[Source: ScienceDaily] - A new suggests the reliability of the Alzheimer's Disease Assessment Scale – Cognitive (ADAS-Cog) may vary and possess the ability to affect clinical trial outcomes.
Moreover, this study further suggests that ADAS-Cog rater training and experience are factors that contribute to variances seen in this assessment tool.
The importance of a reliable diagnosis of the Alzheimer's disease (AD) is critical as new pharmacotherapies are being developed. The ADAS-cog is considered the gold-standard and the most popular cognitive testing instrument used in clinical trials to detect changes in the core symptoms of AD.
This study critically looks at various factors that might influence the way the ADAS-cog is administered and therefore may lead to and yield unintended outcomes. The study found factors such as rater training, rater education, variance in time allotment during testing as well as rater experience and individual judgment may contribute to variance in scoring when using this assessment.
"Clinical trials for the possible treatment of Alzheimer's disease and other dementias are becoming more expansive and being run in many countries. The necessity for the primary outcome instrument to be administered consistently in different countries, cultures and between different clinical trials is critical if we are to determine which treatment works better than others. Any variability in how the instruments are administered can adversely affect the ability to detect positive outcomes," says Donald Connor PhD, PhD, director of neuropsychology at Banner Health's Sun Health Research Institute.
Rater experiences were not the only factors that contributed to variances in ADAS-cog scoring. The study also suggested that test materials changed over time including large ranges in the quality of naming materials, word card decks, instruction manuals and worksheets, all factors that can affect outcomes.
"Even as we try to develop better instruments for the detection of meaningful change we must make sure that our current instruments are utilized as effectively as possible," Dr. Connor says. "As the population continues to age rapidly and new Alzheimer's medications are being developed, it is critical that all who are involved in clinical evaluation and testing does so with precision and consistency."
The study is published in the November issue of the Journal of Alzheimer's Disease (Volume 15:3).
Showing posts with label Alzheimer's Disease. Show all posts
Showing posts with label Alzheimer's Disease. Show all posts
Tuesday, November 25, 2008
Wednesday, October 29, 2008
Ultrasound Shown To Exert Remote Control Of Brain Circuits
[Source: ScienceDaily] - In a twist on nontraditional uses of ultrasound, a group of neuroscientists at Arizona State University has developed pulsed ultrasound techniques that can remotely stimulate brain circuit activity.
Their findings, published in the Oct. 29 issue of the journal Public Library of Science (PLoS) One, provide insights into how low-power ultrasound can be harnessed for the noninvasive neurostimulation of brain circuits and offers the potential for new treatments of brain disorders and disease.
While it might be hard to imagine the day where doctors could treat post traumatic stress disorders, traumatic brain injury and even Alzheimer's disease with the flip of a switch, most of us have in fact experienced some of ultrasound's numerous applications in our daily lives. For example, ultrasound has been used in fetal and other diagnostic medical imaging, ultrasonic teeth cleaning, physiotherapies, or surgical ablation. Ultrasound also provides a multitude of other non-medical uses, including pharmaceutical manufacturing, food processing, nondestructive materials testing, sonar, communications, oceanography and acoustic mapping.
"Studies of ultrasound and its interactions with biological tissues have a rich history dating back to the late 1920s," lead investigator William "Jamie" Tyler points out. "Several research groups have, for more than a half-century, demonstrated that ultrasound can produce changes in excitable tissues, such as nerve and/or muscle, but detailed studies in neurons at the cellular level have been lacking."
"We were able to unravel how ultrasound can stimulate the electrical activity of neurons by optically monitoring the activity of neuronal circuits, while we simultaneously propagated low-intensity, low-frequency ultrasound through brain tissues," says Tyler, assistant professor of neurobiology and bioimaging in the School of Life Sciences in the College of Liberal Arts and Sciences.
Led by Tyler, the ASU research group discovered that remotely delivered low intensity, low frequency ultrasound (LILFU) increased the activity of voltage-gated sodium and calcium channels in a manner sufficient to trigger action potentials and the release of neurotransmitter from synapses. Since these processes are fundamental to the transfer of information among neurons, the authors pose that this type of ultrasound provides a powerful new tool for modulating the activity of neural circuits.
"Many of the stimulation methods used by neuroscientists require the use and implantation of stimulating electrodes, requiring direct contact with nervous tissue or the introduction of exogenous proteins, such as those used for the light-activation of neurons," Tyler explains.
The search for new types of noninvasive neurostimulation methods led them to revisit ultrasound.
"We were quite surprised to find that ultrasound at power levels lower than those typically used in routine diagnostic medical imaging procedures could produce an increase in the activity of neurons while higher power levels produced very little effect on their activity," Tyler says.
Other neuroscientists and engineers have also been rapidly developing new neurostimulation methods for controlling nervous system activity and several approaches show promise for the treatment of a wide variety of nervous system disorders. For example, Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) have been shown to be effective in the management of psychiatric disorders such as depression, bipolar disorders, post-traumatic stress disorder, and drug addition, as well as for therapies of neurological diseases such as Parkinson's disease, Alzheimer's disease, Tourette Syndrome, epilepsy, dystonia, stuttering, tinnitus, recovery of cognitive and motor function following stroke, and chronic pain. Up until now, these two techniques have captured the attention of physicians and scientists; however, these therapies still pose risks to patients because they require the surgical implantation of stimulating electrodes. Thus, these types of therapies are often only available to patients presenting the worst of prognoses.
One prior stumbling block to using ultrasound noninvasively in the brain has been the skull. However, the acoustic frequencies utilized by Tyler and his colleagues to construct their pulsed ultrasound waveforms, overlap with a frequency range where optimal energy gains are achieved between transcranial transmission and brain absorption of ultrasound – which allows the ultrasound to penetrate bone and yet prevent damage to the soft tissues. Their findings are supported by other studies examining the potential of high-intensity focused ultrasound for ablating brain tissues, where it was shown that low-frequency ultrasound could be focused through human skulls.
When asked about the potential of using his groups' methods to remotely control brain activity, Tyler says: "One might be able to envision potential applications ranging from medical interventions to use in video gaming or the creation of artificial memories along the lines of Arnold Schwarzenegger's character in 'Total Recall.' Imagine taking a vacation without actually going anywhere?
"Obviously, we need to conduct further research and development, but one of the most exhilarating prospects is that low intensity, low frequency ultrasound permit deep-brain stimulation procedures without requiring exogenous proteins or surgically implanted medical devices," he adds.
Tyler and the other ASU researchers will now focus on further characterization of the influence of ultrasound on intact brain circuits and translational research, taking low intensity ultrasound from the lab into pre-clinical trials and treatment of neurological diseases.
Their findings, published in the Oct. 29 issue of the journal Public Library of Science (PLoS) One, provide insights into how low-power ultrasound can be harnessed for the noninvasive neurostimulation of brain circuits and offers the potential for new treatments of brain disorders and disease.
While it might be hard to imagine the day where doctors could treat post traumatic stress disorders, traumatic brain injury and even Alzheimer's disease with the flip of a switch, most of us have in fact experienced some of ultrasound's numerous applications in our daily lives. For example, ultrasound has been used in fetal and other diagnostic medical imaging, ultrasonic teeth cleaning, physiotherapies, or surgical ablation. Ultrasound also provides a multitude of other non-medical uses, including pharmaceutical manufacturing, food processing, nondestructive materials testing, sonar, communications, oceanography and acoustic mapping.
"Studies of ultrasound and its interactions with biological tissues have a rich history dating back to the late 1920s," lead investigator William "Jamie" Tyler points out. "Several research groups have, for more than a half-century, demonstrated that ultrasound can produce changes in excitable tissues, such as nerve and/or muscle, but detailed studies in neurons at the cellular level have been lacking."
"We were able to unravel how ultrasound can stimulate the electrical activity of neurons by optically monitoring the activity of neuronal circuits, while we simultaneously propagated low-intensity, low-frequency ultrasound through brain tissues," says Tyler, assistant professor of neurobiology and bioimaging in the School of Life Sciences in the College of Liberal Arts and Sciences.
Led by Tyler, the ASU research group discovered that remotely delivered low intensity, low frequency ultrasound (LILFU) increased the activity of voltage-gated sodium and calcium channels in a manner sufficient to trigger action potentials and the release of neurotransmitter from synapses. Since these processes are fundamental to the transfer of information among neurons, the authors pose that this type of ultrasound provides a powerful new tool for modulating the activity of neural circuits.
"Many of the stimulation methods used by neuroscientists require the use and implantation of stimulating electrodes, requiring direct contact with nervous tissue or the introduction of exogenous proteins, such as those used for the light-activation of neurons," Tyler explains.
The search for new types of noninvasive neurostimulation methods led them to revisit ultrasound.
"We were quite surprised to find that ultrasound at power levels lower than those typically used in routine diagnostic medical imaging procedures could produce an increase in the activity of neurons while higher power levels produced very little effect on their activity," Tyler says.
Other neuroscientists and engineers have also been rapidly developing new neurostimulation methods for controlling nervous system activity and several approaches show promise for the treatment of a wide variety of nervous system disorders. For example, Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) have been shown to be effective in the management of psychiatric disorders such as depression, bipolar disorders, post-traumatic stress disorder, and drug addition, as well as for therapies of neurological diseases such as Parkinson's disease, Alzheimer's disease, Tourette Syndrome, epilepsy, dystonia, stuttering, tinnitus, recovery of cognitive and motor function following stroke, and chronic pain. Up until now, these two techniques have captured the attention of physicians and scientists; however, these therapies still pose risks to patients because they require the surgical implantation of stimulating electrodes. Thus, these types of therapies are often only available to patients presenting the worst of prognoses.
One prior stumbling block to using ultrasound noninvasively in the brain has been the skull. However, the acoustic frequencies utilized by Tyler and his colleagues to construct their pulsed ultrasound waveforms, overlap with a frequency range where optimal energy gains are achieved between transcranial transmission and brain absorption of ultrasound – which allows the ultrasound to penetrate bone and yet prevent damage to the soft tissues. Their findings are supported by other studies examining the potential of high-intensity focused ultrasound for ablating brain tissues, where it was shown that low-frequency ultrasound could be focused through human skulls.
When asked about the potential of using his groups' methods to remotely control brain activity, Tyler says: "One might be able to envision potential applications ranging from medical interventions to use in video gaming or the creation of artificial memories along the lines of Arnold Schwarzenegger's character in 'Total Recall.' Imagine taking a vacation without actually going anywhere?
"Obviously, we need to conduct further research and development, but one of the most exhilarating prospects is that low intensity, low frequency ultrasound permit deep-brain stimulation procedures without requiring exogenous proteins or surgically implanted medical devices," he adds.
Tyler and the other ASU researchers will now focus on further characterization of the influence of ultrasound on intact brain circuits and translational research, taking low intensity ultrasound from the lab into pre-clinical trials and treatment of neurological diseases.
Monday, September 15, 2008
International TGen-led team finds link between brain protein and Alzheimer's disease
[Source: TGen] - Investigators at the Translational Genomics Research Institute (TGen) today announced a link between the brain protein KIBRA and Alzheimer's disease, a discovery that could lead to promising new treatments for this memory-robbing disorder.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
Friday, September 5, 2008
Banner researchers part of Alzheimer's study
[Source: East Valley Tribune, Mary K. Reinhart] - Arizona researchers are part of a nationwide study involving a new drug that could halt the progression of Alzheimer's disease by preventing plaque from forming in the brain.
Scientists at Banner Alzheimer's Institute in Phoenix and Banner's newly acquired Sun Health Research Institute in Sun City are looking for volunteers with mild to moderate dementia to take part in a 18-month clinical trial.
The experimental drug has the potential to stop plaque formation - one of the hallmarks of the brain-withering disease - by preventing the abnormal proteins from binding to a receptor in the brain.
Unlike the medications commonly used to treat Alzheimer's disease, the drug is designed to attack the cause rather than its symptoms.
"This is something that actually goes to the pathology of the disease," said Dr. Roy Yaari of the Banner Alzheimer's Institute and a principal local investigator.
Deposits of abnormal proteins, or plaque, can build up in the brains of Alzheimer's patients, causing nerve damage and inflammation that interfere with brain function and cause symptoms, like memory loss and behavior change, associated with dementia.
In patients with Alzheimer's, certain proteins, called amyloid beta, are abnormally cleaved and float freely between the brain and bloodstream, looking to attach to other proteins and form the sticky plaque buildup.
Scientists discovered that the experimental drug has the potential to stop plaque formation by preventing it from binding to a receptor in the brain known as RAGE. Typically, the receptor would allow the protein to move back and forth between the brain and the bloodstream.
"If you block the enzyme, once (the protein) leaves, it can't get back in," Yaari said. "What this drug does is it blocks it from coming back into the brain."
About 400 people nationwide are needed for the second phase of clinical trials, sponsored by Pfizer and the National Institute on Aging.
"There's been a lot of interest in this. These slots are going quickly," said Dr. Sandra Jacobson, a neuropsychiatrist with Sun Health and a co-investigator in the study.
Earlier studies on animals and humans found few side effects, other than some gastrointestinal discomfort, Jacobson said, which is common when a new drug is introduced.
"Everything that we know so far about this molecule makes us think this is safe," she said.
Study volunteers must be 50 years or older and free of any serious diseases within the past three months. They will be randomly assigned to one of three groups, with two groups receiving different doses of the medication and the third group a placebo. Participants will be monitored during at least 12 clinic visits, including MRIs, cognitive testing and electrocardiograms.
"In addition to monitoring disease progression through cognitive tests, we will examine various biological markers of the disease," Yaari said.
Much of the preliminary research connecting RAGE to the plaque was done by scientists at Columbia University, the University of Perugia in Italy and the University of Magdeburg in Germany.
The study, led by the Alzheimer's Disease Cooperative Study at the University of California, San Diego, is under way at 40 sites nationwide.
Scientists at Banner Alzheimer's Institute in Phoenix and Banner's newly acquired Sun Health Research Institute in Sun City are looking for volunteers with mild to moderate dementia to take part in a 18-month clinical trial.
The experimental drug has the potential to stop plaque formation - one of the hallmarks of the brain-withering disease - by preventing the abnormal proteins from binding to a receptor in the brain.
Unlike the medications commonly used to treat Alzheimer's disease, the drug is designed to attack the cause rather than its symptoms.
"This is something that actually goes to the pathology of the disease," said Dr. Roy Yaari of the Banner Alzheimer's Institute and a principal local investigator.
Deposits of abnormal proteins, or plaque, can build up in the brains of Alzheimer's patients, causing nerve damage and inflammation that interfere with brain function and cause symptoms, like memory loss and behavior change, associated with dementia.
In patients with Alzheimer's, certain proteins, called amyloid beta, are abnormally cleaved and float freely between the brain and bloodstream, looking to attach to other proteins and form the sticky plaque buildup.
Scientists discovered that the experimental drug has the potential to stop plaque formation by preventing it from binding to a receptor in the brain known as RAGE. Typically, the receptor would allow the protein to move back and forth between the brain and the bloodstream.
"If you block the enzyme, once (the protein) leaves, it can't get back in," Yaari said. "What this drug does is it blocks it from coming back into the brain."
About 400 people nationwide are needed for the second phase of clinical trials, sponsored by Pfizer and the National Institute on Aging.
"There's been a lot of interest in this. These slots are going quickly," said Dr. Sandra Jacobson, a neuropsychiatrist with Sun Health and a co-investigator in the study.
Earlier studies on animals and humans found few side effects, other than some gastrointestinal discomfort, Jacobson said, which is common when a new drug is introduced.
"Everything that we know so far about this molecule makes us think this is safe," she said.
Study volunteers must be 50 years or older and free of any serious diseases within the past three months. They will be randomly assigned to one of three groups, with two groups receiving different doses of the medication and the third group a placebo. Participants will be monitored during at least 12 clinic visits, including MRIs, cognitive testing and electrocardiograms.
"In addition to monitoring disease progression through cognitive tests, we will examine various biological markers of the disease," Yaari said.
Much of the preliminary research connecting RAGE to the plaque was done by scientists at Columbia University, the University of Perugia in Italy and the University of Magdeburg in Germany.
The study, led by the Alzheimer's Disease Cooperative Study at the University of California, San Diego, is under way at 40 sites nationwide.
Wednesday, September 3, 2008
Banner completes acquisition of Sun Health
[Source: Ken Alltucker , The Arizona Republic] - Banner Health this week completed its $316 million purchase of Sun Health Corp. and immediately swapped out the management teams and changed the names of Sun Health's two hospitals located in the Sun City area.
Long-time fixtures in the Sun City and Sun City West communities, the facilities are now named Banner Boswell Medical Center and Banner Del. E. Webb Medical Center.
Up to 40 duplicate executive and administrative positions have been eliminated as a result of the merger, and more positions may be impacted as hospital operations are converted over the coming months, Banner representatives said Tuesday. Non-executives whose jobs are eliminated will receive job-assistance service through Banner's career-transition center.
The deal bolsters Banner's position as Arizona's largest hospital group, creating a dominant 11-hospital organization with about 28,000 employees, 3,300 beds, and significant influence over the Valley's health-care system. Banner is the second-largest private employer in the Phoenix area, trailing only Wal-Mart.
"All of our planning efforts have been focused on this week for a long time," Banner CEO Peter Fine said. The Sun City communities "can expect Banner to continue to invest resources into their community to provide the best health-care service that we can and continue to support all the efforts they have had over time."
The Banner-Sun Health merger was announced nearly one year ago and received clearance from the Federal Trade Commission in late June, removing one potential regulatory hurdle to the combination of the two hospital groups.
In July, Banner issued about $1.3 billion in bonds to refinance debt, fund ongoing capital projects and pay for the $316 million purchase of Sun Health.
Terms of the merger required Banner to assume just over $200 million in Sun Health debt.
Three entities from the original Sun Health - Sun Health Foundation, Sun Health Auxiliary and Sun Health Properties - all will keep their name because they were not part of the merger.
Sun Health Research Institute (SHRI), which has drawn national acclaim for its research of age-related diseases such as Alzheimer's, will retain its name after the merger. But like the hospitals, its management was reshuffled.
SHRI CEO Joe Rogers agreed to step down and take a position as a staff scientist. Bill Camp was named CEO of Sun Health Research Institute and Marwan Sabbagh was named chief medical officer.
"I'm just going to be one of the scientists now," Rogers said Tuesday. "But I had a wonderful ride. I am looking forward to getting back in the lab and continue what I started 35 years ago: creating a cure," for Alzheimer's disease.
Banner representatives said that Sun Health's volunteers and community fundraising efforts will be pivotal to the hospital system's overall financial success. The Sun Health hospitals were heavily dependent on Medicare, which often reimburses at a lower rate than private insurers.
Other Sun Health entities that would be folded into Banner include Sun Health MediSun, Sun Health Boswell Rehabilitation Center, Sun Health Residence for Special Adults, Sun Health Olive Branch Senior Center and Sun Health Community Education & Wellness Center.
Meanwhile, Phoenix Children's Hospital is among the hospitals interested in the outcome of the Banner-Sun Health merger.
Last year, Phoenix Children's Hospital announced plans to open a pediatric urgent-care clinic with Sun Health at a planned medical campus in Surprise.
"That was moving along nicely before the merger, but it has since been on hold, appropriately so," said Robert Meyer, chief executive officer of Phoenix Children's Hospital. "We would obviously have an interest in continuing discussions."
Still, Banner is expanding its own children's hospital at Banner Desert Medical Center in Mesa, and has significantly ramped up its pediatric services. It's unclear if Banner would need to partner with Phoenix Children's Hospital in Surprise.
Fine said Banner has not yet made a decision whether to continue the Surprise development.
"There are other things that were in early stages of development - Surprise being an example of one - that we will take our time and review," he said.
Meyer said Phoenix Children's Hospital has continued its expansion in the West Valley, purchasing a building near 51st Avenue and Loop 101 with plans to open a pediatric urgent-care facility there by mid-2009.
Long-time fixtures in the Sun City and Sun City West communities, the facilities are now named Banner Boswell Medical Center and Banner Del. E. Webb Medical Center.
Up to 40 duplicate executive and administrative positions have been eliminated as a result of the merger, and more positions may be impacted as hospital operations are converted over the coming months, Banner representatives said Tuesday. Non-executives whose jobs are eliminated will receive job-assistance service through Banner's career-transition center.
The deal bolsters Banner's position as Arizona's largest hospital group, creating a dominant 11-hospital organization with about 28,000 employees, 3,300 beds, and significant influence over the Valley's health-care system. Banner is the second-largest private employer in the Phoenix area, trailing only Wal-Mart.
"All of our planning efforts have been focused on this week for a long time," Banner CEO Peter Fine said. The Sun City communities "can expect Banner to continue to invest resources into their community to provide the best health-care service that we can and continue to support all the efforts they have had over time."
The Banner-Sun Health merger was announced nearly one year ago and received clearance from the Federal Trade Commission in late June, removing one potential regulatory hurdle to the combination of the two hospital groups.
In July, Banner issued about $1.3 billion in bonds to refinance debt, fund ongoing capital projects and pay for the $316 million purchase of Sun Health.
Terms of the merger required Banner to assume just over $200 million in Sun Health debt.
Three entities from the original Sun Health - Sun Health Foundation, Sun Health Auxiliary and Sun Health Properties - all will keep their name because they were not part of the merger.
Sun Health Research Institute (SHRI), which has drawn national acclaim for its research of age-related diseases such as Alzheimer's, will retain its name after the merger. But like the hospitals, its management was reshuffled.
SHRI CEO Joe Rogers agreed to step down and take a position as a staff scientist. Bill Camp was named CEO of Sun Health Research Institute and Marwan Sabbagh was named chief medical officer.
"I'm just going to be one of the scientists now," Rogers said Tuesday. "But I had a wonderful ride. I am looking forward to getting back in the lab and continue what I started 35 years ago: creating a cure," for Alzheimer's disease.
Banner representatives said that Sun Health's volunteers and community fundraising efforts will be pivotal to the hospital system's overall financial success. The Sun Health hospitals were heavily dependent on Medicare, which often reimburses at a lower rate than private insurers.
Other Sun Health entities that would be folded into Banner include Sun Health MediSun, Sun Health Boswell Rehabilitation Center, Sun Health Residence for Special Adults, Sun Health Olive Branch Senior Center and Sun Health Community Education & Wellness Center.
Meanwhile, Phoenix Children's Hospital is among the hospitals interested in the outcome of the Banner-Sun Health merger.
Last year, Phoenix Children's Hospital announced plans to open a pediatric urgent-care clinic with Sun Health at a planned medical campus in Surprise.
"That was moving along nicely before the merger, but it has since been on hold, appropriately so," said Robert Meyer, chief executive officer of Phoenix Children's Hospital. "We would obviously have an interest in continuing discussions."
Still, Banner is expanding its own children's hospital at Banner Desert Medical Center in Mesa, and has significantly ramped up its pediatric services. It's unclear if Banner would need to partner with Phoenix Children's Hospital in Surprise.
Fine said Banner has not yet made a decision whether to continue the Surprise development.
"There are other things that were in early stages of development - Surprise being an example of one - that we will take our time and review," he said.
Meyer said Phoenix Children's Hospital has continued its expansion in the West Valley, purchasing a building near 51st Avenue and Loop 101 with plans to open a pediatric urgent-care facility there by mid-2009.
Tuesday, August 19, 2008
Power3 Medical Products, Inc. Provides Progress Report – NuroPro® Clinical Validation Study of Serum Biomarkers for Alzheimer’s Disease
[Source: BUSINESS WIRE] - Power3 Medical Products, Inc. (OTCBB:PWRM), a leading proteomics company specializing in the development and commercialization of diagnostic tests for early detection of breast cancer and neurodegenerative diseases, is providing an interim status report of its international validation study of the company’s NuroPro® blood serum biomarker test for Alzheimer’s disease.
Power3 is currently conducting a 300-patient clinical validation study of its NuroPro® blood serum test for Alzheimer’s and Parkinson’s disease in collaboration with Dr. Marwan Sabbagh, the Director of Clinical Research at the Cleo Roberts Center of Clinical Research at the Sun Health Research Institute in Sun City, Arizona. “The preliminary results of the Power3’s study look very promising. Clinicians around the world look forward to adding a tool to diagnose and treat Alzheimer’s earlier and therefore give the best care to their patients,” says Dr. Sabbagh. To date, 92 Alzheimer and Control patient samples have been analyzed in Power3’s CLIA certified laboratory and have demonstrated high sensitivity and specificity in the diagnosis of Alzheimer’s disease.
“This study confirms Power3’s panel of Neurodegenerative biomarkers’ ability to diagnose Alzheimer’s disease with superior sensitivity and specificity with results in the 95% range. Additionally, the current study validates Power3’s collection, storage, shipping, processing, and biostatistical analysis methods,” says Dr. Essam Sheta, the Director of Power3’s CLIA laboratory. Power3 expects to conclude the initial Alzheimer’s validation study in September 2008 and publish the validation study results soon after.
“Power3 is planning to expand its validation study for NuroPro® to include two additional clinical sites within the U.S. Larger patient cohorts of different ethnic and environmental backgrounds will strengthen the validity of NuroPro’s® applicability in the diagnosis of neurodegenerative diseases,” Steven B. Rash, Chief Executive Officer, commented. Mr. Rash added “This study confirms that Power3 is rapidly approaching the stage to commercializing the first ever blood serum proteomic tests for the diagnosis of neurodegenerative diseases. These encouraging Alzheimer’s test results, and the numerous validation studies that are currently underway for Parkinson’s disease, ALS, and similar neurological disorders, demonstrates our commitment to bringing these tests to market in late 2008 or early 2009. We believe this test will be a major breakthrough for patients and physicians, as it will offer a means to detect neurodegenerative diseases at their earliest stages, allowing physicians to begin treatment at stages which will produce more positive outcomes.”
In addition to the Alzheimer’s clinical validation study being conducted in collaboration with Dr. Sabbagh, the Company continues its ongoing Parkinson’s validation study under the direction of the principal investigator, Dr. Katerina Markopoulou at the Research Institute at the University of Thessaly, Greece. Power3 expects to conclude this Parkinson’s validation study in September and will publish the results soon after.
Power3 is currently conducting a 300-patient clinical validation study of its NuroPro® blood serum test for Alzheimer’s and Parkinson’s disease in collaboration with Dr. Marwan Sabbagh, the Director of Clinical Research at the Cleo Roberts Center of Clinical Research at the Sun Health Research Institute in Sun City, Arizona. “The preliminary results of the Power3’s study look very promising. Clinicians around the world look forward to adding a tool to diagnose and treat Alzheimer’s earlier and therefore give the best care to their patients,” says Dr. Sabbagh. To date, 92 Alzheimer and Control patient samples have been analyzed in Power3’s CLIA certified laboratory and have demonstrated high sensitivity and specificity in the diagnosis of Alzheimer’s disease.
“This study confirms Power3’s panel of Neurodegenerative biomarkers’ ability to diagnose Alzheimer’s disease with superior sensitivity and specificity with results in the 95% range. Additionally, the current study validates Power3’s collection, storage, shipping, processing, and biostatistical analysis methods,” says Dr. Essam Sheta, the Director of Power3’s CLIA laboratory. Power3 expects to conclude the initial Alzheimer’s validation study in September 2008 and publish the validation study results soon after.
“Power3 is planning to expand its validation study for NuroPro® to include two additional clinical sites within the U.S. Larger patient cohorts of different ethnic and environmental backgrounds will strengthen the validity of NuroPro’s® applicability in the diagnosis of neurodegenerative diseases,” Steven B. Rash, Chief Executive Officer, commented. Mr. Rash added “This study confirms that Power3 is rapidly approaching the stage to commercializing the first ever blood serum proteomic tests for the diagnosis of neurodegenerative diseases. These encouraging Alzheimer’s test results, and the numerous validation studies that are currently underway for Parkinson’s disease, ALS, and similar neurological disorders, demonstrates our commitment to bringing these tests to market in late 2008 or early 2009. We believe this test will be a major breakthrough for patients and physicians, as it will offer a means to detect neurodegenerative diseases at their earliest stages, allowing physicians to begin treatment at stages which will produce more positive outcomes.”
In addition to the Alzheimer’s clinical validation study being conducted in collaboration with Dr. Sabbagh, the Company continues its ongoing Parkinson’s validation study under the direction of the principal investigator, Dr. Katerina Markopoulou at the Research Institute at the University of Thessaly, Greece. Power3 expects to conclude this Parkinson’s validation study in September and will publish the results soon after.
Monday, August 4, 2008
Markers in Blood and Spinal Fluid, and a New Imaging Agent, Show Promise for Early Detection of Alzheimer's
[Source: PRNewswire] - With the continued aging of the population and the growing epidemic of Alzheimer's, early detection of the disease is crucial for risk assessment, testing new therapies, and eventual early intervention with better drugs, once they are developed. Four studies reported today at the Alzheimer's Association's 2008 International Conference on Alzheimer's Disease (ICAD 2008) in Chicago bring us closer to that goal of early detection by describing advances in biomarkers.
A biomarker is a substance or characteristic that can be objectively measured and evaluated as an indicator of normal body processes, disease processes, or the body's response(s) to a therapeutic intervention.
It is widely believed that Alzheimer's disease brain changes, including amyloid plaques and neurofibrillary tangles, begin many years before symptoms are evident or there is significant death of brain cells. It is critical to identify affected individuals while they are still cognitively normal so that future disease modifying therapies can preserve normal function. The testing and eventual use of such therapies requires identification of affected and "at risk" individuals in order to steer them to clinical trials, and to direct and monitor therapy.
"Discovery of measurable markers that track with the presence of Alzheimer's pathology and that predict the development of cognitive decline in people who are still cognitively normal, known as 'antecedent biomarkers,' are especially needed," said William Thies, PhD, vice president of Medical and Scientific Relations at the Alzheimer's Association. "It is greatly preferable that these markers be easy to obtain, such as in samples of blood or urine, or through readily available imaging technologies, such as MRI and PET."
Blood Test on White Blood Cells May Be Useful for Early Detection of Alzheimer's
Healthy brain cells do not go through the process of division and replication (known as the "cell cycle") that is common in other cells in the body. However, in Alzheimer's disease, brain cells have demonstrated an abnormal tendency to prepare to re-enter this cell cycle, which may increase their likelihood of dying or directly cause their death.
The equivalent cell cycle defect is found in lymphocytes of people with Alzheimer's. Lymphocytes are white blood cells in the immune system that can easily be collected for testing by a simple blood draw. Professor Thomas Arendt, Director of the Paul Flechsig Institute, University of Leipzig, Germany, thought that this suggested a vehicle for detecting Alzheimer's.
In a study performed in the U.S. by GW Medical, the licensor of Arendt's technology, Arendt and colleagues measured the expression of CD-69 (a protein involved in white blood cell growth and production) on multiple cell lines in people with probable Alzheimer's (n=32), healthy controls (n=30) and other dementias, chiefly Parkinson's disease dementia, (n=26).
Variations in levels of CD-69 enabled the researcher to clearly differentiate between Alzheimer's subjects and demented Parkinson's subjects. It was accurate 91 percent of the time when the diagnosis was Alzheimer's and 92 percent of the time when it was Parkinson's dementia. The assay correctly differentiated people with Alzheimer's from cognitively normal subjects 88 percent of the time when the diagnosis was Alzheimer's and 82 percent of the time when the person was cognitively normal.
In addition, Arendt found that the test results did not vary with dementia severity as measured by the Mini Mental State Exam.
"The lack of variation suggests that this test may be useful in the early stages of Alzheimer's," Arendt said. "A larger trial is underway with results expected by late summer 2008. If confirmed, it will give primary care physicians a better, more accurate and non-invasive test for Alzheimer's disease."
Spinal Fluid Marker Tracks Brain Amyloid, May Identify Alzheimer's Before Symptoms
Some researchers believe that flaws in processes governing production, accumulation, or disposal of amyloid protein in the brain are the primary cause of Alzheimer's. AB42 is a particularly "sticky" variety of amyloid protein fragment that is more likely to aggregate into small clusters and eventually into the plaques that are considered one hallmark of the Alzheimer brain.
Anne M. Fagan, PhD, of the Washington University School of Medicine, St. Louis, MO, and colleagues previously demonstrated in a small group (n=24) that a low level of AB42 in cerebrospinal fluid (CSF) is an effective marker for determining the presence of amyloid in the brain as assessed by PET scans using a marker called Pittsburgh Compound B (PIB).
In a new study presented at ICAD 2008, Fagan reported on a much larger cohort (n=132; age 45-88 years, mean 65.7). This group included individuals who were non-demented plus those with very mild or mild dementia. Consistent with the prior study, the researchers observed a striking inverse relation between presence of amyloid in the brain and levels of AB42 in CSF.
Overall, those people with high amounts of brain amyloid (as indicated by PET scan images showing positive PIB-binding) had low CSF AB42 (36/37, 97%). Those with low levels of brain amyloid (negative PIB-binding) had high CSF AB42 (80/95, 84%). This was true regardless of cognitive status, indicating excellent sensitivity of CSF AB42 for identifying the presence of brain amyloid, according to the researchers.
In addition, they observed that three non-demented, low CSF AB42, PIB-positive study participants have subsequently received an Alzheimer's diagnosis suggesting that positive PIB and low CSF AB42 may be useful as markers of "preclinical Alzheimer's" (that is, Alzheimer's prior to visible symptoms).
"We found that CSF AB42 is an excellent marker for identifying the presence of amyloid in the brain, regardless of the person's cognitive status," Fagan said. "Our analyses also suggest that a decline in CSF AB42 may effectively identify non-demented individuals who are in the preclinical stage of Alzheimer's, even before they are PIB positive."
Brain Enzyme May Improve Alzheimer's Risk Assessment and Early Detection
Researchers have previously found elevated B-secretase (BACE1) activity in the brains of patients with Alzheimer's compared to healthy individuals. BACE1 is one of two enzymes involved in the pathological processing of amyloid precursor protein (APP) and the production of toxic AB (beta amyloid, the main constituent of amyloid plaques in the brains of people with Alzheimer's).
Professor Harald Hampel, of Trinity College Dublin, Ireland and the University of Munich, Germany, Professor Yong Shen, of Sun Health Research Institute, USA, and colleagues investigated whether BACE1 assessed in cerebrospinal fluid (CSF) may be a feasible biomarker candidate for predicting Alzheimer's in people with mild cognitive impairment (MCI). MCI is a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer's.
The research had two parts. In the first part, the scientists measured BACE1 levels in CSF in 80 people with Alzheimer's, 59 people with MCI, and 69 healthy elderly controls (HC) at two independent, international research centers. MCI subjects showed highly increased levels of BACE1 activity when compared to HC and people with Alzheimer's. BACE1 activity was significantly correlated with AB level. A subsequent validation study replicated these initial findings in a new and independent set of 41 people with Alzheimer's, 46 with amnestic MCI and elderly HC.
In the second part, 47 MCI subjects were clinically followed up over two years to assess the predictive value of BACE1 in combination with other biomarker candidates for predicting the conversion from MCI to Alzheimer's. The additional candidates were abnormal brain proteins total tau and phosphorylated tau measured in CSF, and baseline performance on a large neuropsychological testing battery. Fifteen (15) MCI subjects converted to Alzheimer's after a mean follow-up interval of 2.3 years. Analysis showed that BACE1 protein levels and ApoE genotype (a genetic risk factor for Alzheimer's) were the strongest predictors of conversion to Alzheimer's, after controlling for age and gender. The classification accuracy was 78%, the sensitivity was 80%, and the specificity was 77% for the combined model.
"These important findings pave the way for further rigorous assessment of BACE1 as an effective and accurate clinical diagnostic tool, which could significantly improve risk assessment and early detection of Alzheimer's," Hampel said. "We believe that BACE1 will be an excellent outcome biomarker to look at in ongoing clinical trials of anti-amyloid, disease modifying therapies. Furthermore, we are working on a blood-based diagnostic test for BACE1 as well."
Improved Amyloid Imaging Agents for PET in Development
A major recent advance in Alzheimer's is the ability to create images of amyloid in the brains of living people using positron emission tomography (PET) scanners. With PET, a radioactive compound, or tracer, is injected into the person to be scanned. The tracer attaches to a target substance in the body, in this case amyloid, which then "lights up" on the image captured by the scanner.
In research reported at ICAD 2008, Michael J. Pontecorvo, PhD, of Avid Radiopharmaceuticals, Philadelphia, PA, and colleagues reported the development of a novel 18F-labeled PET amyloid imaging agent, 18F-AV-45, that may eventually provide a practical approach for routine brain imaging for Alzheimer's
PET scanners are relatively common - they are available in most hospitals - yet one of the challenges to more widespread use of PET imaging in Alzheimer's is that the radioactivity of the first amyloid-imaging tracer, called 11C-PIB or Pittsburgh Compound B, is relatively short-lived. With this agent, based on radioactive carbon, half of the radioactivity is lost every 20 minutes. This means that it must be manufactured onsite, a process that requires a cyclotron (a type of particle accelerator), which is rarely found in community hospitals. This limitation has prompted a search for longer-lived tracers, such as 18F-labeled agents, based on radioactive fluorine, which would be suitable for regional production and wider community use.
In the study, three 18F-labeled compounds were evaluated in 42 cognitively healthy elderly volunteers and 39 individuals with Alzheimer's. Each participant received a single intravenous injection of one of the compounds followed by PET imaging.
People with Alzheimer's showed retention of all three tracers in brain areas expected to be high in amyloid. In contrast, cognitively healthy volunteers showed rapid removal of the tracers, with minimal retention in the brain. Two individuals diagnosed with Alzheimer's had a pattern of tracer uptake similar to healthy volunteers. Chart notes for both suggested unusual presentations - prominent Parkinsonism in one case and slowly progressive dementia in the other.
While the three compounds were similar in pattern and amount of tracer retention, they differed in how they were processed by the body in ways that favored one compound, 18F-AV-45. For example, 18F-AV-45 showed rapid uptake and steady levels were maintained in the brain between 50 and 90 minutes post injection. This allowed high quality images to be obtained from PET imaging beginning 50 minutes after 18F-AV-45 administration, with minimal inconvenience or delay for the patient or the imaging center, according to the researchers.
"18F-AV-45 is being used as a research tool today, but it has the potential to aid in the diagnosis and early detection of Alzheimer's in a community setting and may be a useful biomarker for the development and monitoring of novel amyloid reducing therapies," Pontecorvo said. "On the basis of the findings we reported today, Phase II trials with 18F-AV-45 have been initiated."
A biomarker is a substance or characteristic that can be objectively measured and evaluated as an indicator of normal body processes, disease processes, or the body's response(s) to a therapeutic intervention.
It is widely believed that Alzheimer's disease brain changes, including amyloid plaques and neurofibrillary tangles, begin many years before symptoms are evident or there is significant death of brain cells. It is critical to identify affected individuals while they are still cognitively normal so that future disease modifying therapies can preserve normal function. The testing and eventual use of such therapies requires identification of affected and "at risk" individuals in order to steer them to clinical trials, and to direct and monitor therapy.
"Discovery of measurable markers that track with the presence of Alzheimer's pathology and that predict the development of cognitive decline in people who are still cognitively normal, known as 'antecedent biomarkers,' are especially needed," said William Thies, PhD, vice president of Medical and Scientific Relations at the Alzheimer's Association. "It is greatly preferable that these markers be easy to obtain, such as in samples of blood or urine, or through readily available imaging technologies, such as MRI and PET."
Blood Test on White Blood Cells May Be Useful for Early Detection of Alzheimer's
Healthy brain cells do not go through the process of division and replication (known as the "cell cycle") that is common in other cells in the body. However, in Alzheimer's disease, brain cells have demonstrated an abnormal tendency to prepare to re-enter this cell cycle, which may increase their likelihood of dying or directly cause their death.
The equivalent cell cycle defect is found in lymphocytes of people with Alzheimer's. Lymphocytes are white blood cells in the immune system that can easily be collected for testing by a simple blood draw. Professor Thomas Arendt, Director of the Paul Flechsig Institute, University of Leipzig, Germany, thought that this suggested a vehicle for detecting Alzheimer's.
In a study performed in the U.S. by GW Medical, the licensor of Arendt's technology, Arendt and colleagues measured the expression of CD-69 (a protein involved in white blood cell growth and production) on multiple cell lines in people with probable Alzheimer's (n=32), healthy controls (n=30) and other dementias, chiefly Parkinson's disease dementia, (n=26).
Variations in levels of CD-69 enabled the researcher to clearly differentiate between Alzheimer's subjects and demented Parkinson's subjects. It was accurate 91 percent of the time when the diagnosis was Alzheimer's and 92 percent of the time when it was Parkinson's dementia. The assay correctly differentiated people with Alzheimer's from cognitively normal subjects 88 percent of the time when the diagnosis was Alzheimer's and 82 percent of the time when the person was cognitively normal.
In addition, Arendt found that the test results did not vary with dementia severity as measured by the Mini Mental State Exam.
"The lack of variation suggests that this test may be useful in the early stages of Alzheimer's," Arendt said. "A larger trial is underway with results expected by late summer 2008. If confirmed, it will give primary care physicians a better, more accurate and non-invasive test for Alzheimer's disease."
Spinal Fluid Marker Tracks Brain Amyloid, May Identify Alzheimer's Before Symptoms
Some researchers believe that flaws in processes governing production, accumulation, or disposal of amyloid protein in the brain are the primary cause of Alzheimer's. AB42 is a particularly "sticky" variety of amyloid protein fragment that is more likely to aggregate into small clusters and eventually into the plaques that are considered one hallmark of the Alzheimer brain.
Anne M. Fagan, PhD, of the Washington University School of Medicine, St. Louis, MO, and colleagues previously demonstrated in a small group (n=24) that a low level of AB42 in cerebrospinal fluid (CSF) is an effective marker for determining the presence of amyloid in the brain as assessed by PET scans using a marker called Pittsburgh Compound B (PIB).
In a new study presented at ICAD 2008, Fagan reported on a much larger cohort (n=132; age 45-88 years, mean 65.7). This group included individuals who were non-demented plus those with very mild or mild dementia. Consistent with the prior study, the researchers observed a striking inverse relation between presence of amyloid in the brain and levels of AB42 in CSF.
Overall, those people with high amounts of brain amyloid (as indicated by PET scan images showing positive PIB-binding) had low CSF AB42 (36/37, 97%). Those with low levels of brain amyloid (negative PIB-binding) had high CSF AB42 (80/95, 84%). This was true regardless of cognitive status, indicating excellent sensitivity of CSF AB42 for identifying the presence of brain amyloid, according to the researchers.
In addition, they observed that three non-demented, low CSF AB42, PIB-positive study participants have subsequently received an Alzheimer's diagnosis suggesting that positive PIB and low CSF AB42 may be useful as markers of "preclinical Alzheimer's" (that is, Alzheimer's prior to visible symptoms).
"We found that CSF AB42 is an excellent marker for identifying the presence of amyloid in the brain, regardless of the person's cognitive status," Fagan said. "Our analyses also suggest that a decline in CSF AB42 may effectively identify non-demented individuals who are in the preclinical stage of Alzheimer's, even before they are PIB positive."
Brain Enzyme May Improve Alzheimer's Risk Assessment and Early Detection
Researchers have previously found elevated B-secretase (BACE1) activity in the brains of patients with Alzheimer's compared to healthy individuals. BACE1 is one of two enzymes involved in the pathological processing of amyloid precursor protein (APP) and the production of toxic AB (beta amyloid, the main constituent of amyloid plaques in the brains of people with Alzheimer's).
Professor Harald Hampel, of Trinity College Dublin, Ireland and the University of Munich, Germany, Professor Yong Shen, of Sun Health Research Institute, USA, and colleagues investigated whether BACE1 assessed in cerebrospinal fluid (CSF) may be a feasible biomarker candidate for predicting Alzheimer's in people with mild cognitive impairment (MCI). MCI is a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer's.
The research had two parts. In the first part, the scientists measured BACE1 levels in CSF in 80 people with Alzheimer's, 59 people with MCI, and 69 healthy elderly controls (HC) at two independent, international research centers. MCI subjects showed highly increased levels of BACE1 activity when compared to HC and people with Alzheimer's. BACE1 activity was significantly correlated with AB level. A subsequent validation study replicated these initial findings in a new and independent set of 41 people with Alzheimer's, 46 with amnestic MCI and elderly HC.
In the second part, 47 MCI subjects were clinically followed up over two years to assess the predictive value of BACE1 in combination with other biomarker candidates for predicting the conversion from MCI to Alzheimer's. The additional candidates were abnormal brain proteins total tau and phosphorylated tau measured in CSF, and baseline performance on a large neuropsychological testing battery. Fifteen (15) MCI subjects converted to Alzheimer's after a mean follow-up interval of 2.3 years. Analysis showed that BACE1 protein levels and ApoE genotype (a genetic risk factor for Alzheimer's) were the strongest predictors of conversion to Alzheimer's, after controlling for age and gender. The classification accuracy was 78%, the sensitivity was 80%, and the specificity was 77% for the combined model.
"These important findings pave the way for further rigorous assessment of BACE1 as an effective and accurate clinical diagnostic tool, which could significantly improve risk assessment and early detection of Alzheimer's," Hampel said. "We believe that BACE1 will be an excellent outcome biomarker to look at in ongoing clinical trials of anti-amyloid, disease modifying therapies. Furthermore, we are working on a blood-based diagnostic test for BACE1 as well."
Improved Amyloid Imaging Agents for PET in Development
A major recent advance in Alzheimer's is the ability to create images of amyloid in the brains of living people using positron emission tomography (PET) scanners. With PET, a radioactive compound, or tracer, is injected into the person to be scanned. The tracer attaches to a target substance in the body, in this case amyloid, which then "lights up" on the image captured by the scanner.
In research reported at ICAD 2008, Michael J. Pontecorvo, PhD, of Avid Radiopharmaceuticals, Philadelphia, PA, and colleagues reported the development of a novel 18F-labeled PET amyloid imaging agent, 18F-AV-45, that may eventually provide a practical approach for routine brain imaging for Alzheimer's
PET scanners are relatively common - they are available in most hospitals - yet one of the challenges to more widespread use of PET imaging in Alzheimer's is that the radioactivity of the first amyloid-imaging tracer, called 11C-PIB or Pittsburgh Compound B, is relatively short-lived. With this agent, based on radioactive carbon, half of the radioactivity is lost every 20 minutes. This means that it must be manufactured onsite, a process that requires a cyclotron (a type of particle accelerator), which is rarely found in community hospitals. This limitation has prompted a search for longer-lived tracers, such as 18F-labeled agents, based on radioactive fluorine, which would be suitable for regional production and wider community use.
In the study, three 18F-labeled compounds were evaluated in 42 cognitively healthy elderly volunteers and 39 individuals with Alzheimer's. Each participant received a single intravenous injection of one of the compounds followed by PET imaging.
People with Alzheimer's showed retention of all three tracers in brain areas expected to be high in amyloid. In contrast, cognitively healthy volunteers showed rapid removal of the tracers, with minimal retention in the brain. Two individuals diagnosed with Alzheimer's had a pattern of tracer uptake similar to healthy volunteers. Chart notes for both suggested unusual presentations - prominent Parkinsonism in one case and slowly progressive dementia in the other.
While the three compounds were similar in pattern and amount of tracer retention, they differed in how they were processed by the body in ways that favored one compound, 18F-AV-45. For example, 18F-AV-45 showed rapid uptake and steady levels were maintained in the brain between 50 and 90 minutes post injection. This allowed high quality images to be obtained from PET imaging beginning 50 minutes after 18F-AV-45 administration, with minimal inconvenience or delay for the patient or the imaging center, according to the researchers.
"18F-AV-45 is being used as a research tool today, but it has the potential to aid in the diagnosis and early detection of Alzheimer's in a community setting and may be a useful biomarker for the development and monitoring of novel amyloid reducing therapies," Pontecorvo said. "On the basis of the findings we reported today, Phase II trials with 18F-AV-45 have been initiated."
Monday, July 28, 2008
Early-diagnosis blood tests for Alzheimer's disease in development
[Source: Shari Roan, Los Angeles Times Staff Writer] - People with Alzheimer's face an awkward juncture in the near future. They'll be able to learn early on whether they have Alzheimer's disease -- even if they can't do much about it.
With therapies to halt or slow the progression of Alzheimer's disease seeming ever more elusive, several blood tests currently in development could determine who has the disease even before symptoms develop or become severe. Researchers say they believe people would use such a test, if only to prepare for a future with the limitations wrought by dementia."It would be a boon to the field," says Dr. Ronald C. Petersen, a neurologist at the Mayo Clinic in Rochester, Minn. "Many, many people are at risk due to family history, age, genetic characteristics. But we don't have a good prediction formula for who will actually get the disease."
Alzheimer's disease is extremely difficult to diagnose in its early stages because the symptoms, such as memory problems, can also be attributed to normal aging or a number of other illnesses. Even the appearance of plaque in the brain is not considered a telltale sign of the disease because some older people have plaque but do not suffer from dementia. Doctors and patients need a test that is convenient, accurate, reliable and inexpensive, says Dr. Harold Varmus, the former director of the National Institutes of Health and a member of the Alzheimer’s Study Group(ASG), an independent working group mandated by Congress to develop a national strategic plan for Alzheimer's disease.
"It's clear that finding this disease at the earliest possible stage provides the best possible window for therapeutics," Varmus says. "If you can make an early diagnosis, you can think about trying to arrest the disease, which is better than trying to reverse it."
Targeted at research
A Redwood City, Calif., company, Satoris Inc., has announced plans to release a blood test for use in research later this year. A study published in the journal Nature Medicine in November examined blood samples from 259 people who had early- to late-stage Alzheimer's disease or did not have the disease. It found 18 proteins in the blood of Alzheimer's patients with concentrations different from normal individuals. The protein panel allowed for nearly 90% accuracy in diagnosing and characterizing the disease even among people with only a mild version of the disease called mild cognitive impairment.
The as-yet-unnamed test would be used initially with other diagnostic tests, such as brain scans, to provide a highly reliable result, says Cris McReynolds, president of Satoris. "It will be an important piece of information used with other information to make an accurate diagnosis."
McReynolds says he hopes a test for the general public will become available one or two years after researchers begin their work with it.
Another test, called NuroPro, is under development by Power3 Medical Products in the Woodlands, Texas. It measures 59 protein markers in the blood that distinguish people with Alzheimer's disease from those with Parkinson's disease as well as those without either disease. Data from a study by Sun Health Research Institute in Sun City, Ariz., are expected at the end of August, says Steven Rash, chief executive of Power3. He says the company hopes to launch a test for the public late this year.
It's too soon to tell if these tests are accurate enough to be diagnostic tests or if they may just suggest a higher risk for the disease, Petersen says.
Diagnostic tests that appear reliable in academic research settings may not be as impressive in the general population where "you take all comers," says Dr. P. Murali Doraiswamy, chief of biological psychiatry at Duke University and co-author of the new book "The Alzheimer's Action Plan."
"We should be cautious in applying this technology," he says. "I think people have a right to know, but at the same time people should be counseled fully and not be led into getting these tests without knowing the risks and benefits."
Test may lead to drug
The real value for a diagnostic blood test, at least initially, may be in research. Scientists are also optimistic that an early-diagnosis blood test will spark better drug trials and, ultimately, a blockbuster medication.
Many researchers believe that previous Alzheimer's drug trials have been hindered by inaccurate methods to identify subjects -- people who have the disease rather than some other type of dementia -- and by inferior tools to gauge a drug's effectiveness, such as through cognitive testing or asking people or their family members if the symptoms have improved.
Says McReynolds: "They have been operating in the dark."
With therapies to halt or slow the progression of Alzheimer's disease seeming ever more elusive, several blood tests currently in development could determine who has the disease even before symptoms develop or become severe. Researchers say they believe people would use such a test, if only to prepare for a future with the limitations wrought by dementia."It would be a boon to the field," says Dr. Ronald C. Petersen, a neurologist at the Mayo Clinic in Rochester, Minn. "Many, many people are at risk due to family history, age, genetic characteristics. But we don't have a good prediction formula for who will actually get the disease."
Alzheimer's disease is extremely difficult to diagnose in its early stages because the symptoms, such as memory problems, can also be attributed to normal aging or a number of other illnesses. Even the appearance of plaque in the brain is not considered a telltale sign of the disease because some older people have plaque but do not suffer from dementia. Doctors and patients need a test that is convenient, accurate, reliable and inexpensive, says Dr. Harold Varmus, the former director of the National Institutes of Health and a member of the Alzheimer’s Study Group(ASG), an independent working group mandated by Congress to develop a national strategic plan for Alzheimer's disease.
"It's clear that finding this disease at the earliest possible stage provides the best possible window for therapeutics," Varmus says. "If you can make an early diagnosis, you can think about trying to arrest the disease, which is better than trying to reverse it."
Targeted at research
A Redwood City, Calif., company, Satoris Inc., has announced plans to release a blood test for use in research later this year. A study published in the journal Nature Medicine in November examined blood samples from 259 people who had early- to late-stage Alzheimer's disease or did not have the disease. It found 18 proteins in the blood of Alzheimer's patients with concentrations different from normal individuals. The protein panel allowed for nearly 90% accuracy in diagnosing and characterizing the disease even among people with only a mild version of the disease called mild cognitive impairment.
The as-yet-unnamed test would be used initially with other diagnostic tests, such as brain scans, to provide a highly reliable result, says Cris McReynolds, president of Satoris. "It will be an important piece of information used with other information to make an accurate diagnosis."
McReynolds says he hopes a test for the general public will become available one or two years after researchers begin their work with it.
Another test, called NuroPro, is under development by Power3 Medical Products in the Woodlands, Texas. It measures 59 protein markers in the blood that distinguish people with Alzheimer's disease from those with Parkinson's disease as well as those without either disease. Data from a study by Sun Health Research Institute in Sun City, Ariz., are expected at the end of August, says Steven Rash, chief executive of Power3. He says the company hopes to launch a test for the public late this year.
It's too soon to tell if these tests are accurate enough to be diagnostic tests or if they may just suggest a higher risk for the disease, Petersen says.
Diagnostic tests that appear reliable in academic research settings may not be as impressive in the general population where "you take all comers," says Dr. P. Murali Doraiswamy, chief of biological psychiatry at Duke University and co-author of the new book "The Alzheimer's Action Plan."
"We should be cautious in applying this technology," he says. "I think people have a right to know, but at the same time people should be counseled fully and not be led into getting these tests without knowing the risks and benefits."
Test may lead to drug
The real value for a diagnostic blood test, at least initially, may be in research. Scientists are also optimistic that an early-diagnosis blood test will spark better drug trials and, ultimately, a blockbuster medication.
Many researchers believe that previous Alzheimer's drug trials have been hindered by inaccurate methods to identify subjects -- people who have the disease rather than some other type of dementia -- and by inferior tools to gauge a drug's effectiveness, such as through cognitive testing or asking people or their family members if the symptoms have improved.
Says McReynolds: "They have been operating in the dark."
Monday, July 14, 2008
UA researcher probes potential for plants' power in medicine
[Source: Tom Beal, ARIZONA DAILY STAR] - David Gang's laboratory and the kitchen he shares with his wife and six children contain some of the same ingredients.
At the University of Arizona, where he is a professor in the Department of Plant Sciences, Gang grows turmeric and ginger plants in greenhouses on the roof of a parking garage on East Sixth Street.
He raises basil plants in controlled chambers in the basement of the Bio5 Research Institute across campus.
At home, Gang sprinkles turmeric on just about everything he cooks, even adds it to fruit smoothies.
Turmeric, a staple of Indian cooking that gives curries their bright yellow color, doesn't flavor things all that much, he said. "The kids don't even notice it," he said.
Ginger and basil also figure in their diet. They taste good, Gang said, and they are good for you.
He knows ginger works. He's been chewing it for years since discovering that it eased an undiagnosable stomach ailment he developed during his graduate school years.
"It had a dramatic effect," he said. "I went from being sick every day to being well most of the time."
Gang said his recovery is part of the reason he decided to concentrate his research on learning how plants make the remarkable substances that modern scientists are just beginning to study for their healthful effects.
Knowledge of the properties is not new, Gang said. "Ayurvedic practitioners in India have known about them for thousands of years."
Gang and his group are trying to identify and uncover the distinct compounds that make them work.
Turmeric is hot in natural healing circles, having been reidentified in recent years as a potent anti-inflammatory, with possible beneficial effects for everything from arthritis to Alzheimer's disease.
Gang said medical researchers have identified regions in India with very low incidences of the two diseases.
They happen to be regions in which turmeric is most widely used in food preparation.
Scientists have isolated the main active ingredient in turmeric, curcumin, but Gang is also interested in two other compounds found in the rhizome of turmeric that have up to 100,000 times the anti-inflammatory potency of curcumin.
It's one of the reasons Gang believes it's more beneficial to actually eat the spices than it is to take supplements of isolated compounds, he said.
"I've always been more holistic when it comes to your health," he said. "You're better off using it as part of your diet than waiting till you get sick and taking a supplement," he said.
The fruits of the research Gang conducts could be many and varied. Working at Bio5, said Gang, gives him the opportunity to interact with researchers in other fields who might be able to make use of what he discovers.
One colleague is already looking to form a private company to develop pharmaceutical remedies from the compounds he isolates.
The research could also lead to targeted breeding of new varieties of plants, Gang said.
A chemist by training, he now combines biochemical analysis with genomics into a field called biochemical genomics.
Studying aromatic plants such as sweet basil, ginger and turmeric seems fruitful, said Gang, because the substances that have anti-oxidant, anti-inflammatory and even cancer-preventive properties are isolated in distinct sections of the plants, such as the rhizomes of ginger and turmeric.
Someday, products made from the fruits of Gang's research may cure what ails you. In the meantime, Gang suggests you simply spice up your meals.
● Contact reporter Tom Beal at 573-4158 or tbeal@azstarnet.com.
At the University of Arizona, where he is a professor in the Department of Plant Sciences, Gang grows turmeric and ginger plants in greenhouses on the roof of a parking garage on East Sixth Street.
He raises basil plants in controlled chambers in the basement of the Bio5 Research Institute across campus.
At home, Gang sprinkles turmeric on just about everything he cooks, even adds it to fruit smoothies.
Turmeric, a staple of Indian cooking that gives curries their bright yellow color, doesn't flavor things all that much, he said. "The kids don't even notice it," he said.
Ginger and basil also figure in their diet. They taste good, Gang said, and they are good for you.
He knows ginger works. He's been chewing it for years since discovering that it eased an undiagnosable stomach ailment he developed during his graduate school years.
"It had a dramatic effect," he said. "I went from being sick every day to being well most of the time."
Gang said his recovery is part of the reason he decided to concentrate his research on learning how plants make the remarkable substances that modern scientists are just beginning to study for their healthful effects.
Knowledge of the properties is not new, Gang said. "Ayurvedic practitioners in India have known about them for thousands of years."
Gang and his group are trying to identify and uncover the distinct compounds that make them work.
Turmeric is hot in natural healing circles, having been reidentified in recent years as a potent anti-inflammatory, with possible beneficial effects for everything from arthritis to Alzheimer's disease.
Gang said medical researchers have identified regions in India with very low incidences of the two diseases.
They happen to be regions in which turmeric is most widely used in food preparation.
Scientists have isolated the main active ingredient in turmeric, curcumin, but Gang is also interested in two other compounds found in the rhizome of turmeric that have up to 100,000 times the anti-inflammatory potency of curcumin.
It's one of the reasons Gang believes it's more beneficial to actually eat the spices than it is to take supplements of isolated compounds, he said.
"I've always been more holistic when it comes to your health," he said. "You're better off using it as part of your diet than waiting till you get sick and taking a supplement," he said.
The fruits of the research Gang conducts could be many and varied. Working at Bio5, said Gang, gives him the opportunity to interact with researchers in other fields who might be able to make use of what he discovers.
One colleague is already looking to form a private company to develop pharmaceutical remedies from the compounds he isolates.
The research could also lead to targeted breeding of new varieties of plants, Gang said.
A chemist by training, he now combines biochemical analysis with genomics into a field called biochemical genomics.
Studying aromatic plants such as sweet basil, ginger and turmeric seems fruitful, said Gang, because the substances that have anti-oxidant, anti-inflammatory and even cancer-preventive properties are isolated in distinct sections of the plants, such as the rhizomes of ginger and turmeric.
Someday, products made from the fruits of Gang's research may cure what ails you. In the meantime, Gang suggests you simply spice up your meals.
● Contact reporter Tom Beal at 573-4158 or tbeal@azstarnet.com.
Tuesday, July 8, 2008
Behind-the-scenes peek at brain research
[Source: Erin Zlomek, The Arizona Republic] - Chunks of human brain tissue, the telltale grooves still visible, soak in 1,000 formaldehyde-filled plastic tubs in a closet at Sun City's Sun Health Research Institute. Next door, researchers poke paper-thin neck arteries with special instruments.
All are on display for anyone curious to peek. But it's worth noting that at some point, the ones peeking usually become the pokers and brain donors.
"More than 80 percent of (our visitors) are engaged in science enough that they want to contribute more, in whatever way, whether it be volunteering time or becoming involved in a clinical trial," institute spokesman Brian Browne said.
Those curious observers are partly responsible for the center's blockbuster 2007-08 year. The non-profit, which specializes in Alzheimer's disease, Parkinson's disease, arthritis and dementia research, finished a $5.5 million building expansion in April 2007.
The new digs allowed the institute to more than double its annual visitor capacity from about 545 in 2006-07 to 1,225 in 2007-08.
Because many visitors form relationships with the institute thereafter, this year's larger tour groups fast became a vehicle for bringing in contributions and fueling growth. The 90-minute guided visits are free, held the first Tuesday of each month. Tours require a reservation.
Once the new wing opened and larger tours started at 10515 W. Santa Fe Drive, monetary and body donations spiked nearly 50 percent.
The facility can now accommodate groups from six local high schools, compared with just two in the past. This has led to the addition of nine student interns.
Volunteerism peaked, too. The facility landed a handful of new volunteers, bringing its roster to about 20. Though the volunteer pool is modest, Browne said each must have highly specialized skills (many are retired nurses and physicians), making any new addition a major accomplishment.
The institute's volunteer program was recently profiled by a Chinese government television station for a piece about recruiting skilled volunteers to work at the coming Beijing Olympic Games.
Browne also credits the increased interest to attention brought to Alzheimer's disease this year.
In June, Alzheimer's surpassed diabetes as the sixth leading cause of death in the country, according to the Centers for Disease Control and Prevention. That hits home in Arizona, where many retirees and seniors live.
Within a 10-mile radius of the institute, more than 8,000 people are living with the disease in Surprise, Sun City, Sun City West and Youngtown, said Deborah Schaus, executive director of the Alzheimer's Association Desert Southwest Chapter.
Still, not all guests who pass through the institute's doors are science aficionados, and some are uneasy when it comes to donating remains.
Sun City resident Ty Dale said that donating was a challenging decision when his family had medical power of attorney for his mother.
Dale's mother, Mary Elizabeth Dale, died of Alzheimer's in February. She was 78.
"Immediately after her death, they did the autopsy and harvested - though I hate that word - her brain," Dale said. "Mom was more than just a number. But who knows, it could benefit her grandkids one day if this disease turns out to be hereditary. I'll feel closure someday if something good comes from it."
All are on display for anyone curious to peek. But it's worth noting that at some point, the ones peeking usually become the pokers and brain donors.
"More than 80 percent of (our visitors) are engaged in science enough that they want to contribute more, in whatever way, whether it be volunteering time or becoming involved in a clinical trial," institute spokesman Brian Browne said.
Those curious observers are partly responsible for the center's blockbuster 2007-08 year. The non-profit, which specializes in Alzheimer's disease, Parkinson's disease, arthritis and dementia research, finished a $5.5 million building expansion in April 2007.
The new digs allowed the institute to more than double its annual visitor capacity from about 545 in 2006-07 to 1,225 in 2007-08.
Because many visitors form relationships with the institute thereafter, this year's larger tour groups fast became a vehicle for bringing in contributions and fueling growth. The 90-minute guided visits are free, held the first Tuesday of each month. Tours require a reservation.
Once the new wing opened and larger tours started at 10515 W. Santa Fe Drive, monetary and body donations spiked nearly 50 percent.
The facility can now accommodate groups from six local high schools, compared with just two in the past. This has led to the addition of nine student interns.
Volunteerism peaked, too. The facility landed a handful of new volunteers, bringing its roster to about 20. Though the volunteer pool is modest, Browne said each must have highly specialized skills (many are retired nurses and physicians), making any new addition a major accomplishment.
The institute's volunteer program was recently profiled by a Chinese government television station for a piece about recruiting skilled volunteers to work at the coming Beijing Olympic Games.
Browne also credits the increased interest to attention brought to Alzheimer's disease this year.
In June, Alzheimer's surpassed diabetes as the sixth leading cause of death in the country, according to the Centers for Disease Control and Prevention. That hits home in Arizona, where many retirees and seniors live.
Within a 10-mile radius of the institute, more than 8,000 people are living with the disease in Surprise, Sun City, Sun City West and Youngtown, said Deborah Schaus, executive director of the Alzheimer's Association Desert Southwest Chapter.
Still, not all guests who pass through the institute's doors are science aficionados, and some are uneasy when it comes to donating remains.
Sun City resident Ty Dale said that donating was a challenging decision when his family had medical power of attorney for his mother.
Dale's mother, Mary Elizabeth Dale, died of Alzheimer's in February. She was 78.
"Immediately after her death, they did the autopsy and harvested - though I hate that word - her brain," Dale said. "Mom was more than just a number. But who knows, it could benefit her grandkids one day if this disease turns out to be hereditary. I'll feel closure someday if something good comes from it."
Local brain specialist shortage finds relief
[Source: HEIDI ROWLEY, Tucson Citizen] - Tucson-area residents suffering from excruciating back pain or migraines, Alzheimer’s or Parkinson’s, multiple sclerosis or seizures may wait months to see a local brain or spinal cord specialist.
For those who need immediate care for a brain or spinal injury after a car accident or other life-threatening emergency, often the only option is helicopter transport to Phoenix, San Diego or Las Vegas, because either no on-call neurological specialist or space is available at a Tucson hospital.
Hundreds of patients are sent out of the Tucson area every year for treatment of nervous system illnesses and injuries, said Greg Angle, chief executive at St. Joseph Hospital. Some rural southern Arizona hospitals are bypassing the Old Pueblo, by sending patients to Phoenix because of Tucson's shortage of neurologists and neurosurgeons.
"We've not done a good job in Tucson in providing this service," Angle said.
That is changing.
• The Center for Neurosciences opened in March at 2450 E. River Road.
The center touts six neurosurgeons, four neurologists and high-tech diagnostic tools to provide more coordinated and convenient outpatient care. Its team, who had practiced in five offices citywide, includes Tucson's only pediatric neurosurgeons and neuro-oncologist.
The effort has attracted two more neurological specialists to Tucson, neurosurgeon Abhay Sanan said.
"We've had to struggle for years for someone to join us," Sanan said.
• The Carondelet Neurological Institute, a collaboration between Carondelet and a medical practice group, Western Neurosurgery, opened 42 beds in May exclusively for neurological patients. The institute is on the fifth floor of St. Joseph Hospital's new Women's Pavilion at 350 N. Wilmot Road.
Intensive-care rooms and three state-of-the-art operating suites will be completed by fall.
The institute will offer the most comprehensive inpatient neurological services, Angle said, and will have neurosurgeons and neurologists on call all day, every day.
"The gem is not the new technology," neurosurgeon Matthew Wilson said. "It's the 24-hour coverage."
• Tucson Medical Center has been designated a Neuroscience Center of Excellence by the health care consulting and assessment company NeuStrategy Inc., which is based in Chicago.
TMC has two neurosciences operating rooms, an eight-bed neurointensive observation unit, a 37-bed neuronursing unit, epilepsy monitoring units for adults and children and a sleep diagnostics lab. The center offers nurses six months of training to understand neurology patients.
Specialist, bed shortages
Nationwide, the pool of neurosurgeons has been shrinking. A study by the American Association of Neurological Surgeons counted 3,050 in 2004, down from 3,100 in 1991 and 3,400 neurosurgeons in 1997. The association does not have more-recent numbers.
An Arizona physician work force study found only 20 neurosurgeons working in Tucson in 2005, the most-recent year for which numbers are available.
Wilson, who started working in Tucson that year, was surprised there were not enough neurosurgeons to cover emergencies at Tucson's hospitals while responding to daily patient needs.
Even now, Wilson said, only one surgeon is available on call many nights to cover Tucson's seven hospitals.
Tucson's neurology specialists, no matter which hospital or practice group they belong to, take turns being on call at Tucson's emergency rooms and most will continue to do so after the Carondelet institute's opening. Both Sanan and fellow neurosurgeon Eric Sipos, director of the institute, said they would eventually like to focus on one or two hospitals, but neither has established a timeline for doing so.
When a blood clot formed in Manuel Moreno's brain in November 2006, the Tucson bishop was sent to Phoenix, not because of a lack of neurosurgeons to treat him but because there were no beds available at the local hospitals where the specialists were working, Sipos said.
It was Moreno's health crisis and subsequent death that galvanized local doctors and specialists to focus on the need for more neurosurgeons and beds for their patients.
Efforts drawing praise
Patients are praising the results.
Leona "Lee" Schnebly, 75, had back surgery June 10 at St. Joseph's Hospital to repair damaged disks causing immense pain and then stayed in one of the new beds at the Carondelet Neurological Institute.
"I've had surgery before, but it's never been this pleasant," she said the day after Wilson removed bone and inserted titanium screws. "I'm amazed and so glad."
Schnebly was impressed by the attentive and caring staff, and she loved her spacious, private recovery room.
Sierra Vista couple Robert Jamison, 49, and wife Lucy, 47, appreciate the convenience that the Center for Neurosciences' centralized care provides.
Three days after Robert Jamison's terminal brain cancer was diagnosed in May 2007, Sanan removed a large tumor at St. Mary's Hospital.
Lucy Jamison said scheduling appointments and medical services her husband needed after his surgery was challenging because the doctors and services were in different offices.
Now, Jamison sees both Sanan and Dr. Michael Badruddoja, Tucson's only neuro-oncologist, and gets the tests he needs at the same place.
Center for Neurosciences' coordination reduces the stress on those facing terminal cancer.
Sipos, director of the Carondelet Neurological Institute, said a new Western Neurosurgery building under construction near the institute will also provide outpatient services.
Tucson lures more doctors
The developments here are making Tucson more attractive to neurological specialists.
Dr. Dave Teeple, an epilepsy specialist from the Barrows Institute in Phoenix, is one of the specialists joining the Center for Neurosciences. The other is a neurosurgeon from the Mayo Clinic in Phoenix.
Teeple, a neurologist who grew up in Tucson, said he will be on call at St. Mary's Hospital and TMC and will be in charge of running an adult epileptic monitoring center at the latter.
"There is a need for epilepsy specialists down there," he said last week from Phoenix. "There is a monthslong waiting list to see an epileptologist."
Teeple will start in mid-July.
Carondelet Neurological Institute is also recruiting.
"We're seeing improvement as the word about what we are doing has gotten out there," Sipos said. "We're seeing some very strong applicants. As we have neared completion, the interest is escalating."
Sipos hopes to hire stroke and spinal care specialists.
"I'm feeling more optimistic about neurologists and neurosurgeons in this town than I ever have. It is still a concern, but a big part of what we're doing is making that problem go away."
For those who need immediate care for a brain or spinal injury after a car accident or other life-threatening emergency, often the only option is helicopter transport to Phoenix, San Diego or Las Vegas, because either no on-call neurological specialist or space is available at a Tucson hospital.
Hundreds of patients are sent out of the Tucson area every year for treatment of nervous system illnesses and injuries, said Greg Angle, chief executive at St. Joseph Hospital. Some rural southern Arizona hospitals are bypassing the Old Pueblo, by sending patients to Phoenix because of Tucson's shortage of neurologists and neurosurgeons.
"We've not done a good job in Tucson in providing this service," Angle said.
That is changing.
• The Center for Neurosciences opened in March at 2450 E. River Road.
The center touts six neurosurgeons, four neurologists and high-tech diagnostic tools to provide more coordinated and convenient outpatient care. Its team, who had practiced in five offices citywide, includes Tucson's only pediatric neurosurgeons and neuro-oncologist.
The effort has attracted two more neurological specialists to Tucson, neurosurgeon Abhay Sanan said.
"We've had to struggle for years for someone to join us," Sanan said.
• The Carondelet Neurological Institute, a collaboration between Carondelet and a medical practice group, Western Neurosurgery, opened 42 beds in May exclusively for neurological patients. The institute is on the fifth floor of St. Joseph Hospital's new Women's Pavilion at 350 N. Wilmot Road.
Intensive-care rooms and three state-of-the-art operating suites will be completed by fall.
The institute will offer the most comprehensive inpatient neurological services, Angle said, and will have neurosurgeons and neurologists on call all day, every day.
"The gem is not the new technology," neurosurgeon Matthew Wilson said. "It's the 24-hour coverage."
• Tucson Medical Center has been designated a Neuroscience Center of Excellence by the health care consulting and assessment company NeuStrategy Inc., which is based in Chicago.
TMC has two neurosciences operating rooms, an eight-bed neurointensive observation unit, a 37-bed neuronursing unit, epilepsy monitoring units for adults and children and a sleep diagnostics lab. The center offers nurses six months of training to understand neurology patients.
Specialist, bed shortages
Nationwide, the pool of neurosurgeons has been shrinking. A study by the American Association of Neurological Surgeons counted 3,050 in 2004, down from 3,100 in 1991 and 3,400 neurosurgeons in 1997. The association does not have more-recent numbers.
An Arizona physician work force study found only 20 neurosurgeons working in Tucson in 2005, the most-recent year for which numbers are available.
Wilson, who started working in Tucson that year, was surprised there were not enough neurosurgeons to cover emergencies at Tucson's hospitals while responding to daily patient needs.
Even now, Wilson said, only one surgeon is available on call many nights to cover Tucson's seven hospitals.
Tucson's neurology specialists, no matter which hospital or practice group they belong to, take turns being on call at Tucson's emergency rooms and most will continue to do so after the Carondelet institute's opening. Both Sanan and fellow neurosurgeon Eric Sipos, director of the institute, said they would eventually like to focus on one or two hospitals, but neither has established a timeline for doing so.
When a blood clot formed in Manuel Moreno's brain in November 2006, the Tucson bishop was sent to Phoenix, not because of a lack of neurosurgeons to treat him but because there were no beds available at the local hospitals where the specialists were working, Sipos said.
It was Moreno's health crisis and subsequent death that galvanized local doctors and specialists to focus on the need for more neurosurgeons and beds for their patients.
Efforts drawing praise
Patients are praising the results.
Leona "Lee" Schnebly, 75, had back surgery June 10 at St. Joseph's Hospital to repair damaged disks causing immense pain and then stayed in one of the new beds at the Carondelet Neurological Institute.
"I've had surgery before, but it's never been this pleasant," she said the day after Wilson removed bone and inserted titanium screws. "I'm amazed and so glad."
Schnebly was impressed by the attentive and caring staff, and she loved her spacious, private recovery room.
Sierra Vista couple Robert Jamison, 49, and wife Lucy, 47, appreciate the convenience that the Center for Neurosciences' centralized care provides.
Three days after Robert Jamison's terminal brain cancer was diagnosed in May 2007, Sanan removed a large tumor at St. Mary's Hospital.
Lucy Jamison said scheduling appointments and medical services her husband needed after his surgery was challenging because the doctors and services were in different offices.
Now, Jamison sees both Sanan and Dr. Michael Badruddoja, Tucson's only neuro-oncologist, and gets the tests he needs at the same place.
Center for Neurosciences' coordination reduces the stress on those facing terminal cancer.
Sipos, director of the Carondelet Neurological Institute, said a new Western Neurosurgery building under construction near the institute will also provide outpatient services.
Tucson lures more doctors
The developments here are making Tucson more attractive to neurological specialists.
Dr. Dave Teeple, an epilepsy specialist from the Barrows Institute in Phoenix, is one of the specialists joining the Center for Neurosciences. The other is a neurosurgeon from the Mayo Clinic in Phoenix.
Teeple, a neurologist who grew up in Tucson, said he will be on call at St. Mary's Hospital and TMC and will be in charge of running an adult epileptic monitoring center at the latter.
"There is a need for epilepsy specialists down there," he said last week from Phoenix. "There is a monthslong waiting list to see an epileptologist."
Teeple will start in mid-July.
Carondelet Neurological Institute is also recruiting.
"We're seeing improvement as the word about what we are doing has gotten out there," Sipos said. "We're seeing some very strong applicants. As we have neared completion, the interest is escalating."
Sipos hopes to hire stroke and spinal care specialists.
"I'm feeling more optimistic about neurologists and neurosurgeons in this town than I ever have. It is still a concern, but a big part of what we're doing is making that problem go away."
Monday, June 23, 2008
Medivation Initiates Second Pivotal Phase 3 Trial Of Dimebon™ In Patients With Alzheimer's Disease
[Source: Genome Web News] - Medivation, Inc. (NASDAQ: MDVN) announced it has initiated dosing of patients in its second pivotal Phase 3 trial of the investigational drug Dimebon™ in patients with mild-to-moderate Alzheimer's disease (AD). The international, double-blind, placebo-controlled safety and efficacy study of oral Dimebon is known as the CONNECTION study.
"We saw very encouraging results in our first pivotal trial, in which Dimebon demonstrated statistically significant improvements over placebo on all five efficacy endpoints at both six months and at one year. We look forward to confirming the efficacy and safety of Dimebon in the CONNECTION study," said Lynn Seely, M.D., Chief Medical Officer of Medivation. "The initiation of this study brings us a major step closer to our goal of obtaining regulatory approval for Dimebon. We are working to bring this investigational drug to market as quickly as possible to address the unmet medical need in Alzheimer's disease and bring hope to patients and caregivers."
The U.S. Food and Drug Administration (FDA) has informed Medivation that the CONNECTION study together with the previously completed pivotal trial can be used to support the approval of Dimebon to treat mild-to-moderate Alzheimer's disease, as long as a significant proportion of the sites in the CONNECTION study are located in the United States. Medivation expects to complete the CONNECTION study and apply for U.S. and European marketing approval in 2010.
Design of CONNECTION Study
The CONNECTION study will enroll approximately 525 patients with mild-to-moderate Alzheimer's disease at approximately 100 sites in the United States, Europe and South America. Patients will be randomized to one of three treatment groups: Dimebon 20 mg three times per day, Dimebon 5 mg three times per day or placebo. Patients may not be taking any other Alzheimer's disease drugs during the trial. After completing six months of treatment, all patients - including those randomized to placebo - will be offered the opportunity to receive Dimebon in an extension trial until marketing authorization.
The primary endpoints of the trial are the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change plus caregiver interview (CIBIC-plus). These are the two endpoints that have been accepted by the FDA to support registration of all approved drugs for Alzheimer's disease.
Pierre Tariot, M.D., Director, Memory Disorders Center, Banner Alzheimer's Institute. "There is an urgent need for new treatments for a disease with such devastating effects on the quality of life of patients and their caregivers. Dimebon represents an innovative form of therapy that may have the potential to ameliorate symptoms and possibly improve the course of Alzheimer's disease. It is crucial that it be fully assessed as rapidly as possible."
For more information on the CONNECTION study, please visit
http://www.connectionstudy.com.
Results of First Pivotal Phase 3 Trial
Medivation previously announced results from its first pivotal trial of Dimebon in 183 patients with mild-to-moderate Alzheimer's disease, which showed that Dimebon improved the clinical course of Alzheimer's disease by demonstrating statistically significant improvements over placebo in each of the five primary aspects of the disease - memory, thinking, activities of daily living, behavior and overall clinical function. Significant gains over placebo were evident after as little as 12 weeks of treatment, and were maintained after both six months and a full year of treatment. Importantly, overall benefit compared to placebo continued to increase over time, and was larger at one year than at six months. Dimebon was well-tolerated throughout the entire one-year treatment period. The majority of adverse events were mild. Dry mouth (18.0 percent Dimebon, 1.1 percent placebo) and depressed mood were the most common events. Patients treated with Dimebon experienced significantly fewer serious adverse events than those treated with placebo at one year.
"We saw very encouraging results in our first pivotal trial, in which Dimebon demonstrated statistically significant improvements over placebo on all five efficacy endpoints at both six months and at one year. We look forward to confirming the efficacy and safety of Dimebon in the CONNECTION study," said Lynn Seely, M.D., Chief Medical Officer of Medivation. "The initiation of this study brings us a major step closer to our goal of obtaining regulatory approval for Dimebon. We are working to bring this investigational drug to market as quickly as possible to address the unmet medical need in Alzheimer's disease and bring hope to patients and caregivers."
The U.S. Food and Drug Administration (FDA) has informed Medivation that the CONNECTION study together with the previously completed pivotal trial can be used to support the approval of Dimebon to treat mild-to-moderate Alzheimer's disease, as long as a significant proportion of the sites in the CONNECTION study are located in the United States. Medivation expects to complete the CONNECTION study and apply for U.S. and European marketing approval in 2010.
Design of CONNECTION Study
The CONNECTION study will enroll approximately 525 patients with mild-to-moderate Alzheimer's disease at approximately 100 sites in the United States, Europe and South America. Patients will be randomized to one of three treatment groups: Dimebon 20 mg three times per day, Dimebon 5 mg three times per day or placebo. Patients may not be taking any other Alzheimer's disease drugs during the trial. After completing six months of treatment, all patients - including those randomized to placebo - will be offered the opportunity to receive Dimebon in an extension trial until marketing authorization.
The primary endpoints of the trial are the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change plus caregiver interview (CIBIC-plus). These are the two endpoints that have been accepted by the FDA to support registration of all approved drugs for Alzheimer's disease.
Pierre Tariot, M.D., Director, Memory Disorders Center, Banner Alzheimer's Institute. "There is an urgent need for new treatments for a disease with such devastating effects on the quality of life of patients and their caregivers. Dimebon represents an innovative form of therapy that may have the potential to ameliorate symptoms and possibly improve the course of Alzheimer's disease. It is crucial that it be fully assessed as rapidly as possible."
For more information on the CONNECTION study, please visit
http://www.connectionstudy.com.
Results of First Pivotal Phase 3 Trial
Medivation previously announced results from its first pivotal trial of Dimebon in 183 patients with mild-to-moderate Alzheimer's disease, which showed that Dimebon improved the clinical course of Alzheimer's disease by demonstrating statistically significant improvements over placebo in each of the five primary aspects of the disease - memory, thinking, activities of daily living, behavior and overall clinical function. Significant gains over placebo were evident after as little as 12 weeks of treatment, and were maintained after both six months and a full year of treatment. Importantly, overall benefit compared to placebo continued to increase over time, and was larger at one year than at six months. Dimebon was well-tolerated throughout the entire one-year treatment period. The majority of adverse events were mild. Dry mouth (18.0 percent Dimebon, 1.1 percent placebo) and depressed mood were the most common events. Patients treated with Dimebon experienced significantly fewer serious adverse events than those treated with placebo at one year.
Tuesday, June 10, 2008
Banner, Sun Health institutes seeks patients for Alzheimer's study
{source: Phoenix Business Journal} - Banner Alzheimer's Institute and Sun Health Research Institute are enrolling patients in a study of the investigational drug Dimebon for the treatment of Alzheimer's disease.
The study will evaluate the safety and effect of Dimebon taken in combination with Aricept, an FDA-approved Alzheimer's treatment. Results from a one-year study of Dimebon -- showing significant improvements in memory, thinking, function and behavior -- were highlighted at the recent 2008 Arizona Alzheimer's Consortium Annual Conference. Both Banner Alzheimer's Institute and Sun Health Research Institute are members of the group.
More than 5 million people in the U.S. are living with Alzheimer's disease, according to the Alzheimer's Association. It is a progressive neurodegenerative disease that destroys brain cells and affects areas of the brain involved in memory, cognition, judgment, language and behavior. Currently available therapies treat the symptoms with modest effect in most patients, according to researchers.
"We are encouraged by the results Dimebon has shown in clinical studies to date and believe it is imperative to fully assess its promise in the fight against Alzheimer's disease," said Dr. Pierre N. Tariot, director of the Memory Disorders Center at Banner Alzheimer's Institute, in a statement.
Patients 50 and older with a clinical diagnosis of Alzheimer's disease and taking Aricept for at least 60 days may be eligible to participate in the study.
For more: Banner Alzheimer's Institute, 602-239-6900; Sun Health Research Institute, 623-875-6500; www.shri.org.
The study will evaluate the safety and effect of Dimebon taken in combination with Aricept, an FDA-approved Alzheimer's treatment. Results from a one-year study of Dimebon -- showing significant improvements in memory, thinking, function and behavior -- were highlighted at the recent 2008 Arizona Alzheimer's Consortium Annual Conference. Both Banner Alzheimer's Institute and Sun Health Research Institute are members of the group.
More than 5 million people in the U.S. are living with Alzheimer's disease, according to the Alzheimer's Association. It is a progressive neurodegenerative disease that destroys brain cells and affects areas of the brain involved in memory, cognition, judgment, language and behavior. Currently available therapies treat the symptoms with modest effect in most patients, according to researchers.
"We are encouraged by the results Dimebon has shown in clinical studies to date and believe it is imperative to fully assess its promise in the fight against Alzheimer's disease," said Dr. Pierre N. Tariot, director of the Memory Disorders Center at Banner Alzheimer's Institute, in a statement.
Patients 50 and older with a clinical diagnosis of Alzheimer's disease and taking Aricept for at least 60 days may be eligible to participate in the study.
For more: Banner Alzheimer's Institute, 602-239-6900; Sun Health Research Institute, 623-875-6500; www.shri.org.
Monday, June 9, 2008
Sygnis Pharma Buys TGen Spin-out Amnestix for $6.3M
[Source: a GenomeWeb staff reporter ] - German drug developer Sygnis Pharma has bought Amnestix, a spin-out from the Translational Genomics Research Institute, for €4 million ($6.3 million) in a cash and shares deal, Sygnis said today.
Amnestix, which was started by TGen researchers Dietrich Stephan and Matthew Huentelman in 2006 and was funded by the Brain Trust Accelerator Fund, is focused on developing therapeutics that can improve cognition and memory functions that are damaged by neurological diseases.
Amnestix has discovered a series of genes and pathways involved in memory performance through whole-genome association analysis. The company has also found novel uses for protein kinase inhibitors that it believes could be used to treat conditions such as cognitive impairment and dementia.
Sygnis plans to continue to develop these compounds for use in treating age-related memory problems, Alzheimer’s disease, and other neurological diseases. Sygnis also said that the deal gives it access to some TGen projects that are focused on central nervous system disorders.
Amnestix CEO Karoly Nikolich will remain with the company and will help Sygnis expand its partnering, scientific, and financial networking.
Amnestix, which was started by TGen researchers Dietrich Stephan and Matthew Huentelman in 2006 and was funded by the Brain Trust Accelerator Fund, is focused on developing therapeutics that can improve cognition and memory functions that are damaged by neurological diseases.
Amnestix has discovered a series of genes and pathways involved in memory performance through whole-genome association analysis. The company has also found novel uses for protein kinase inhibitors that it believes could be used to treat conditions such as cognitive impairment and dementia.
Sygnis plans to continue to develop these compounds for use in treating age-related memory problems, Alzheimer’s disease, and other neurological diseases. Sygnis also said that the deal gives it access to some TGen projects that are focused on central nervous system disorders.
Amnestix CEO Karoly Nikolich will remain with the company and will help Sygnis expand its partnering, scientific, and financial networking.
Tuesday, June 3, 2008
TGen Researcher Receives the Young Investigator Award from the Arizona Alzheimer’s Consortium
[Source: TGen] - Dr. Matthew Huentelman honored for his contributions to Alzheimer's disease and aging research.
Dr. Matthew Huentelman, an Associate Investigator in the Neurogenomics Division at the Translational Genomics Research Institute (TGen), was the recipient of the Young Investigator Award from the Arizona Alzheimer’s Consortium. Dr. Huentelman was recognized for his pioneering accomplishments in Alzheimer’s disease research and for being an outstanding mentor to his research team and students.
"The Arizona Alzheimer's Consortium is extremely proud of Matt. He has already made significant contributions to the genetic understanding of memory and Alzheimer's disease, and to the discovery of promising memory-enhancing treatments. Matt's know-how and accomplishments, his dedication, hard work and enthusiasm, and his mentoring skills and collaborative spirit are examples for us all," said Dr. Eric Reiman, Director, Arizona Alzheimer's Consortium.
The Young Investigator Award is given annually to a young investigator in Arizona for their contributions to Alzheimer's disease and aging research. The selection process for the Young Investigator Award is extremely competitive. Each candidate is evaluated by the Arizona Alzheimer's Consortium's Internal Scientific Advisory Board, which consists of 25 researchers from the organization's seven institutional members.
"I really value my relationship with the Arizona Alzheimer's Consortium. There are many excellent young investigators within the Consortium, and I consider it a great honor to receive this award,” said Dr. Huentelman.
Dr. Huentelman received a plaque and a $5,000 research grant to continue his work in memory research. He accepted the award at the Consortium's annual meeting attended by fellow researchers, members of the community, the Consortium's Internal and External Advisory Boards, and the meeting's keynote speaker, Dr. David Holtzman, the Andrew B. and Gretchen P. Jones Professor and Chairman of the Department of Neurology at the Washington University School of Medicine.
"This is an outstanding honor for a terrific young scientist whose efforts are moving this field forward in remarkable ways,” said TGen President Dr. Jeffrey Trent.
Currently, Dr. Huentelman is using genetic technologies to study a gene called KIBRA, which plays a significant role in memory performance in humans. Dr. Huentelman has received grants from the National Institutes of Health and Science Foundation Arizona to continue this work with the hope of developing promising new Alzheimer's disease treatments.
Dr. Huentelman joined TGen in July of 2004 after completing his doctoral work at the University of Florida's Department of Physiology and Functional Genomics where he investigated the application of gene therapy in the study of hypertension. His undergraduate degree is from Ohio University's Department of Chemistry and Biochemistry. Dr. Huentelman's career includes visiting researcher stints in Moscow, Russia at the prestigious Lomonosov Moscow State University and in the United Kingdom at the University of Bristol. At present time he has published over 25 peer-reviewed manuscripts in the scientific literature.
The Arizona Alzheimer's Consortium is the nation’s leading model of statewide collaboration in Alzheimer's disease research. Established in 1998, the Consortium capitalizes on its participating institutions' complementary strengths in brain imaging computer science, genomics, the basic and cognitive neurosciences and clinical and neuropathology research to promote the scientific understanding and early detection of Alzheimer's disease and find effective disease-stopping and prevention therapies. It also seeks to educate Arizona residents about Alzheimer's disease, research progress in the state and the resources needed to help patients, families and professionals manage the disease. The Consortium is determined to find effective treatments to halt the progression and prevent the onset of Alzheimer's disease in the next 12 years
Dr. Matthew Huentelman, an Associate Investigator in the Neurogenomics Division at the Translational Genomics Research Institute (TGen), was the recipient of the Young Investigator Award from the Arizona Alzheimer’s Consortium. Dr. Huentelman was recognized for his pioneering accomplishments in Alzheimer’s disease research and for being an outstanding mentor to his research team and students.
"The Arizona Alzheimer's Consortium is extremely proud of Matt. He has already made significant contributions to the genetic understanding of memory and Alzheimer's disease, and to the discovery of promising memory-enhancing treatments. Matt's know-how and accomplishments, his dedication, hard work and enthusiasm, and his mentoring skills and collaborative spirit are examples for us all," said Dr. Eric Reiman, Director, Arizona Alzheimer's Consortium.
The Young Investigator Award is given annually to a young investigator in Arizona for their contributions to Alzheimer's disease and aging research. The selection process for the Young Investigator Award is extremely competitive. Each candidate is evaluated by the Arizona Alzheimer's Consortium's Internal Scientific Advisory Board, which consists of 25 researchers from the organization's seven institutional members.
"I really value my relationship with the Arizona Alzheimer's Consortium. There are many excellent young investigators within the Consortium, and I consider it a great honor to receive this award,” said Dr. Huentelman.
Dr. Huentelman received a plaque and a $5,000 research grant to continue his work in memory research. He accepted the award at the Consortium's annual meeting attended by fellow researchers, members of the community, the Consortium's Internal and External Advisory Boards, and the meeting's keynote speaker, Dr. David Holtzman, the Andrew B. and Gretchen P. Jones Professor and Chairman of the Department of Neurology at the Washington University School of Medicine.
"This is an outstanding honor for a terrific young scientist whose efforts are moving this field forward in remarkable ways,” said TGen President Dr. Jeffrey Trent.
Currently, Dr. Huentelman is using genetic technologies to study a gene called KIBRA, which plays a significant role in memory performance in humans. Dr. Huentelman has received grants from the National Institutes of Health and Science Foundation Arizona to continue this work with the hope of developing promising new Alzheimer's disease treatments.
Dr. Huentelman joined TGen in July of 2004 after completing his doctoral work at the University of Florida's Department of Physiology and Functional Genomics where he investigated the application of gene therapy in the study of hypertension. His undergraduate degree is from Ohio University's Department of Chemistry and Biochemistry. Dr. Huentelman's career includes visiting researcher stints in Moscow, Russia at the prestigious Lomonosov Moscow State University and in the United Kingdom at the University of Bristol. At present time he has published over 25 peer-reviewed manuscripts in the scientific literature.
The Arizona Alzheimer's Consortium is the nation’s leading model of statewide collaboration in Alzheimer's disease research. Established in 1998, the Consortium capitalizes on its participating institutions' complementary strengths in brain imaging computer science, genomics, the basic and cognitive neurosciences and clinical and neuropathology research to promote the scientific understanding and early detection of Alzheimer's disease and find effective disease-stopping and prevention therapies. It also seeks to educate Arizona residents about Alzheimer's disease, research progress in the state and the resources needed to help patients, families and professionals manage the disease. The Consortium is determined to find effective treatments to halt the progression and prevent the onset of Alzheimer's disease in the next 12 years
Alzheimer's conference draws massive crowd
[Source: Joy Slagowski, http://www.yourwestvalley.com/] - If conference attendance is a measure of the impact Alzheimer's disease has on a community, the effect of the disease on Arizona is staggering.
At Friday's Arizona's Alzheimer's Consortium 2008 annual conference, nearly 900 researchers, health care providers, caregivers, families and patients filled the conference room at Renaissance Glendale Hotel & Spa. Presentations geared to the general public were given in the morning, and scientific discussions took place in the afternoon.
The consortium is a statewide collaboration of 150 researchers from seven institutions: Sun Health Research Institute, Arizona State University, the Barrow Neurological Institute, Mayo Clinic Scottsdale, Translational Genomics Research Institute, University of Arizona, and the Banner Alzheimer's Institute.
Charles Borwege, 71, of Sun City West attended the event to learn more about the disease that his wife, Nancy, was diagnosed with two years ago.
He said he works on controlling emotions and nerves.
"I need to learn to relax," Borwege said.
Borwege said he got a lot out of a presentation given by Dr. Marisa Menchola on the emotional life of care giving.
Menchola said there were 9.8 million Americans providing at least 16 hours unpaid care for family members or friends who have dementia, at an economic cost of $8.5 billion dollars annually.
In Arizona, 175,000 residents are caregivers.
Addressing the mental and physical health issues related to care giving is crucial, Menchola said.
"Care giving implies not taking care of one, but two people," Menchola said. "Even when you are on a plane, the directions are if the oxygen mask drops to put yours on first - it's the same principle. If you pass out, you both are in deep trouble."
Caregivers need to understand the root causes of their emotions.
"Emotions are telling you something is going on in your life or your mind," Menchola said. "Don't try to ignore your emotions, pay attention closely."
Audience members queried a panel of doctors and social workers with a variety of questions.
Dr. Marwan Sabbagh, of the Sun Health Research Institute, addressed a question about spinal tap research, which he said will become even more prevalent in the future.
"Spinal tap fluid is one of the best proxy markers for (detecting bio-markers), better than blood," Sabbagh said.
Dr. Rena Li, a researcher with the Sun Health Research Institute who focuses on the connection between women's hormones and Alzheimer's, inquired about plans for research on hormone replacement therapy.
Pierre Tariot of Banner Alzheimer's Institute said there needed to be more research conducted as projects in the past were considered unfinished business.
"There's quite a lot of suggestion and inclination that estrogen replacement therapy may improve cognition or may alter the fate of a woman's brain as she ages," Tariot said. "This hormonal storm that occurs, which is the window of vulnerability of peri-menopause, is probably when hormone replacement should be started."
Generating interest in pursuing that research is critical, Tariot said.
"If we work together, we could get needed funding," Tariot said. "And with the right degree of passion we can make it a public health priority."
Joy Slagowski may be reached at 623-876-2514, or jslagowski@yourwestvalley.com.
At Friday's Arizona's Alzheimer's Consortium 2008 annual conference, nearly 900 researchers, health care providers, caregivers, families and patients filled the conference room at Renaissance Glendale Hotel & Spa. Presentations geared to the general public were given in the morning, and scientific discussions took place in the afternoon.
The consortium is a statewide collaboration of 150 researchers from seven institutions: Sun Health Research Institute, Arizona State University, the Barrow Neurological Institute, Mayo Clinic Scottsdale, Translational Genomics Research Institute, University of Arizona, and the Banner Alzheimer's Institute.
Charles Borwege, 71, of Sun City West attended the event to learn more about the disease that his wife, Nancy, was diagnosed with two years ago.
He said he works on controlling emotions and nerves.
"I need to learn to relax," Borwege said.
Borwege said he got a lot out of a presentation given by Dr. Marisa Menchola on the emotional life of care giving.
Menchola said there were 9.8 million Americans providing at least 16 hours unpaid care for family members or friends who have dementia, at an economic cost of $8.5 billion dollars annually.
In Arizona, 175,000 residents are caregivers.
Addressing the mental and physical health issues related to care giving is crucial, Menchola said.
"Care giving implies not taking care of one, but two people," Menchola said. "Even when you are on a plane, the directions are if the oxygen mask drops to put yours on first - it's the same principle. If you pass out, you both are in deep trouble."
Caregivers need to understand the root causes of their emotions.
"Emotions are telling you something is going on in your life or your mind," Menchola said. "Don't try to ignore your emotions, pay attention closely."
Audience members queried a panel of doctors and social workers with a variety of questions.
Dr. Marwan Sabbagh, of the Sun Health Research Institute, addressed a question about spinal tap research, which he said will become even more prevalent in the future.
"Spinal tap fluid is one of the best proxy markers for (detecting bio-markers), better than blood," Sabbagh said.
Dr. Rena Li, a researcher with the Sun Health Research Institute who focuses on the connection between women's hormones and Alzheimer's, inquired about plans for research on hormone replacement therapy.
Pierre Tariot of Banner Alzheimer's Institute said there needed to be more research conducted as projects in the past were considered unfinished business.
"There's quite a lot of suggestion and inclination that estrogen replacement therapy may improve cognition or may alter the fate of a woman's brain as she ages," Tariot said. "This hormonal storm that occurs, which is the window of vulnerability of peri-menopause, is probably when hormone replacement should be started."
Generating interest in pursuing that research is critical, Tariot said.
"If we work together, we could get needed funding," Tariot said. "And with the right degree of passion we can make it a public health priority."
Joy Slagowski may be reached at 623-876-2514, or jslagowski@yourwestvalley.com.
Tuesday, May 6, 2008
Scientists present Alzheimer's research update at confab
[Source: www.yourwestvalley.com ] -Sun Health Research Institute and its partners in the Arizona Alzheimer’s Consortium will have a free conference for the public to learn about progress in the fight against Alzheimer’s disease from 8 a.m. to 5 p.m. May 30 at the Renaissance Glendale Hotel & Spa, 9495 W. Coyotes Blvd.
The 10th annual event will feature presentations by leading physicians, researchers and scientists. Speakers include Joseph Rogers, Ph.D., president of Sun Health Research Institute, and Dr. Marwan Sabbagh, director of the Cleo Roberts Center for Clinical Research at Sun Health Research Institute.
A free buffet breakfast and lunch will be provided. Seating is limited, and registration is required by visiting www.azalz.org or by calling 602-239-6901.
The morning program features a community awareness forum, "Facing Alzheimer’s Together," with a focus on:
• Advances in diagnosing Alzheimer’s disease.
• Providing emotional support for caregivers.
• Physician and caregiver panel discussion with audience question-and-answer session.
The afternoon program is structured as a scientific forum, and morning session attendees are welcome to say for the afternoon session, featuring:
• Keynote speaker.
• Poster presentations.
• "Data blitz" presentations.
Alzheimer’s disease is the seventh-leading cause of death in the U.S., afflicting one in 10 people older than 65.
Treatments are available that improve the quality of life for some people with Alzheimer’s. Investigative treatments are being studied in clinical trials, and scientists have discovered several genes associated with the disease.
In addition, techniques are available to help people caring for a loved one with the disease.
The 10th annual event will feature presentations by leading physicians, researchers and scientists. Speakers include Joseph Rogers, Ph.D., president of Sun Health Research Institute, and Dr. Marwan Sabbagh, director of the Cleo Roberts Center for Clinical Research at Sun Health Research Institute.
A free buffet breakfast and lunch will be provided. Seating is limited, and registration is required by visiting www.azalz.org or by calling 602-239-6901.
The morning program features a community awareness forum, "Facing Alzheimer’s Together," with a focus on:
• Advances in diagnosing Alzheimer’s disease.
• Providing emotional support for caregivers.
• Physician and caregiver panel discussion with audience question-and-answer session.
The afternoon program is structured as a scientific forum, and morning session attendees are welcome to say for the afternoon session, featuring:
• Keynote speaker.
• Poster presentations.
• "Data blitz" presentations.
Alzheimer’s disease is the seventh-leading cause of death in the U.S., afflicting one in 10 people older than 65.
Treatments are available that improve the quality of life for some people with Alzheimer’s. Investigative treatments are being studied in clinical trials, and scientists have discovered several genes associated with the disease.
In addition, techniques are available to help people caring for a loved one with the disease.
Tuesday, April 29, 2008
First Diagnostic Test For Alzheimer's And Parkinson's Disease On The Horizon
[Source:ScienceDaily] -A new blood test that can give an early diagnosis of neurodegenerative disease and distinguish between Parkinson's and Alzheimer's disease could be launched this summer, reports Marina Murphy in SCI's Chemistry & Industry magazine.
Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4."
"There is currently no diagnostic test for any neurodegenerative disease on the market -- diagnoses are currently based solely on a clinical diagnosis of symptoms," said chief executive, Steve Rash.
Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.
Although the test has been welcomed by Kieran Breen, director of research at the Parkinson's Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: "While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis."
Susan Sorensen, head of research at the UK Alzheimer's Society said: "There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer's disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.
"The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer's disease... Some suggest Alzheimer's, for example, is too complex to be identified in this way."
Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.
Note: (1) Expert Review of Proteomics 2008, 5(1), 1-8; Biochemical and Biophysical Research Communications 2006, 342, 1034-1039
Adapted from materials provided by Society of Chemical Industry, via EurekAlert!, a service of AAAS.
Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4."
"There is currently no diagnostic test for any neurodegenerative disease on the market -- diagnoses are currently based solely on a clinical diagnosis of symptoms," said chief executive, Steve Rash.
Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.
Although the test has been welcomed by Kieran Breen, director of research at the Parkinson's Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: "While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis."
Susan Sorensen, head of research at the UK Alzheimer's Society said: "There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer's disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.
"The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer's disease... Some suggest Alzheimer's, for example, is too complex to be identified in this way."
Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.
Note: (1) Expert Review of Proteomics 2008, 5(1), 1-8; Biochemical and Biophysical Research Communications 2006, 342, 1034-1039
Adapted from materials provided by Society of Chemical Industry, via EurekAlert!, a service of AAAS.
Tuesday, April 22, 2008
Experts get $6.6 mil for Alzheimer's work
[Source: Ken Alltucker, The Arizona Republic] - Scientists at Banner Alzheimer's Institute and the Mayo Clinic in Arizona have secured a $6.6 million federal grant to study the brains of people who carry a genetic risk for developing Alzheimer's disease.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
Monday, April 14, 2008
PET's Targeted Imaging May Lead to Earlier, More Accurate Diagnosis of Dementia and Alzheimer's Disease
[Source: Barbara Kram, DonMed] - Researchers involved in a large, multi-institutional study using positron emission tomography (PET) imaging with the radiotracer fluorodeoxyglucose (FDG) were able to classify different types of dementia with very high rates of success, raising hopes that dementia diagnoses may one day be made at earlier stages.
"Previously, scientists have been able to look only at the surface of the brain to differentiate various types of dementia," said Lisa Mosconi, Ph.D., assistant professor of psychiatry at the New York University School of Medicine. "With FDG PET, we were able to develop standardized disease-specific patterns from which we could correctly classify dementia more than 94 percent of the time."
The study, which was reported in the March issue of the Journal of Nuclear Medicine, measured the cerebral metabolic rate of glucose (CMRglc)-the amount of sugar the brain uses to fuel its activities-in various areas of the organ. A decrease in this rate is indicative of a loss of nerve cells and of dysfunction associated with dementia. Because FDG behaves like glucose when injected into the body, its location in the PET scans pinpointed the specific area where glucose utilization had fallen below normal levels as compared to an age-appropriate control group.
"Each type of dementia examined-Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB)-affects a different area of the brain. Based on where in the brain this decrease occurred, we were able to determine which type of dementia a patient had," Mosconi explained.
For instance, only AD patients have severe CMRglc reductions in the hippocampus (a part of the brain located deep in the organ and, prior to this study, unreachable for examination), whereas FTD patients have only mild abnormalities in the area and DLB patients have no hippocampal hypometabolism. "We believe that the ability to measure this embedded area in the brain will be important in identifying AD at an early stage," added Mosconi.
This is also the first study to use FDG PET to compare an early stage of dementia known as mild cognitive impairment (MCI) with dementing diseases other than AD. According to the researchers, the results suggest that the ability to detect differentiated uptake of glucose may result in earlier and more accurate diagnoses of MCI and better disease management.
"Because the incidence of these disorders is expected to increase dramatically as the baby-boomer generation ages, accurate diagnosis is extremely important-particularly at the early and mild stages of dementia when life-style changes and therapeutic interventions would be most effective," said Mosconi.
AD and other forms or dementia can take several years to progress to a debilitating stage, and a diagnosis based on FDG-PET assessments at the first sign of onset may improve the prognosis of MCI patients. "Early diagnosis may enable earlier treatment and empower people to plan for their future sooner, including financial and legal matters. It is also important for individuals at risk to take care of treatable risk factors, such as hypertension and high cholesterol levels," said Mosconi. "By changing their diet and increasing exercise, many MCI patients may deter dementia for years-perhaps even until more effective treatments are developed."
The study comprised 548 subjects and is the largest FDG PET study measuring brain metabolism in different dementing disorders to date. Researchers from PET centers in the United States and Europe were able to apply and share objective image analysis procedures easily, opening up the possibility that this diagnostic procedure could be adapted to a clinical setting.
Dementia is a general term for a progressive brain dysfunction that results in the loss of memory and other intellectual abilities serious enough to interfere with daily life. MCI patients demonstrate a decline of cognitive performance that is more pronounced than expected from age but not severe enough to meet criteria for dementia. The clinical course of these patients is challenging to forecast on the basis of clinical measures alone. Many diseases can result in a form of dementia, the most common one being AD, a progressive and fatal brain disease. According to the Alzheimer's Association, more than five million people in the United States have AD, and by 2050, that number could triple. Currently it is the seventh leading cause of death in the United States.
Co-authors of "Multicenter Standardized 18F-FDG PET Diagnosis of Mild Cognitive Impairment, Alzheimer's Disease, and Other Dementias" include Wai H. Tsui, New York University School of Medicine and the Nathan Kline Institute, New York, N.Y.; Karl Herholz, University of Manchester, Manchester, U.K.; Alberto Pupi, University of Florence, Florence, Italy; Alexander Drzezga, University of Munich, Munich, Germany; Giovanni Lucignani, University of Milan, Milan, Italy; Eric M. Reiman, Good Samaritan Banner Center, University of Arizona, Phoenix, Ariz.; Vjera Holthoff, University Hospital of Dresden, Dresden, Germany; Elke Kalbe, Medical Faculty, University of Cologne, Cologne, Germany; Sandro Sorbi, University of Florence, Florence, Italy; Janine Diehl-Schmid, University of Munich, Munich, Germany; Robert Perneczky University of Munich, Munich, Germany; Francesca Clerici, University of Milan, Milan, Italy; Richard Caselli, Arizona Center for Alzheimer's Disease Research, Phoenix, Ariz.; Bettina Beuthien-Baumann, PET-Center Dresden-Rossendorf and University Hospital of Dresden, Dresden, Germany; Alexander Kurz, University of Munich, Munich, Germany; and Satoshi Minoshima, University of Washington, Seattle, Wash.
"Previously, scientists have been able to look only at the surface of the brain to differentiate various types of dementia," said Lisa Mosconi, Ph.D., assistant professor of psychiatry at the New York University School of Medicine. "With FDG PET, we were able to develop standardized disease-specific patterns from which we could correctly classify dementia more than 94 percent of the time."
The study, which was reported in the March issue of the Journal of Nuclear Medicine, measured the cerebral metabolic rate of glucose (CMRglc)-the amount of sugar the brain uses to fuel its activities-in various areas of the organ. A decrease in this rate is indicative of a loss of nerve cells and of dysfunction associated with dementia. Because FDG behaves like glucose when injected into the body, its location in the PET scans pinpointed the specific area where glucose utilization had fallen below normal levels as compared to an age-appropriate control group.
"Each type of dementia examined-Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB)-affects a different area of the brain. Based on where in the brain this decrease occurred, we were able to determine which type of dementia a patient had," Mosconi explained.
For instance, only AD patients have severe CMRglc reductions in the hippocampus (a part of the brain located deep in the organ and, prior to this study, unreachable for examination), whereas FTD patients have only mild abnormalities in the area and DLB patients have no hippocampal hypometabolism. "We believe that the ability to measure this embedded area in the brain will be important in identifying AD at an early stage," added Mosconi.
This is also the first study to use FDG PET to compare an early stage of dementia known as mild cognitive impairment (MCI) with dementing diseases other than AD. According to the researchers, the results suggest that the ability to detect differentiated uptake of glucose may result in earlier and more accurate diagnoses of MCI and better disease management.
"Because the incidence of these disorders is expected to increase dramatically as the baby-boomer generation ages, accurate diagnosis is extremely important-particularly at the early and mild stages of dementia when life-style changes and therapeutic interventions would be most effective," said Mosconi.
AD and other forms or dementia can take several years to progress to a debilitating stage, and a diagnosis based on FDG-PET assessments at the first sign of onset may improve the prognosis of MCI patients. "Early diagnosis may enable earlier treatment and empower people to plan for their future sooner, including financial and legal matters. It is also important for individuals at risk to take care of treatable risk factors, such as hypertension and high cholesterol levels," said Mosconi. "By changing their diet and increasing exercise, many MCI patients may deter dementia for years-perhaps even until more effective treatments are developed."
The study comprised 548 subjects and is the largest FDG PET study measuring brain metabolism in different dementing disorders to date. Researchers from PET centers in the United States and Europe were able to apply and share objective image analysis procedures easily, opening up the possibility that this diagnostic procedure could be adapted to a clinical setting.
Dementia is a general term for a progressive brain dysfunction that results in the loss of memory and other intellectual abilities serious enough to interfere with daily life. MCI patients demonstrate a decline of cognitive performance that is more pronounced than expected from age but not severe enough to meet criteria for dementia. The clinical course of these patients is challenging to forecast on the basis of clinical measures alone. Many diseases can result in a form of dementia, the most common one being AD, a progressive and fatal brain disease. According to the Alzheimer's Association, more than five million people in the United States have AD, and by 2050, that number could triple. Currently it is the seventh leading cause of death in the United States.
Co-authors of "Multicenter Standardized 18F-FDG PET Diagnosis of Mild Cognitive Impairment, Alzheimer's Disease, and Other Dementias" include Wai H. Tsui, New York University School of Medicine and the Nathan Kline Institute, New York, N.Y.; Karl Herholz, University of Manchester, Manchester, U.K.; Alberto Pupi, University of Florence, Florence, Italy; Alexander Drzezga, University of Munich, Munich, Germany; Giovanni Lucignani, University of Milan, Milan, Italy; Eric M. Reiman, Good Samaritan Banner Center, University of Arizona, Phoenix, Ariz.; Vjera Holthoff, University Hospital of Dresden, Dresden, Germany; Elke Kalbe, Medical Faculty, University of Cologne, Cologne, Germany; Sandro Sorbi, University of Florence, Florence, Italy; Janine Diehl-Schmid, University of Munich, Munich, Germany; Robert Perneczky University of Munich, Munich, Germany; Francesca Clerici, University of Milan, Milan, Italy; Richard Caselli, Arizona Center for Alzheimer's Disease Research, Phoenix, Ariz.; Bettina Beuthien-Baumann, PET-Center Dresden-Rossendorf and University Hospital of Dresden, Dresden, Germany; Alexander Kurz, University of Munich, Munich, Germany; and Satoshi Minoshima, University of Washington, Seattle, Wash.
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