Expanding ADNI: Alzheimer's Biomarker Study Embarks on Next Phase

Oct 12, 2016 at 05:37 pm by steve

The landmark Alzheimer's Disease Neuroimaging Initiative (ADNI) began in October 2004 with a goal of finding more sensitive and accurate methods to detect Alzheimer's disease (AD) in the early stages and to track progression by identifying and monitoring biomarkers. Last month, the NIH's National Institute on Aging announced an award of approximately $40 million over the next five years to launch ADNI3.

In addition, another $20 million is anticipated to be funneled into the program from private sector contributions through the Foundation for the National Institutes of Health. Pharmaceutical, imaging, and clinical trial management companies, along with non-profit organizations, have already contributed more than $14 million to ADNI3.

ADNI 3 is actually the fourth iteration of the long-running study that matches changes in clinical and cognitive testing with AD-related changes in biological markers found in blood, cerebrospinal fluid and DNA samples of study volunteers. Brain scans identify changes in brain volume, white matter integrity, functional connectivity between brain regions, glucose metabolism and the buildup of key proteins.

Michael Weiner, MD

Michael Weiner, MD - professor at University of California-San Francisco, director of the Center for Imaging of Neurodegenerative Disease for San Francisco VA Medical Center, principal investigator for ADNI ... and study participant - said ADNI is the largest project aimed at understanding the progression from normal aging to mild memory problems to Alzheimer's disease.

Ultimately, he continued, "The goal of ADNI is to facilitate and accelerate clinical trials to create effective treatments. We make all of the data of the project completely available to any scientist who wants it." Weiner added the de-identified data is available through a simple application process found at adni.loni.usc.edu.

"We are thrilled to embark on this next phase of discovery, enhanced by sophisticated new technologies and computational methods that we could only dream about when we launched the study in 2004," Weiner stated. "There are several big next steps," he said of continuing the large North American research project. "One, we'll continue to follow those we have been following for 12 years. Two, we're adding Tau PET." Weiner noted recent advances in imaging allow for measuring and tracking tau protein, thought to be one of two main culprits behind AD.

Weiner explained amyloid proteins are believed to form the plaques that are prevalent in the brains of those with Alzheimer's, and the tau forms the tangles. "The amyloid accelerates the spread and growth of the tau and tangles. It's the tau tangles that cause the nerve damage ... and the nerve damage causes memory problems and ultimately dementia and disease," he continued of the prevailing thought behind AD.

In addition to the technologically advanced PET imaging, Weiner said this next phase of the project also includes a low-tech, but very insightful, test called the Financial Capacity Instrument. FCI assesses a volunteer's ability to make the mental calculations necessary to use a checkbook, make change and understand a bank statement, among other financial manipulations.

"The beauty of this test is that it has real-world application," Weiner said, adding it is also clinically meaningful. He explained, "If you start to get Alzheimer's disease, the ability to do those kind of calculations in your head is limited."

Another addition for ADNI3 is tapping into the power of the Internet to track cognitive changes in volunteers online through the Brain Health Registry (brainhealthregistry.org). Utilizing a confidential questionnaire and Cogstate - a computerized battery of simple tasks that measure processing speed, working memory, attention, and executive function - the team is looking for subtle changes in health, lifestyle, medical history and cognition.

"The more information we can collect on the Internet to help doctors manage their patients, the better," Weiner stated, adding the tool might eventually be used for AD screening and monitoring.

"It's all about trying to figure out who is at risk," he continued. "Not everyone is going to get AD." That said, the 2015 Alzheimer's Disease Facts and Figures report from the Alzheimer's Association estimated 5.3 million Americans had AD in 2015 with 5.1 million being 65 and older. The report added that about one-third of those 85 and older have the disease and noted the volume of AD is expected to swell as baby boomers age. "Alzheimer's is the third most common cause of death now," Weiner added.

The principal investigator, who was in his mid-60s when ADNI started and is now 75, is also a study volunteer. "I wanted to really, completely understand what was going on," Weiner said. "You learn a lot when you're a subject in your own research."

As ADNI3 recruiting rolls out this fall, the goal is to add up to another 600-1,000 volunteers over the age of 55 to join the 800 current participants at 60 sites across the United States and Canada. With ADNI investigators making their collected data widely available, the study has already played a role in more than 1,200 research papers, and data has been accessed by more than 8,500 researchers worldwide. The study's game-changing discoveries also have been credited with advancing clinical trial design and leading to the testing of promising interventions at early stages of the disease.

"ADNI has made a profound difference in clinical trials, developing and refining the biomarker tools needed to see Alzheimer's-related brain changes in the living brain - even in people free of symptoms. ADNI3 will play an even more influential role as these biomarkers are enlisted in the search for treatments for this devastating disorder," said Weiner.

"When there finally will be a treatment for Alzheimer's, I have great confidence that ADNI is certainly going to have played a role in that," he concluded.

For more information, go online to adni-info.org.

ADNI Notable Accomplishments

The Alzheimer's Disease Neuroimaging Initiative (ADNI) website lists the following among most notable accomplishments.

  • Developed methods for early detection of AD. Cerebrospinal fluid (CSF) biomarkers, β-amyloid 42 and tau, as well as amyloid PET, may reflect the earliest steps in AD pathology in mildly symptomatic or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages.
  • Developed standardized methods for clinical tests for MRI, PET, and CSF biomarkers in a multicenter setting.
  • Demonstrated the feasibility and value of multicenter PET amyloid imaging. Amyloid phenotyping is expected to have a significant impact on future clinical trials and diagnosis of early Alzheimer's disease.
  • Garnered unanticipated observations. Some completely normal subjects having beta amyloid in their brain may be at increased risk for cognitive decline and dementia associated with Alzheimer's disease pathology.
  • Resulted in new findings. The study uncovered how changes in the structure of the hippocampus-area of the brain are more likely to develop dementia- may help detect disease progression and effectiveness of potential treatments.
  • Stimulated the development of a worldwide Alzheimer's collaboration. By making study data publicly available and easily accessible, ADNI has facilitated academic, government and industry research.
  • Expanded the global impact of furthering AD research. ADNI-like programs have now been established in Australia, Europe and Asia.


ADNI Research Database

Biogen Study in Nature

Sections: Clinical

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