Anti-tau drug improves cognition, decreases tau tangles in Alzheimer's disease models

While clinical trial results are being released regarding drugs intended to decrease amyloid production - thought to contribute to decline in Alzheimer's disease - clinical trials of drugs targeting other disease proteins, such as tau, are in their initial phases.

21 july 2012--Penn Medicine research presented today at the 2012 Alzheimer's Association International Conference (AAIC) shows that an anti-tau treatment called epithilone D (EpoD) was effective in preventing and intervening the progress of Alzheimer's disease in animal models, improving neuron function and cognition, as well as decreasing tau pathology.

By targeting tau, the drug aims to stabilize microtubules, which help support and transport of essential nutrients and information between cells. When tau malfunctions, microtubules break and tau accumulates into tangles.

"This drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer's and other tau-based neurodegenerative diseases," said John Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. "In addition to drugs targeting amyloid, which may not work in advanced Alzheimer's disease, our hope is that this and other anti-tau drugs can be tested in people with Alzheimer's disease to determine whether stabilizing microtubules damaged by malfunctioning tau protein may improve clinical and pathological outcomes."

The drug, identified through Penn's Center for Neurodegenerative Disease Research (CNDR) Drug Discovery Program, was previously shown to prevent further neurological damage and improve cognitive performance in animal models*. The Penn research team includes senior investigator Bin Zhang, MD, and Kurt Brunden, PhD, director of Drug Discovery at CNDR.

More information: Bristol-Myers Squibb, who developed and owns the rights to the drug, has started enrolling patients into a phase I clinical trial in people with mild Alzheimer's disease.

Presentation: "Microtubule Stabilizing Drugs for Abrogation and Prevention of Alzheimer's Disease," during symposium on "Insights into Non-Alzheimer's Disease Dementia Also Inform Us About Alzheimer's Disease"

*Brunden, K.R., Zhang, B., Carroll, J., Yao, Y., Poduzak, J.S., Hogan, A.M., Iba, M., James, M.J., Xie, S., Ballatore, C., Smith, A.B., III, Lee, V.M-Y., and Trojanowski, J.Q. Epothilone D improves microtubule density, axonal integrity and cognition in a transgenic mouse model of tauopathy. J. Neurosci., 30: 13861-13866, 2010.

Provided by University of Pennsylvania School of Medicine

Research identifies link between Alzheimer's disease and diabetes

(Medical Xpress) -- Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ), collaborating with scientists from Northwestern University in Illinois, have provided direct experimental evidence that diabetes is linked to the onset of Alzheimer's disease. The study, published online this week in the Journal of Alzheimer's Disease, used an experimental model that shows potential as an important new tool for investigations of Alzheimer’s disease and of drugs being developed to treat Alzheimer’s.

20 july 2012--UMDNJ researchers Peter Frederikse, PhD, and Chinnaswamy Kasinathan, PhD, collaborated with William Klein, PhD, at Northwestern University, to build on prior studies from the Klein lab and others that indicated close links between Alzheimer’s disease and diabetes. Working with Claudine Bitel and Rajesh Kaswala, students at UMDNJ, the researchers tested whether untreated diabetes would provide a physiological model of Alzheimer neuropathology.

“The results were striking,” Frederikse said. “Because we used diabetes as an instigator of the disease, our study shows – for the first time directly – the link between Alzheimer’s and diabetes.”

The researchers found substantial increases in amyloid beta peptide pathology – a hallmark of Alzheimer’s disease – in the brain cortex and hippocampus concurrent with diabetes. They also found significant amyloid beta pathology in the retina and by contrast, when diabetes is not present, no observable pathology was detected in either the brain or the retina.

“Second, our study examined the retina, which is considered an extension of the brain, and is more accessible for diagnostic exams,” Frederikse added. “Our findings indicate that scientists may be able to follow the onset and progression of Alzheimer’s disease through retinal examination, which could provide a long sought after early-warning sign of the disease.”

This experimental model replicated spontaneous formation of amyloid beta “oligomer” assemblies in brain and retina which may help to explain one of the most widely recognized symptoms of Alzheimer’s. “This is exciting,” Klein said. “Oligomers are the neurotoxins now regarded as causing Alzheimer’s disease memory loss. What could cause them to appear and buildup in late-onset Alzheimer’s disease has been a mystery, so these new findings with diabetes represent an important step.”

Previous research indicated that insulin plays an important role in the formation of memories. Once attached to neurons, oligomers cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. This launches a vicious cycle in which diabetes induces oligomer accumulation which makes neurons even more insulin resistant.

“In light of the near epidemic increases in Alzheimer’s disease and diabetes today, developing a physiological model of Alzheimer neuropathology has been an important goal,” Kasinathan added. “It allows us to identify a potential biomarker for Alzheimer’s disease and may also make important contributions to Alzheimer drug testing and development.”

The current research was supported by a grant from the National Eye Institute of the National Institutes of Health, the National Institute of Aging, and the Neuroscience Research and Education Foundation. Drs. Kasinathan and Frederikse have applied for patent protection regarding this novel experimental model of Alzheimer neuropathology.

Provided by University of Medicine and Dentistry of New Jersey

Alzheimer's drug shows promise in early trial

Experimental agent similar to medicines already used to ease symptoms, but more study needed.

19  july 2012--Researchers say an investigational drug helped improve memory, language, attention and other mental skills in people with early Alzheimer's disease.

The study was funded by EnVivo Pharmaceuticals, which is developing the drug, dubbed EVP-6124. The results are to be presented Wednesday at the annual meeting of the Alzheimer's Association in Vancouver.

The study involved 409 patients with mild to moderate Alzheimer's disease who were either being treated with the drugs donepezil (Aricept) or rivastigmine (Exelon) or were receiving no treatment.

During the six-month, phase 2 trial, patients took either a placebo or one of three different doses of EVP-6124.

After 23 weeks of treatment, the patients in the high-dose group showed statistically significant benefits on tests of mental function compared to those taking the dummy pill. Some patients in the medium- and high-dose groups did experience mild to moderate gastrointestinal side effects, the team added.

"In our study, EVP-6124 provided significant benefits for people with mild to moderate Alzheimer's whether they were on currently approved therapy or not," Dr. Dana Hilt, senior vice president of clinical development and chief medical officer of EnVivo, said in an Alzheimer's Association news release.

The authors explain that EVP-6124 belongs to a family of drugs called alpha-7 nicotinic agonists, which amplify the effects of acetylcholine, a brain chemical that's essential for normal brain and memory function. People with Alzheimer's disease have greatly reduced levels of acetylcholine.

Currently, there are no effective treatments to fight Alzheimer's disease, although certain drugs may temporarily ameliorate symptoms.

For that reason, the new study "is potentially interesting, as there is a need for better symptomatic treatment of Alzheimer's disease," said Peter Davies, director of the Litwin Zucker Research Center for the Study of Alzheimer's Disease at the Feinstein Institute for Medical Research in New Hyde Park, N.Y.

He pointed out that the mechanism behind the new drug is not altogether novel. "Treating the deficiency of acetylcholine is the basis for the already approved drugs Aricept, Exelon and Razodyne," Davies said. "This drug does the same thing, but in a different way. The other drugs act to reduce the breakdown of acetylcholine: this drug mimics the effect of acetylcholine at one of the receptors for this compound."

He said that there are hints that this approach might do more than just ease symptoms, and might attack the underlying illness. But that remains speculative and "further studies do seem to be warranted," Davies said.

Another expert agreed.

"These promising effects are 'symptomatic' (the drug does not slow progression of disease), and the study is relatively small in size," noted Stephen Ferris, director of the Alzheimer's Disease Center and the clinical trials program at NYU Langone Medical Center's Comprehensive Center on Brain Aging in New York City.

Like Davies, Ferris stressed that "if the results can be confirmed in a larger trial, the drug would be an important addition to current Alzheimer treatments."

Findings presented at medical meeting are typically considered preliminary until published in a peer-reviewed journal.

New York Stem Cell Foundation scientists featured for new model of Alzheimer's disease

A team of scientists at The New York Stem Cell Foundation (NYSCF) Laboratory led by Scott Noggle, PhD, NYSCF–Charles Evans Senior Research Fellow for Alzheimer's Disease, has developed the first cell-based model of Alzheimer's disease (AD) by reprogramming skin cells of Alzheimer's patients to become brain cells that are affected in Alzheimer's. This will allow researchers to work directly on living brain cells suffering from Alzheimer's, which until now had not been possible.

18 july 2012--Andrew Sproul, PhD, a postdoctoral associate in Dr. Noggle's laboratory, will present this work on Thursday, July 19 at the Alzheimer's Association International Conference (AAIC) held in Vancouver.

Dr. Noggle and his team reprogrammed skin cell samples taken from twelve patients diagnosed with early-onset Alzheimer's and from healthy, genetically related individuals into induced pluripotent stem (iPS) cells, which can differentiate into any cell type. The team of scientists used these iPS cells to create cholinergic basal forebrain neurons, the brain cells that are affected in Alzheimer's. These cells recapitulate the features and cellular-level functions of patients suffering from Alzheimer's, a devastating disease that affects millions of people globally but for which there is currently no effective treatment.

NYSCF has pioneered the creation of disease models based on the derivation of human cells. Four years ago, a NYSCF-funded team created a cell-based model for ALS, or motor neuron disease, the first patient-specific stem cells created for any disease. The cell-based model for Alzheimer's builds on this earlier work.

"Patient derived AD cells will prove invaluable for future research advances, as they already have with patient-derived ALS cells," said NYSCF CEO Susan Solomon. "They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells. Although research on animals has provided valuable insight into AD, we aren't mice, and animals don't properly reflect the features of the disease we are trying to cure. As we work to find new drugs and treatments our research should focus on actual human sufferers of Alzheimer's disease," emphasized Ms. Solomon

This cell-based model has already led to important findings. Preliminary results of this NYSCF research, done in collaboration with Sam Gandy, MD, PhD, an international expert in the pathology of Alzheimer's at Mount Sinai School of Medicine, demonstrated differences in cellular function in Alzheimer's patients. Specifically, Alzheimer's neurons produce more of the toxic form of beta amyloid, the protein fragment that makes up amyloid plaques, than in disease-free neurons.

"iPS cell technology, along with whole genome sequencing, provide our best chance at unravelling the causes of common forms of Alzheimer's disease," noted Dr. Gandy.

"This collaboration is a great example of how NYSCF is bringing together experts in stem cell technology and clinicians to save and enhance lives by finding better treatments," Ms. Solomon explained.

The research to be reported at the AAIC by Andrew Sproul focused on stem cell models of individuals with presenilin-1 (PSEN1) mutations, a genetic cause of AD. As Dr. Sproul has said, this cell-based model could "revolutionize how we discover drugs to potentially cure Alzheimer's disease."

Provided by New York Stem Cell Foundation

Open access journals reaching the same scientific impact as subscription journals

BioMed Central's open access journal BMC Medicine adds scientific rigour to the debate about open access research, by publishing an article which compares the scientific impact of open access with traditional subscription publishing and has found that both of these publishing business models produce high quality peer reviewed articles.

17 july 2012--The debate about who should pay for scientific publishing is of continuing importance to the scientific community but also to the general public who not only often pay for the research though charitable contributions, their taxes, and by buying products, but are also affected by the results contained within these articles.

Many publically funded agencies, such as the Wellcome Trust and NIH require that scientific research sponsored by them is made freely available to the public. However the issues aren't as simple as just putting the results of your research on line. Scientific research goes through the quality control filter of peer review and journals act as gatekeepers performing quality-assuring peer review, and who provide web-based repositories. Scientists currently rely on publishing in peer reviewed high quality journals to show that their research itself is of good quality, is of importance to their field of research, and consequently improves their chances of obtaining funding to continue their work.

One way of measuring quality is by impact factors calculated from citation data (how many times other scientists have mentioned the research). Bo-Christer Björk from Hanken School of Economics, Helsinki, and David Solomon from Michigan State University compared the impact factors of 610 open access journals and over 7000 subscription journals.

The citation rate for subscription journals was overall 30% higher than for open access ones but this difference was largely due to a high share of older OA journals, particularly from regions like Latin America in the citation indexes. When like was compared with like, for instance, journals founded after 2000 from difference regions or disciplines, the differences disappeared.

Bo-Christer Björk, explained, The open access debate has included accusations from some traditional publishers and their lobbyists that Open Access publishing implies low scientific quality and endangers the quality assurance function of the peer review system that the academic community and publishers have built up over decades."

Explaining the results Prof Björk said, "If you take into account the journal discipline, location of publisher and age of publication the differences in impact between open access and subscription journals largely disappear. In medicine and health, open access journals founded in the last 10 years are receiving on average as many citations as subscription journals launched during the same time."

David Solomon continued, "It is easy to see why scientists might be sceptical of electronic, open access journals – after all they have their reputation to maintain. Open access journals that fund publishing with article processing charges (APCs), sometimes called gold open access, are on average cited more than other OA journals. Since the launch of professionally run high quality biomedical journals in 2000 gold OA has increased by 30% per year and many of these are on a par with their subscription counterparts."

More information: Open access versus subscription journals: a comparison of scientific impact Bo-Christer Björk and David Solomon BMC Medicine (in press)

Provided by BioMed Central

Mayo Clinic maps brain, finds Alzheimer's patients drive differently

Activity lingers longer in certain areas of the brain in those with Alzheimer's than it does in healthy people, Mayo Clinic researchers who created a map of the brain found. The results suggest varying brain activity may reduce the risk of Alzheimer's disease. The study, "Non-stationarity in the "Resting Brain's" Modular Architecture," was presented at the Alzheimer's Association International Conference and recently published in the journal PLoS One.

16 july 2012--Researchers compared brain activity to a complex network, with multiple objects sharing information along pathways.

"Our understanding of those objects and pathways is limited," says lead author David T. Jones, M.D. "There are regions in the brain that correspond to those objects, and we are not really clear exactly what those are. We need a good mapping or atlas of those regions that make up the network in the brain, which is part of what we were doing in this study."

Researchers examined 892 cognitively normal people taking part in the Mayo Clinic Study of Aging, and set out to create an active map of their brains while the people were "at rest," not engaged in a specific task. To do this, they employed task-free, functional magnetic resonance imaging to construct an atlas of 68 functional regions of the brain, which correspond to the cities on the road map.

Researchers filled in the roads between these regions by creating dynamic graphic representations of brain connectivity within a sliding time window.

This analysis revealed that there were many roads that could be used to exchange information in the brain, and the brain uses different roads at different times. The question to answer then, said Dr. Jones, is whether or not Alzheimer's patients used this map and these roads in a different way than their healthy peers.

"What we found in this study was that Alzheimer's patients tended to spend more time using some roads and less time using other roads, biasing one over the other," he says.

While more research is needed, the researchers say one implication is that how we use our brains may protect us from Alzheimer's. Dr. Jones says exercise, education, and social contacts may help balance activity in the brain.

"Diversifying the mental space that you explore may actually decrease your risk for Alzheimer's," he says.

Provided by Mayo Clinic

Cranberry products associated with prevention of urinary tract infections

Use of cranberry-containing products appears to be associated with prevention of urinary tract infections in some individuals, according to a study that reviewed the available medical literature and was published by Archives of Internal Medicine.

15 july 2012--Urinary tract infections (UTIs) are common bacterial infections and adult women are particularly susceptible. Cranberry-containing products have long been used as a "folk remedy" to prevent the condition, according to the study background.

Chih-Hung Wang, M.D., of National Taiwan University Hospital and National Taiwan University College of Medicine, and colleagues reviewed the available medical literature to reevaluate cranberry-containing products for the prevention of UTI.

"Cranberry-containing products tend to be more effective in women with recurrent UTIs, female populations, children, cranberry juice drinkers, and people using cranberry-containing products more than twice daily," the authors note.

The authors identified 13 trials, including 1,616 individuals, for qualitative analysis and 10 of these trials, including 1,494 individuals, were included in quantitative analysis. The random-effects pooled risk ratio for cranberry users vs. nonusers was 0.62, according to the study results.

"In conclusion, the results of the present meta-analysis support that consumption of cranberry-containing products may protect against UTIs in certain populations. However, because of the substantial heterogeneity across trials, this conclusion should be interpreted with great caution," the authors conclude.

More information: Arch Intern Med. 2012;172[13]:988-996.

Provided by JAMA and Archives Journals

'Natural' protection against Alzheimer’s disease

deCODE Genetics, together with their colleagues from the pharmaceutical company Genentech, reported today in the journal Nature the discovery of a variant of the amyloid precursor protein (APP) gene that confers protection against both Alzheimer's disease (AD) and cognitive decline in the elderly. The findings also indicate a linkage between age-related cognitive decline and late-onset forms of AD, the most common cause of dementia.

14 july 2012--"Our results suggest that late-onset Alzheimer's disease may represent the extreme of more general age-related decline in cognitive function," said study lead author Kari Stefansson, M.D., Dr. Med., CEO of deCODE Genetics. "Also important, these data support certain Alzheimer's disease drug development programs--some of which are already in human clinical trials."

Alzheimer's disease is a progressive neurodegenerative disease associated with the production and accumulation of beta-amyloid peptides produced by cleaving bits off the APP. While several mutant forms of the APP gene have been linked to early-onset, aggressive forms of AD, there is limited evidence supporting a role for mutations in the gene in the more common late-onset form of the disease.

In searching for low-frequency variants of the APP gene associated with AD, deCODE scientists found a significant association with a mutation in whole genome sequence data from 1,795 Icelanders. The research team showed that the mutation is significantly more common in the study's elderly control group than in those with AD, suggesting that the mutation confers protection against the disease.

The Genentech team then tested these findings using in vitro cellular assays with wild-type APP and APP enriched with A673T, the mutation allele. Importantly, they showed a significantly reduced production of amyloid beta in cells with A673T.

"Our genetic data indicate that the mutation is protective against Alzheimer's disease," said Stefansson. "Our findings and the in vitro work done by Genentech also provide a proof of principle for the idea that blocking BACE1 cleavage of APP may protect against Alzheimer's, offering greater confidence to pharmaceutical companies with active BACE1 inhibitor drug development programs."

To study the association of the protective mutation with general cognitive decline, the research team examined the frequency of the mutation in the original Icelandic control group of those cognitively intact at age 85. The team found an enrichment of the mutation in this group, consistent with its protective effect against AD.

Extending this work further, the team investigated cognitive function using a seven-category test in carriers of the mutation and non-carriers in the age range of 80 to 100 years old. The research team found a statistically significant difference between carriers and non-carriers, with the carriers of the mutation having a score indicative of better-conserved cognition. After removing known AD cases, the team again found that carriers had better cognitive function, suggesting that the mutation extends its protective effect to the elderly in general.

"The implication of these data is that general cognitive decline and late-onset Alzheimer's disease share biological pathways," said Stefansson. "It also suggests that approaches to treating Alzheimer's may have benefit to those elderly who do not carry the protective mutation, and do not suffer from AD."

Alzheimer's disease, a progressive neurodegenerative disorder, is the most common form of dementia that affects four to eight percent of the elderly population worldwide. The neuropathological features of AD are the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles in the hippocampus and cortical grey matter of the AD brain.

Age-specific prevalence of AD nearly doubles after age 65, leading to a prevalence of greater than 25 percent in those over the age of 90.

More information: DOI: 10.1038/nature11283

Alzheimer's plaques in PET brain scans identify future cognitive decline

12 july 2012--Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer's disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer's disease.

"Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function," said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . "Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect."

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer's disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer's dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer's disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial's start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial's start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer's dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

"For the most part we have been blind about who would progress and who wouldn't, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment," Doraiswamy said.

He said the study's results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer's Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer's by itself.

Provided by Duke University Medical Center

Study examines quality of life factors at end of life for patients with cancer

Better quality of life at the end of life for patients with advanced cancer was associated with avoiding hospitalizations and the intensive care unit, worrying less, praying or meditating, being visited by a pastor in a hospital or clinic, and having a therapeutic alliance with their physician, according to a report published Online First by Archives of Internal Medicine.

11 july 2012--When treatments to cure a patient's cancer are no longer an option, the focus of care often shifts from prolonging life to promoting the quality of life (QOL) at the end of life (EOL). But researchers note in their study background that there has been a gap in data on the strongest predictors of higher QOL at the EOL.

"The aim of this study was to identify the best set of predictors of QOL of patients in their final week of life. By doing so, we identify promising targets for health care interventions to improve QOL of dying patients," the authors note.

The study by Baohui Zhang, M.S., formerly of the Dana-Farber Cancer Institute, Boston, and colleagues included 396 patients with advanced cancer and their caregivers as part of the Coping with Cancer study. The average age of patients was almost 59 years.

A set of nine factors explained the most variance in patients' QOL at the EOL: intensive care stays in the final week, hospital deaths, patient worry at baseline, religious prayer or meditation at baseline, site of cancer care, feeding tube use in the final week, pastoral care within the hospital or clinic, chemotherapy in the final week, and a patient-physician therapeutic alliance where the patient felt they were treated as a "whole person," according to the study.

"Two of the most important determinants of poor patient quality QOL at the EOL were dying in a hospital and ICU stays in the last week of life. Therefore, attempts to avoid costly hospitalizations and to encourage transfer of hospitalized patients to home or hospice might improve patient QOL at the EOL," the authors comment.

Patient worry at baseline also was "one of the most influential predictors of worse QOL at the EOL," the authors note.

"By reducing patient worry, encouraging contemplation, integrating pastoral care within medical care, fostering a therapeutic alliance between patient and physician that enables patients to feel dignified, and preventing unnecessary hospitalizations and receipt of life-prolonging care, physicians can enable their patients to live their last days with the highest possible level of comfort and care," the authors conclude.

In an invited commentary, Alan B. Zonderman, Ph.D., and Michele K. Evans, M.D., of the Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Md., write: "The concept of quality of the EOL [end of life] in cancer patients has been under examined in cancer medicine in the quest to develop newer, more advanced, and effective modalities of interventional cytotoxic therapies. This study highlights the scarcity of research in an area that can give us important tools in further refining coherent treatment strategies for patients throughout the timeline of cancer treatment and disease trajectory."

"It is surprising at this stage in the development and implementation of complex multimodal cancer treatment strategies that the factors most critical in influencing the quality of the EOL are not clearly defined and considered along the entire timeline beginning with cancer diagnosis," they continue.

"This work, as well as the American Society of Clinical Oncology statement, support early introduction of palliative care for advanced cancer patients," the authors conclude.

More information: Arch Intern Med. Published online July 9, 2012. doi:10.1001/archinternmed.2012.2364 
Arch Intern Med. Published online July 9, 2012. doi:10.1001/archinternmed.2012.3169

Provided by JAMA and Archives Journals

15 top medical organizations agree on hormone therapy use

After 10 years of debate regarding the risks and benefits of hormone therapy, 15 top medical organizations have come together to issue a statement of agreement regarding the benefits of hormone therapy for symptomatic menopausal women. It was July 9, 2002, when the controversial, highly publicized Women's Health Initiative (WHI) published its assessment of hormone therapy for the prevention of chronic disease and concluded that risks exceeded benefits. The new joint statement, prepared by The North American Menopause Society (NAMS), the American Society for Reproductive Medicine (ASRM), and The Endocrine Society, concludes that hormone therapy is still an acceptable treatment for menopausal symptoms. This statement has been endorsed by 12 other leading organizations in women's health.

10 july 2012--The purpose of this statement is to reassure women and their providers that hormone therapy is acceptable and relatively safe for healthy, symptomatic, recently postmenopausal women. Over the last 10 years, there has been a complete abandonment of hormone therapy in some settings accompanied by reluctance to treat women who would benefit from relief of their symptoms. As a result, some women have sought unproven alternative therapies.

"We believe that too many symptomatic women are missing out on the proven benefits of hormone therapy because the results of the WHI, which studied the long-term use of hormones to prevent chronic disease, were misinterpreted for women with menopausal symptoms" said Dr. Margery Gass, Executive Director for NAMS. "Women and clinicians are frustrated by the many conflicting recommendations. That's why we initiated this effort to bring these notable medical organizations together in agreement regarding the use of hormone therapy."

Roger Lobo, MD, Past President of the American Society for Reproductive Medicine added, "Physicians can help patients determine, based on their own particular characteristics and history, whether or not they are good candidates for hormone therapy and what type of HT will provide them the greatest relief at the lowest risk. A decade of research and analysis has shown us that the generalized conclusions of the WHI do not apply to younger women at the beginning of the menopausal transition."

"The results of the WHI and the conflicting reports that followed led many women to believe hormone therapy may not be a safe treatment for menopausal symptoms," said Janet E. Hall, MD, immediate Past President of The Endocrine Society. "We want women to know that there are options out there for relief of their menopausal symptoms. The level of risk depends on the individual, her health history, age, and the number of years since her menopause began."

When it comes to the safety and effectiveness of hormone therapy, one commonly heard lament is, "Even the experts don't agree." This statement was prepared to address this misperception by presenting evidence-based key concepts about hormone therapy to assist women and their clinicians in making informed decisions about use of hormone therapy when appropriate.

Major points of agreement among the societies include: 

• Hormone therapy is an acceptable option for the relatively young (up to age 59 or within 10 years of menopause) and healthy women who are bothered by moderate to severe menopausal symptoms. Individualization is key in the decision to use hormone therapy.
• If women have only vaginal dryness or discomfort with intercourse, the preferred treatments are low doses of vaginal estrogen.
• Women who still have a uterus need to take a progestogen (progesterone or a similar product) along with the estrogen to prevent cancer of the uterus. Women who have had their uterus removed can take estrogen alone.
• Both estrogen therapy and estrogen with progestogen therapy increase the risk of blood clots in the legs and lungs, similar to birth control pills, patches, and rings. Although the risks of blood clots and stroke increase with either type of hormone therapy, the risk is rare in women ages 50-59.
• An increased risk in breast cancer is seen with 5 or more years of continuous estrogen with progestogen therapy, possibly earlier. The risk decreases after hormone therapy is stopped.

Provided by The North American Menopause Society (NAMS)

Patients trust doctors but consult the Internet

Patients look up their illnesses online to become better informed and prepared to play an active role in their care  not because they mistrust their doctors, a new University of California, Davis, study suggests.

09 july 2012--The study surveyed more than 500 people who were members of online support groups and had scheduled appointments with a physician.

"We found that mistrust was not a significant predictor of people going online for health information prior to their visit," said Xinyi Hu, who co-authored the study as part of her master's thesis in communication. "This was somewhat surprising and suggests that doctors need not be defensive when their patients come to their appointments armed with information taken from the Internet."

With faculty co-authors at UC Davis and the University of Southern California, Hu examined how the study subjects made use of support groups, other Internet resources, and offline sources of information, including traditional media and social relations, before their medical appointments.

The study found no evidence that the users of online health information had less trust in their doctors than patients who did not seek information through the Internet.

"The Internet has become a mainstream source of information about health and other issues," Hu noted. "Many people go online to get information when they anticipate a challenge in their life. It makes sense that they would do the same when dealing with a health issue."

Although physician mistrust did not predict reliance on the Internet prior to patients' medical visits, several other factors did. For example, people were more likely to seek information online when their health situation was distressful or when they felt they had some level of personal control over their illness. Online information-seeking was also higher among patients who believed that their medical condition was likely to persist.

The study also found that Internet health information did not replace more traditional sources of information. Instead, patients used the Internet to supplement offline sources, such as friends, health news reports and reference books.

"With the growth of online support groups, physicians need to be aware that many of their patients will be joining and interacting with these groups. These patients tend to be very active health-information seekers, making use of both traditional and new media," the study said.

Almost 70 percent of the study subjects reported they were planning to ask their doctor questions about the information they found, and about 40 percent said they had printed out information to take with them to discuss with their doctors. More than 50 percent of subjects said they intended to make at least one request of their doctor on the basis of Internet information.

"As a practicing physician, these results provide some degree of reassurance," said co-author Richard L. Kravitz, a UC Davis Health System professor of internal medicine and study co-author. "The results mean that patients are not turning to the Internet out of mistrust; more likely, Internet users are curious information seekers who are just trying to learn as much as they can before their visit."

Online support groups provide online virtual meeting places for sharing information and social support. In February 2011, there were more than 12,000 groups listed in the support category of Yahoo! Groups Health and Wellness directory. Even so, other studies suggest that only 9 percent of Americans and 37 percent of patients with chronic disease have participated in online support groups. The majority of subjects assessed their own health as fair or poor.

More information: The study, "The Prepared Patient: Information Seeking of Online Support Group Members Before Their Medical Appointments" was published earlier this year in the Journal of Health Communication.

Provided by UC Davis

Half of heart patients make mistakes with their meds: study

Almost 23 percent of errors were deemed serious, researchers report.

08 july 2012-- Half of patients hospitalized for a heart attack or heart failure will make a mistake with their medications within a month of checking out of the hospital, new research shows.

These mistakes were as common among people who received counseling and guidance from a pharmacist as those who did not.

In the study, 50 percent of 851 participants had one or more medication error. Of these, about 23 percent were deemed to be serious and 1.8 percent were considered life-threatening. The findings appear in the July 3 issue of the Annals of Internal Medicine.

The study took place at Vanderbilt University Hospital in Nashville, Tenn., and Brigham and Women's Hospital in Boston. The patients tended to be highly educated, and yet they still had problems following instructions.

"This shows how vulnerable patients are in the transition from hospital to home," said Dr. Gregg Fonarow, a spokesman for the American Heart Association and a professor of cardiovascular medicine at the University of California, Los Angeles. "Many had thought that having pharmacist assistance, counseling and individual follow-up would reduce or even eliminate the likelihood of having an adverse drug event," he noted.

"Patients, caregivers and family members need to be knowledgeable about drug names, dosing and which medications should be discontinued, and which should continued, after hospitalization," Fonarow said. "This information should be given verbally and in writing to all involved parties. It needs to be recognized that even with all of these steps, there is still a potential for clinically important medical errors."

Dr. Adam Auerbach, director of inpatient cardiac services at North Shore University Hospital in Manhasset, N.Y., said that medication errors continue to be a big problem.

He noted that his hospital is in the process of starting some pilot programs to curb medication errors.

"We are looking at a 'teach-back' program where we each teach patients about their medications and then they teach it back to us," he said. "We are also rolling out a program where we go to a patient's house within 72 hours after discharge to make sure they are on the right medications."

According to Auerbach, there is definitely an economic aspect to the problem. Some people may skip doses or split pills to cut costs. Choosing generic medications, when possible, can help eliminate the cost factor.

Individuals with strong social support systems tend to do better as they have one or more caregivers looking over their shoulder. "There is a huge population who, for various reasons, don't fully understand their instructions and who don't have a support network, and those are the people we are trying to reach," he said, adding that he often asks patients to bring all their medications with them to follow-up appointments to make sure they are being taken correctly.

Allen Vaida, executive vice president of the Institute for Safe Medication Practices, in Horsham, Pa., said that "it is amazing that the numbers were that high at two institutions that have good systems in place. One way to reduce rates of medication errors and adverse drug events is to use only one pharmacy for all your prescription and medication needs. This way, any interactions or potential problems are more likely to get flagged. There are a handful of drugs that are more likely to cause problems, including blood thinners. Focusing our efforts on some of the drugs that we know may cause issues can also be helpful."

Diabetes drug metformin makes brain cells grow

The widely used diabetes drug metformin comes with a rather unexpected and alluring side effect: it encourages the growth of new neurons in the brain. The study reported in the July 6th issue of Cell Stem Cell also finds that those neural effects of the drug also make mice smarter.

07 july 2012--The discovery is an important step toward therapies that aim to repair the brain not by introducing new stem cells but rather by spurring those that are already present into action, says the study's lead author Freda Miller of the University of Toronto-affiliated Hospital for Sick Children. The fact that it's a drug that is so widely used and so safe makes the news all that much better.

Earlier work by Miller's team highlighted a pathway known as aPKC-CBP for its essential role in telling neural stem cells where and when to differentiate into mature neurons. As it happened, others had found before them that the same pathway is important for the metabolic effects of the drug metformin, but in liver cells.

"We put two and two together," Miller says. If metformin activates the CBP pathway in the liver, they thought, maybe it could also do that in neural stem cells of the brain to encourage brain repair.

The new evidence lends support to that promising idea in both mouse brains and human cells. Mice taking metformin not only showed an increase in the birth of new neurons, but they were also better able to learn the location of a hidden platform in a standard maze test of spatial learning.

While it remains to be seen whether the very popular diabetes drug might already be serving as a brain booster for those who are now taking it, there are already some early hints that it may have cognitive benefits for people with Alzheimer's disease. It had been thought those improvements were the result of better diabetes control, Miller says, but it now appears that metformin may improve Alzheimer's symptoms by enhancing brain repair.

Miller says they now hope to test whether metformin might help repair the brains of those who have suffered brain injury due to trauma or radiation therapies for cancer.

More information: Wang et al.: "Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation." Cell Stem Cell, DOI:10.1016/j.stem.2012.03.016

Abstract 
Although endogenous recruitment of adult neural stem cells has been proposed as a therapeutic strategy, clinical approaches for achieving this are lacking. Here, we show that metformin, a widely used drug, promotes neurogenesis and enhances spatial memory formation. Specifically, we show that an atypical PKC-CBP pathway is essential for the normal genesis of neurons from neural precursors and that metformin activates this pathway to promote rodent and human neurogenesis in culture. Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent fashion, and in so doing enhances spatial reversal learning in the water maze. Thus, metformin, by activating an aPKC-CBP pathway, recruits neural stem cells and enhances neural function, thereby providing a candidate pharmacological approach for nervous system therapy.

Provided by Cell Press

Higher doses of vitamin D prevent fractures in older women

But evidence review found less than 800 IUs a day didn't seem to make a difference.

06 july 2012-- In the latest study to look at the effect of vitamin D on fracture risk, Swiss researchers found that taking more than 800 international units (IU) of vitamin D daily could reduce the risk of hip fractures in older women by 30 percent.

"Vitamin D supplementation is effective in fracture reduction, including hip fractures," said study author Dr. Heike Bischoff-Ferrari, from the Center on Aging and Mobility at the University of Zurich and Wald City Hospital, also in Zurich.

"However, dose matters, as we saw this benefit only at the highest intake level of greater than 800 IU per day, and no dose below 792 IU per day reduced fracture risk," she said.

If everyone took more than 800 IU of vitamin D daily, the impact on public health could be enormous because hip fractures are the most severe and frequent fractures among the elderly, according to Bischoff-Ferrari.

Results of the study are published in the July 5 issue of the New England Journal of Medicine.

Vitamin D is important for bone health, according to Dr. Anna Lasak, clinical director of the department of rehabilitation and the women's physical medicine and rehabilitation program at Montefiore Medical Center, in New York City. The body makes vitamin D when exposed to sunlight. Sunscreen blocks this effect.

Vitamin D is also found in fatty fish, eggs and some mushrooms, she said. It's also added to dairy products, some cereals and some breads, according to Lasak. But, she said, it can be difficult, especially for elderly people, to get enough vitamin D from these sources. In addition, elderly people may have digestive issues that can cause their bodies to absorb even less vitamin D.

A number of studies have been done looking at vitamin D and bone health, and the studies have often come up with conflicting findings, with some showing benefits, while others found no benefits. In mid-June, the U.S. Preventive ServicesTask Force recommended that postmenopausal women should not take low-dose vitamin D supplements (400 IU) because there was no evidence of benefit. The task force, however, said there wasn't yet enough clear evidence on higher doses of vitamin D to make a recommendation one way or the other.

The current study is a pooled analysis of 11 double-blind, randomized controlled trials of vitamin D supplementation with or without calcium compared to a placebo or calcium supplementation alone.

The studies included more than 31,000 people. All of the participants in the studies were over 65, with an average age of 76. Most (91 percent) of the volunteers in the studies were women.

They found that people taking less than 800 IU daily showed no statistically significant drop in fracture risk. However, those taking over 800 IU reduced the risk of hip fracture by 30 percent and the risk of non spine-related fractures by 14 percent, according to the study.

"Our data strongly support a daily vitamin D supplement of 800 IU per day in adults age 65 and older to lower their risk of fracture, including those living at home and those living in nursing homes, including men and women, and the younger and the old," Bischoff-Ferrari said.

Lasak said 800 IU is a safe level of vitamin D intake for just about anyone. But, she said, it's better for older folks to have their vitamin D levels measured first. Some may not need additional vitamin D, but many actually need more than 800 IU a day.

"Most people do have a deficiency," she said. While 800 IU is a safe limit, that may not be enough, she said. No one should exceed levels of 4,000 IU, Lasak added. That's the upper safe limit of this nutrient.

She said it's also important to ensure that you're getting enough calcium. The recommendation is for between 1,000 and 1,200 milligrams (mg) a day, with older people needing more, she said. Lasak recommended getting the bulk of your calcium from foods, rather than a supplement, because some studies have suggested possible harm from higher levels of calcium intake from supplements.

Bischoff-Ferrari said the current analysis also suggested that higher levels of calcium supplementation (more than 1,000 mg) may reduce vitamin D's benefit.

Revolutionary project will obtain entire genome sequences in fight against Alzheimer's

Since 2004, UCLA's Laboratory of Neuro Imaging (LONI) has been responsible for receiving, organizing, archiving and disseminating the stream of data generated by the Alzheimer's Disease Neuroimaging Initiative (ADNI), an ambitious, worldwide effort by scientists to define the progression of Alzheimer's disease.

05 july 2012--That stream of data will now turn into a flood, as LONI partners with an ambitious public–private effort to dig deeper into the causes of this devastating disease by obtaining the whole-genome sequencing of the more than 800 people enrolled in ADNI — the largest cohort of individuals related to a single disease.

This work is expected to generate at least 165 terabytes of new genetic data, an amount roughly equivalent to the information contained in 165,000 entire copies of the Encyclopedia Britannica.

"This effort, involving almost 60 sites around the country, is the best chance we have for understanding this brutal disease," said LONI director Arthur Toga, a UCLA professor of neurology and one of the collaborators on the management of the sequencing efforts. "We collect vast amounts of imaging, cognitive and biosample data from hundreds of subjects with Alzheimer's disease, those at risk, and controls. One of the more unique aspects of this study is that all data are shared with any scientist, without embargo. We have already engaged many scientists around the world with this open access."

The new genome project is a significant extension of ADNI, which now enrolls people with Alzheimer's disease, mild cognitive impairment and normal cognition who have agreed to be studied in great detail over time. The goal is to identify and understand markers of the disease with the hope of improving early diagnosis and accelerating the discovery of new treatments.

All of the ADNI data continues to flow into UCLA's LONI, including detailed, long-term assessments of neuropsychological measures, standardized structural and functional imaging, and precise biomarker measures from blood and spinal fluid. Now, added to this wealth of information will be the ADNI participants' entire genome sequences, which determine all 6 billion letters in an individual's DNA in one comprehensive analysis.

Once the sequences are completed — approximately 16 weeks after the sequencing project starts — the raw data will rapidly be made available to qualified scientists around the globe to mine for novel targets for risk-assessment, new therapies and much-needed insights into the causes of Alzheimer's.

All of the information from ADNI has always been made freely available, without delay, to scientists; to date, this has resulted in more than 500 scientific manuscripts.

ADNI is a public–private research project led by the National Institutes of Health with private sector support through the Foundation for NIH. Launched in 2004, ADNI's public–private funding consortium includes pharmaceutical companies, science-related businesses and nonprofit organizations, including the Alzheimer's Association and the Northern California Institute for Research and Education.

The ADNI whole-genome sequencing is being funded through a partnership between the Alzheimer's Association and the nonprofit Brin Wojcicki Foundation, a charitable organization created by Anne Wojcicki, founder of the online genetics firm 23andMe, and her husband, Sergey Brin, co-founder of Google.

"Sequencing the ADNI participants and making the genetic data immediately available to researchers around the world will significantly improve our understanding and approach to Alzheimer's disease," Anne Wojcicki said. "The ADNI team and the Alzheimer's Association are impressive in their ability to quickly make decisions that are truly in the best interest of people with Alzheimer's."

"Linking these deep-sequencing data with imaging and other data may help solve the puzzles in Alzheimer's that still vex us," Toga said. "Certainly, a more complete picture will emerge, hopefully leading to effective therapies."

Provided by University of California, Los Angeles

Brazil has laws that protect against "Big Food" and "Big Snack"

Under pressure from civil society organizations, the Brazilian government has introduced legislation to protect and improve its traditional food system, standing in contrast to the governments of many industrialized countries that have partly surrendered their prime duty to protect public health to transnational food companies, argue nutrition and public health experts writing in this week's PLoS Medicine.

04 july 2012--Carlos Monteiro and Geoffrey Cannon, from the Center for Epidemiological Studies in Health and Nutrition of the University of São Paulo, explain that, in Brazil, traditional long-established food systems and dietary patterns are being displaced by ultra-processed products made by transnational food corporations ("Big Food" and "Big Snack") contributing to increases in the incidence of obesity and of major chronic diseases, and adversely affecting public health and public goods by undermining culture, meals, the family, community life, local economies, and national identity.

The authors argue: "The use of law to protect and improve food systems and supplies, and thus public health, may be difficult in parts of the world where governments have already ceded the responsibility of governance to transnational and other corporations. However, in Brazil protection of public health still remains a prime duty of government ."

The authors explain that by law, all Brazilian children attending state schools are entitled to one daily meal at school, at least 70% of the food supplied to schools must be fresh or minimally processed, and a minimum of 30% of this food must be sourced from local family farmers. They say that such measures help to check the penetration of transnational corporations into Brazil.

Although the penetration of such corporations into Brazil has been rapid, the tradition of shared and family meals remains strong and is likely to provide protection to national and regional food systems.

The authors say: "Notwithstanding intense pressures, which include ubiquitous television and internet propaganda designed to turn eating and drinking into constant individual snacking, food and drink consumption is not yet dislocated and isolated from family and social life in Brazil."

The authors argue that Brazil's experiences in resisting "Big Food" and "Big Snack" can help other countries. They say: "the Brazilian experience provides a basis for the design of rational, comprehensive, and effective public health policies and actions designed to protect and promote nutrition in all its senses."

More information: Monteiro CA, Cannon G (2012) The Impact of Transnational ''Big Food'' Companies on the South: A View from Brazil. PLoS Med 9(7): e1001252.doi:10.1371/journal.pmed.1001252

Provided by Public Library of Science

Years before diagnosis, quality of life declines for Parkinson's disease patients

Growing evidence suggests that Parkinson's disease (PD) often starts with non-motor symptoms that precede diagnosis by several years. In the first study to examine patterns in the quality of life of Parkinson' disease patients prior to diagnosis, researchers have documented declines in physical and mental health, pain, and emotional health beginning several years before the onset of the disease and continuing thereafter. Their results are reported in the latest issue of Journal of Parkinson's Disease.

03 july 2012--"We observed a decline in physical function in PD patients relative to their healthy counterparts beginning three years prior to diagnosis in men and seven and a half years prior to diagnosis in women," says lead investigator Natalia Palacios, PhD, Department of Nutrition, Harvard School of Public Health. "The decline continues at a rate that is five to seven times faster than the average yearly decline caused by normal aging in individuals without the disease."

The study included 51,350 male health professionals enrolled in the Health Professionals Follow Up Study (HPFS) and 121,701 female registered nurses enrolled in the Nurses' Health Study (NHS). In both ongoing studies, participants fill out biannual questionnaires about a variety of lifestyle characteristics and document the occurrence of major chronic disease. In the NHS study, questionnaires measured health-related quality of life in eight areas: physical functioning, role limitations due to physical problems, role limitations due to emotional problems, vitality, bodily pain, social functioning, mental health, and general health perceptions. In the HPFS, only physical functioning was assessed.

Researchers identified 454 men and 414 women with PD in the two cohorts. At 7.5 years prior to diagnosis, physical function among PD cases, in both men and women, was comparable to that in the overall cohort. A decline began approximately 3 years prior to diagnosis in men and approximately 7.5 years prior to diagnosis in women. Physical function continued to decline thereafter at a rate of 1.43 and 2.35 points per year in men and women, respectively. In comparison, the average yearly decline in individuals without PD was 0.23 in men and 0.42 in women. Other measures of quality of life, available only in women, declined in a similar pattern.

Dr. Palacios notes that a strength of the study is the availability of prospective data on both PD patients and a healthy comparison group, and the ability to chart the deterioration in functioning and quality of life over the whole study follow-up, which included many years prior to diagnosis.

"This result provides support to the notion that the pathological process leading to PD may start several years before PD diagnosis," says Dr. Palacios. "Our hope is that, with future research, biological markers of the disease process may be recognizable in this preclinical phase."

Provided by IOS Press

Researchers identify role of FOXO1 gene in Parkinson's disease

A recent study led by researchers at Boston University School of Medicine (BUSM) revealed that the FOXO1 gene may play an important role in the pathological mechanisms of Parkinson's disease. These findings are published online in PLoS Genetics, a peer-reviewed open-access journal published by the Public Library of Science.

02 july 2012--The study was led by Alexandra Dumitriu, PhD, a postdoctoral associate in the department of neurology at BUSM. Richard Myers, PhD, professor of neurology at BUSM, is the study's senior author.

According to the Parkinson's Disease Foundation, 60,000 Americans are diagnosed with Parkinson's disease each year and approximately one million Americans are currently living with the disease.

Parkinson's disease is a complex neurodegenerative disorder characterized by a buildup of proteins in nerve cells that lead to their inability to communicate with one another, causing motor function issues, including tremors and slowness in movement, as well as dementia. The substantia nigra is an area of the midbrain that helps control movement, and previous research has shown that this area of the brain loses neurons as Parkinson's disease progresses.

The researchers analyzed gene expression differences in brain tissue between 27 samples with known Parkinson's disease and 26 samples from neurologically healthy controls. This data set represents the largest number of brain samples used in a whole-genome expression study of Parkinson's disease to date. The novel aspect of this study is represented by the researchers' emphasis on removing possible sources of variation by minimizing the differences among samples. They used only male brain tissue samples that showed no significant marks of Alzheimer's disease pathology, one of the frequently co-occurring neurological diseases in Parkinson's disease patients. The samples also had similar tissue quality and were from the brain's prefrontal cortex, one of the less studied areas for the disease. The prefrontal cortex does not show neuronal death to the same extent as the substantia nigra, although it displays molecular and pathological modifications during the disease process, while also being responsible for the dementia present in a large proportion of Parkinson's disease patients.

Results of the expression experiment showed that the gene FOXO1 had increased expression in the brain tissue samples with known Parkinson's disease. FOXO1 is a transcriptional regulator that can modify the expression of other genes. Further examination of the FOXO1 gene showed that two single-nucleotide polymorphisms (SNPs), or DNA sequence variations, were significantly associated with age at onset of Parkinson's disease.

"Our hypothesis is that FOXO1 acts in a protective manner by activating genes and pathways that fight the neurodegeneration processes," said Dumitriu. "If this is correct, there could be potential to explore FOXO1 as a therapeutic drug target for Parkinson's disease."

Provided by Boston University Medical Center