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Aspartic Acid in the Hippocampus: A Biomarker for Postoperative Cognitive Dysfunction

Postoperative cognitive dysfunction is the deterioration of cognitive performance after anesthesia and surgery, and manifests as impairments in short-term memory, concentration, language comprehension, and social integration skills.

Researchers Agree that Alzheimer’s Test Results Could be Released to Research Participants

A leading group of Alzheimer’s researchers contends that, as biomarkers to detect signals of the disease improve at providing clinically meaningful information, researchers will need guidance on how to constructively disclose test results and track how disclosure impacts both patients and the data collected in research studies. A survey conducted by a group including experts from the Perelman School of Medicine at the University of Pennsylvania found that a majority of Alzheimer’s researchers supported disclosure of results to study participants. The study is published online in Neurology.

“While this is not a call to immediately tell subjects their biomarker results, it does show that the field is moving to a point where experts want to share valid and meaningful results with participants,” said co-senior author Jason Karlawish, MD, professor of Medicine and Medical Ethics and Health Policy. “As we gain more data on the predictive abilities of these measurements, we will need models and methods to effectively reveal results.”

The study surveyed 139 Alzheimer’s clinical trial leaders and coordinators from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in April 2012, just before the U.S. Food and Drug Administration approved the amyloid-binding radiotracer known as Amyvid (florbetapir). 73 percent of respondents supported disclosing amyloid imaging results to study participants with mild cognitive impairment, whereas 58 percent supported giving amyloid imaging results to those with normal cognition.

Six themes emerged from the survey, regarding participant preferences and cognition levels, researchers’ requests to develop standardized counseling procedures, participant education, and standardization of data-gathering, and concerns regarding potential harms and benefits to participants, as well as the ways disclosure could impact study results.

Currently, ADNI has a policy to not disclose results to participants, but the survey showed a growing trend of experts who would favor revising this policy. In addition to finding amyloid imaging results valuable, Alzheimer’s experts also valued other biomarker data collected in ADNI, such as spinal fluid tests, PET imaging, and other psychometric tests, suggesting that if amyloid imaging results were allowed to be disclosed, it would likely lead to disclosure of other test results.

Study: Using AD biomarker research results for clinical care [Neurology] 

Source: EurekAlert!

Spinal Fluid Biomarkers of AD and Brain Functional Network Integrity on Imaging Studies

Both Aß and tau pathology appear to be associated with default mode network integrity before clinical onset of Alzheimer disease (AD), according to a study by Liang Wang, M.D., and colleagues at Washington University in St. Louis, Missouri.

Accumulation of Aß and tau proteins, the pathologic hallmarks of AD, starts years before clinical onset. Pathophysiological abnormalities in the preclinical phase of AD may be detected using cerebrospinal fluid (CSF) or neuroimaging biomarkers, according to the study background.

A total of 207 older adults with normal cognition participated in the cross-sectional group study. Researchers examined the relationship between default mode network integrity and cerebrospinal fluid biomarkers of Alzheimer disease pathology in cognitively normal older individuals using resting-state functional connectivity magnetic resonance imaging.

According to the study results, decreased cerebrospinal fluid Aß42 and increased cerebrospinal fluid phosphorylated tau181 were independently associated with reduced default mode network integrity, with the most prominent decreases in functional connectivity observed between the posterior cingulate and medial temporal regions (regions of the brain associated with memory). Observed reductions in functional connectivity were unattributable to age or structural atrophy in the posterior cingulate and medial temporal areas.

Study: Cerebrospinal Fluid Aβ42, Phosphorylated Tau181, and Resting-State Functional Connectivity [JAMA Neurology]

Source: EurekAlert!

Big Data From Alzheimer’s Disease Whole Genome Sequencing Will Be Available to Researchers Due to Novel Global Research Database

The Alzheimer’s Association and the Brin Wojcicki Foundation announced recently that massive amounts of new data have been generated by the first “Big Data” project for Alzheimer’s disease. The data will be made freely available to researchers worldwide to quickly advance Alzheimer’s science.

Discussed recently at the Alzheimer’s Association International Conference (AAIC) 2013 in Boston, the project obtained whole genome sequences on the largest cohort of individuals related to a single disease – more than 800 people enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

The genome sequencing data – estimated to be 200 terabytes – will be housed in and available through the Global Alzheimer’s Association Interactive Network (GAAIN), a planned massive network of Alzheimer’s disease research data made available by the world’s foremost Alzheimer’s researchers from their own laboratories, and which also is being publicly announced today at AAIC 2013. GAAIN is funded by an initial $5 million dollar investment by the Alzheimer’s Association, made possible due to the generous support of donors.

“The Alzheimer’s Association is committed to creating open access to research data, and we believe GAAIN will transform how neuroscience data is shared and accessed by scientists throughout the world,” said Maria Carrillo, Ph.D., Alzheimer’s Association vice president of Medical and Scientific Relations. “By fostering a higher level of global data sharing, GAAIN will accelerate investigation and discovery in Alzheimer’s through a system comparable to a search engine like Google or Bing for relevant data.”

“With the addition of more than 800 whole genomes on ADNI subjects that can be linked to the current rich dataset, ADNI data will be even more useful to scientists who are seeking new approaches to treatment and prevention of Alzheimer’s disease,” said Robert C. Green, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, who led the ADNI sequencing project. “ADNI is a leader in open data sharing, having provided clinical, imaging and biomarker data to over 4,000 qualified scientists around the world, which has generated over 700 scientific manuscripts.

First, Massive Whole Genome Sequencing Project in Alzheimer’s Disease

Whole genome sequencing determines all six billion letters in an individual’s DNA in one comprehensive analysis. The raw data from the ADNI project is being made available to qualified scientists around the globe to mine for novel targets for risk assessment, new therapies, and much-needed insight into the causes of the fatal brain disease. The new data may enable scientists to better understand how our genes cause and are affected by bodily changes associated with Alzheimer’s disease.

ADNI 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 in body fluids, structural changes in the brain, and measures of memory; the hope is to improve early diagnosis and accelerate the discovery of new treatments. ADNI is led by Principal Investigator Michael W. Weiner, M.D., of the University of California San Francisco and the San Francisco VA Medical Center. Dr. Green collaborated on managing the sequencing efforts with Arthur Toga, Ph.D., of UCLA and Andrew J. Saykin, Psy.D., of Indiana University. The actual genome sequencing was performed at Illumina, Inc.

ADNI is a public-private research project led by the National Institutes of Health (NIH) 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 Global Alzheimer’s Association Interactive Network (GAAIN)

Data-sharing has already greatly benefitted scientific disciplines such as genetics, molecular biology, and the physical sciences. Data-sharing in genetics has led to dramatic advances in understanding the risk factors underlying complex diseases. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a compelling example of dozens of geographically-dispersed researchers working together to share their data while making it freely available to others for analysis and publication.

“GAAIN is similar in spirit and goals to other ‘big data’ initiatives that seek to greatly improve the tools and techniques needed to access, organize, and make discoveries from huge volumes of digital data,” Carrillo said. “The advent of cloud computing makes it possible to link databases throughout the world and expand their data processing capability significantly to benefit the research community.”

Carrillo will supervise the development of GAAIN in conjunction with co-principal investigators Art Toga, Ph.D., of the Laboratory of Neuro Imaging (LONI) at the University of Southern California and Giovanni Frisoni, M.D., of the National Center for Alzheimer’s Disease Research and Care and the Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fatebenefratelli Hospital, Italy. Enrique Castro-Leon, Ph.D., who will serve as a consultant, is an enterprise and data center architect for strategic partner Intel Digital Enterprise Group.

GAAIN is built on an international database framework already in use by thousands of scientists and local computational facilities in North America and Europe. The network makes research data available free-of-charge for searching, downloading, and processing across a cloud-based, grid-network infrastructure accessible anywhere through Internet access.

The key to GAAIN’s innovation is its federation of data, which is unprecedented for such a system. GAAIN leadership will invite scientists conducting qualified studies to become partners by permitting GAAIN to link directly to their databases. This will enable researchers to add continually to their data sets and keep all data in GAAIN current and dynamic. It also will enable the scientists to retain control over access to their data, which the Association believes will be important to encouraging participation.

“This is unprecedented and of the utmost importance in brain research, where sometimes thousands of examples are required to observe even the smallest change in the brain,” said Giovanni Frisoni, M.D., neurologist and deputy scientific director at the National Center for Alzheimer’s Disease Research and Care at the IRCCS. He will lead the work of GAAIN in Europe.

“Through GAAIN we envision combining massive amounts of data from multiple sources across many subjects participating in numerous studies,” said Art Toga, Ph.D., professor of neurology at UCLA and director of LONI. “This will provide more statistical power than ever before.”

Source: Alzheimer’s Association

NIH Launches Collaborative Effort to find Biomarkers for Parkinson’s

A new initiative aims to accelerate the search for biomarkers — changes in the body that can be used to predict, diagnose or monitor a disease — in Parkinson’s disease, in part by improving collaboration among researchers and helping patients get involved in clinical studies.