Alzheimer's Disease Neuroimaging Initiative

Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a worldwide project that provides reliable clinical data for the research of pathology principle, prevention and treatment of Alzheimer’s disease (AD). Multiple research groups contribute their findings of the biological markers to the understanding of the progression of Alzheimer’s disease in the human brain. The project enlists scientists and executives from the National Institutes of Health, the Food and Drug Administration, drug and medical-imaging companies, universities and nonprofit groups.

The initiative's defining characteristic is the commitment by all groups to publish and relinquish ownership of their data and findings as soon as possible, i.e., without waiting for the completion of their research. Collaborators also agreed to forgo any patent opportunities. The current focus is to measure the levels of certain proteins in the cerebrospinal fluid of people who may have Alzheimer's or may go on to develop it.

Primary aims

• Understand the pathology of AD by using biomarkers and diagnose AD at its earliest stage
• Provide clinical trials results from worldwide research to support the new methods in intervening, preventing and treating AD
• Continue and improve the sharing of database

Clinical trial Subjects

People who suffer from:

• Any kind of dementia
• Alzheimer’s disease (AD)
• Mild cognitive impairment
• Other memory problems

Three stages

• ADNI 1

ADNI was launched in October 2004 (http://www.adni-info.org). At this stage, the aim was to find more accurate diagnose method in order to detect AD in the earliest stage and define the pathology using biological markers. ADNI tested various existed brain-imaging techniques, such as PET (Positron Emission Tomography) and MRI (Magnetic Resonance Imaging) to see whether they could be combined to detect early stage AD. In addition, subjects who have mild cognitive decline and memory loss problems are recruited to clinical trials. A series tests are conducted, including amyloid PET scans, glucose PET scans, MRI scans, lumbar punctures for CSF, blood tests, neuropsychological tests and tests of psychiatric function for mood. The biomarkers are used to track the progression of AD at the early stage. Then, these biomarker data are collected and analyzed to determine the progress of cognitive decline, as well as assisting researchers to develop new methods as a result testing the effectiveness of alternative detective methods.

• ADNI GO

The second stage of ADNI started in June 2009 and continued till 2011. ADNI GO was based on the researches of ADNI, developing standardized methods for clinical tests according to the previous ADNI work. 200 subjects suffering from early mild cognitive impairment (MCI) participated in the project in ADNI GO stage, helping the researchers to have a better understanding of the cognitive decline in the early stage.

• ADNI 2

ADNI 2 is the third stage of the whole project which started in 2011. The aim of this stage is to compare the cerebrospinal fluid, genetics and the assessments of the cognitive procession between aged people who are not suffering from AD and those who have mild symptoms of AD or other relative dementia.

Accomplishments

Developed methods for early detection of AD

Develop detective methods, such as CSF biomarkers, β-amyloid 42, tau and amyloid PET for early stage AD. The progression of AD in the early stage can be tracked in patients with mildly AD or even patients who have had apparent symptoms.

Developed standardized methods for clinical tests

• Magnetic Resonance Imaging (MRI)
• Positron Emission Tomography (PET)
• Cerebrospinal Fluid (CSF) biomarkers

Established ADNI database

Companies, governments and academic researchers have combined to acquire more than 3,200 downloads of the entire data set and almost a million downloads of the data sets containing brain scan images.

• ADNI Electronic Data Capture (EDC)

The ADNI Electronic Data Capture (EDC) is used by ADNI research sites to view, enter, and update clinical data collected for ADNI, ADNI GO, and ADNI 2. However, the EDC is not available to outside researchers.

• LONI data archive

Research sites use the LONI data archive to upload MRI and PET scans guided for ADNI. At the same time, ADNI Cores utilize LONI for supervising quality control checks and storing reconstructed images through downloading scans. Researchers worldwide from this site have access to data from ADNI’s study participants in North American, including AD patients, mild cognitive impairment subjects and elderly controls.

Main findings

Researches found that beta amyloid in the brain might have certain relationship with cognitive decline. According to the longitudinal study among people with mild symptoms of AD or relative dementias, people having amyloid in their brains experience more rapid progress of cognitive decline than those who have not. Even among normal people, amyloid in the brain increases the risk of AD. In addition, the change of the hippocampus area in the brain is one of the causes that lead to cognitive decline. These findings may contribute to improvement of AD pathology detection and effective treatments.It has been identified that MRI is the most effective technology of progression tracking. In comparison to other existed technology, it shows the greatest change.

Global collaboration of AD research

ADNI database was set up for AD data sharing among academia, government and industry researchers. The data comes from 350 published articles and approximately 2500 researchers emerged from ADNI database. Furthermore, after the success of ADNI project in the USA, some similar projects were launched in Japan, Australia, Europe, China, Taiwan, and Korea, improving the worldwide research of AD.

History

The idea for the collaboration, emerged about 10 years ago during a casual conversation between Neil S. Buckholtz, chief of the Dementias of Aging Branch at the National Institute on Aging (NIA), Dr. William Potter, a neuroscientist at Eli Lilly and Company "We wanted to get out of what I called 19th-century drug development — give a drug and hope it does something," Dr. Potter recalled in an interview on Thursday. "What was needed was to find some way of seeing what was happening in the brain as Alzheimer's progressed and asking if experimental drugs could alter that progression."

In conversation with NIA director Dr. Richard J. Hodes, Dr. Steven M. Paul, a former scientific director at the National Institute of Mental Health who had recently left to head central-nervous-system research at Eli Lilly, offered to ask other drug companies to raise money. Dr. Paul was on the board of the Foundation for the National Institutes of Health, which raises private funds on behalf of the institutes and aided the effort. The collaboration officially began in 2003.

Funding

Prior to the collaboration, no individual project had the resources to undertake the biomarker project, which would require testing 800 subjects for possible biomarkers, some with normal memories, some with memory impairment, some with Alzheimer’s, and following them for years.

The National Institute on Aging (NIA) the National Institute of Bioimaging and Bioengineering (NIBIB) are the two major sponsors of the ADNI project. All up in total, 60 million dollars has been received into the foundation, of which 40 million dollars is from these two institutes.The rest 20 million dollars sponsored the pharmaceutical Industry and some foundations, and donation of foundation for the NIH. The Northern California Institute can get awarded funds for Research and Education, locating at the Veterans Administration Medical Center, San Francisco, attached to the University of California San Francisco. Besides, there are other organizations supporting this work as well, such as the Veteran’s Administration Office of Research and Development.In 2010, due to the federal stimulus package, ADNI was funded by 24 million dollars. Thus, the project began its second stage, ADNI GO. A year later, ADNI2 was progressing rapidly as a result of an additional 70 million dollars.

• FNIH

The FNIH focuses on donation from the private donor for ADNI, and it has got more than 45 million dollars already.The United States Congree established FNIH to insist the mission of the NIH, which is improving health through scientific discovery in the search for cures. The basic purpose for the NIH is a leader in recognizing and tackling intricacy scientific and health problems. The foundation is a non-profit, charitable organization that collects private factor capital for a wide range of unique project portfolio that complement and strengthen the focus of the NIH priorities and activities.

• PPSB

The full name of PPSB is Private Partner Scientific Board which runs as an independent, open, and pre-competitive forum for all private factor partners in ADNI. Not only can PPSB share information on issues relevant to the project, it can offer scientific and private factor point of view and expertise as well. The NIH (FNIH) can convene the PPSB by the Foundation.

Biomarkers

The candidate biomarkers are not necessarily definitive. Additional study is necessary to determine how many people who have them actually get the disease.

Further question that need to be solved

• The effects of the amyloid in the brain

Researches found that people who have amyloid in their brains are exposed to a higher risk, experiencing more rapid progress of cognitive decline than those who have not. However, the reason why some people have amyloid while others do not is still in suspense. Researchers believe genetics might be one determinant but not limited to it. In addition, some people with amyloid are free from memory loss problems while others suffer from AD or relative dementia. These questions are expected to be answered by the continued ADNI project.

Other collaborations

The initiative has served as a model for similar efforts against Parkinson's disease. A $40 million project to look for Parkinson's biomarkers, sponsored by the Michael J. Fox Foundation, plans to enroll 600 study subjects in the United States and Europe. ADNI "is the precedent," said Holly Barkhymer, foundation spokeswoman.

ADNI’s anagram DIAN, the Dominantly Inherited Alzheimer Network, based at Washington University in St Louis, is studying families with a genetic mutation that triggers early onset Alzheimer's. The mutation makes it possible to predict which members of a family are destined to get the disease, and to compare complete biochemistries with those of relatives who do not have the mutation.

External links

• "ADNI Home". Adni-info.org. Retrieved 2013-10-19.
• "World Wide Alzheimer's Disease Neuroimaging Initiative". Alz.org. Retrieved 2013-10-19.