit was evident."
The Mount Sinai team included Michelle Ehrlich, MD, Professor of Pediatrics, Neurology, and Genetics and Genomic Sciences, and John Steele, a Mount Sinai graduate student, who performed the key analyses of the behavioral data. Dr. Charles Glabe, an oligomer expert and a member of the Cure Alzheimer Fund research consortium, is also a co-author of the paper. Dr Gandy is also a neurologist at the James J Peters Veterans Affairs Medical Center, an affiliate of Mount Sinai School of Medicine.
Source
The Mount Sinai Medical Center
Insufficient Evidence To Support Preventive Measures For Alzheimer's Disease
Many preventive measures for cognitive decline and for preventing Alzheimer's disease - mental stimulation, exercise, and a variety of dietary supplements - have been studied over the years. However, an independent panel convened this week by the National Institutes of Health determined that the value of these strategies for delaying the onset and/or reducing the severity of decline or disease hasn't been demonstrated in rigorous studies.
"Alzheimer's disease is a feared and heart-breaking disease," said Dr. Martha L. Daviglus, conference panel chair and professor of preventive medicine and medicine at Northwestern University, Chicago. "We wish we could tell people that taking a pill or doing a puzzle every day would prevent this terrible disease, but current evidence doesn't support this."
The panel's assessment of the available evidence revealed that progress to understand how the onset of these conditions might be delayed or prevented is limited by inconsistent definitions of what constitutes Alzheimer's disease and cognitive decline. Other factors include incomplete understanding of the natural history of the disease and limited understanding of the aging process in general. The panel recommended that the research community and clinicians collaborate to develop, test, and uniformly adopt objective measures of baseline cognitive function and changes over time.
Although many non-modifiable risk factors have been examined, age is the strongest known risk factor for Alzheimer's disease. Additionally, a genetic variant of a cholesterol-ferrying protein (apolipoprotein E), has strong evidence of association with the risk for developing Alzheimer's disease. Although it is hoped that improved understanding of genetic risk factors may ultimately lead to effective therapies, currently these associations are primarily useful in the clinical research setting.
The panel determined that there is currently no evidence of even moderate scientific quality supporting the association of any modifiable factor - dietary supplement intake, use of prescription or non-prescription drugs, diet, exercise, and social engagement - with reduced risk of Alzheimer's disease. The evidence surrounding risk reduction for cognitive decline is similarly limited. Low-grade evidence shows weak associations between many lifestyle choices and reduced risk of Alzheimer's disease and cognitive decline.
Although there is little evidence that these interventions lessen cognitive decline, some are not necessarily harmful and may confer other benefits. However, the panel also emphasized the need for enhanced public understanding that these proposed prevention strategies are currently, at best, only loosely associated with improved outcomes. This means that carefully-designed randomized studies may reveal that these modifiable factors enhance, detract, or have no effect on preventing Alzheimer's disease and cognitive decline.
"These associations are examples of the classic chicken or the egg quandary. Are people able to stay mentally sharp over time because they are physically active and socially engaged or are they simply more likely to stay physically active and socially engaged because they are mentally sharp?" added Dr. Daviglus. "An association only tells us that these things are related, not that one causes the other."
The panel found that certain chronic diseases, such as diabetes and depression, and risk factors such as smoking are associated with increased risk of both Alzheimer's disease and cognitive decline. However, studies have not yet demonstrated that these medical or lifestyle factors actually cause or prevent Alzheimer's disease or cognitive decline, only that they are related.
There is insufficient evidence to support the use of pharmaceuticals or dietary supplements to prevent Alzheimer's disease or cognitive decline. Ongoing studies exploring factors including but not limited to physical activity, omega-3 fatty acids (typically found in fish), antihypertensive medications, and cognitive engagement may provide new insight into Alzheimer's disease and cognitive decline prevention.
The panel made a variety of recommendations to shape the future research agenda and fill identified gaps, while acknowledging that advancing our understanding of these complex conditions in order to develop conclusive, evidence-based prevention recommendations will require considerable time and resources. For example, the panel advocated launching long-term, longitudinal studies to better characterize the natural history and progression of these diseases in the community. They also recommended the establishment of registries for Alzheimer's disease and cognitive decline, modeled on existing registries for cancer.
Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. There are numerous ongoing or planned investigations which may offer promising new insights regarding the causes and prevention of these diseases.
An updated version of the panel's draft consensus statement, which incorporates comments received during the public session, are posted at http://consensus.nih.gov.
The conference was sponsored by the NIH Office of Medical Applications of Research and the National Institute on Aging, along with other NIH and Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 15-member panel included experts in the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, and family caregiving.
Source:
Lisa Ahramjian
NIH/National Institutes of Health, Office of Disease Prevention
"Alzheimer's disease is a feared and heart-breaking disease," said Dr. Martha L. Daviglus, conference panel chair and professor of preventive medicine and medicine at Northwestern University, Chicago. "We wish we could tell people that taking a pill or doing a puzzle every day would prevent this terrible disease, but current evidence doesn't support this."
The panel's assessment of the available evidence revealed that progress to understand how the onset of these conditions might be delayed or prevented is limited by inconsistent definitions of what constitutes Alzheimer's disease and cognitive decline. Other factors include incomplete understanding of the natural history of the disease and limited understanding of the aging process in general. The panel recommended that the research community and clinicians collaborate to develop, test, and uniformly adopt objective measures of baseline cognitive function and changes over time.
Although many non-modifiable risk factors have been examined, age is the strongest known risk factor for Alzheimer's disease. Additionally, a genetic variant of a cholesterol-ferrying protein (apolipoprotein E), has strong evidence of association with the risk for developing Alzheimer's disease. Although it is hoped that improved understanding of genetic risk factors may ultimately lead to effective therapies, currently these associations are primarily useful in the clinical research setting.
The panel determined that there is currently no evidence of even moderate scientific quality supporting the association of any modifiable factor - dietary supplement intake, use of prescription or non-prescription drugs, diet, exercise, and social engagement - with reduced risk of Alzheimer's disease. The evidence surrounding risk reduction for cognitive decline is similarly limited. Low-grade evidence shows weak associations between many lifestyle choices and reduced risk of Alzheimer's disease and cognitive decline.
Although there is little evidence that these interventions lessen cognitive decline, some are not necessarily harmful and may confer other benefits. However, the panel also emphasized the need for enhanced public understanding that these proposed prevention strategies are currently, at best, only loosely associated with improved outcomes. This means that carefully-designed randomized studies may reveal that these modifiable factors enhance, detract, or have no effect on preventing Alzheimer's disease and cognitive decline.
"These associations are examples of the classic chicken or the egg quandary. Are people able to stay mentally sharp over time because they are physically active and socially engaged or are they simply more likely to stay physically active and socially engaged because they are mentally sharp?" added Dr. Daviglus. "An association only tells us that these things are related, not that one causes the other."
The panel found that certain chronic diseases, such as diabetes and depression, and risk factors such as smoking are associated with increased risk of both Alzheimer's disease and cognitive decline. However, studies have not yet demonstrated that these medical or lifestyle factors actually cause or prevent Alzheimer's disease or cognitive decline, only that they are related.
There is insufficient evidence to support the use of pharmaceuticals or dietary supplements to prevent Alzheimer's disease or cognitive decline. Ongoing studies exploring factors including but not limited to physical activity, omega-3 fatty acids (typically found in fish), antihypertensive medications, and cognitive engagement may provide new insight into Alzheimer's disease and cognitive decline prevention.
The panel made a variety of recommendations to shape the future research agenda and fill identified gaps, while acknowledging that advancing our understanding of these complex conditions in order to develop conclusive, evidence-based prevention recommendations will require considerable time and resources. For example, the panel advocated launching long-term, longitudinal studies to better characterize the natural history and progression of these diseases in the community. They also recommended the establishment of registries for Alzheimer's disease and cognitive decline, modeled on existing registries for cancer.
Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. There are numerous ongoing or planned investigations which may offer promising new insights regarding the causes and prevention of these diseases.
An updated version of the panel's draft consensus statement, which incorporates comments received during the public session, are posted at http://consensus.nih.gov.
The conference was sponsored by the NIH Office of Medical Applications of Research and the National Institute on Aging, along with other NIH and Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 15-member panel included experts in the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, and family caregiving.
Source:
Lisa Ahramjian
NIH/National Institutes of Health, Office of Disease Prevention
Subscribe to:
Posts (Atom)