Alzheimer Research Forum releases overview of Alzheimer’s Disease Neuroimaging Initiative

October 2008

The Alzheimer Research Forum (Alzforum), an authoritative Web resource, is releasing a six-part series on the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the largest study ever to fill a central knowledge gap in the Alzheimer disease field.

Announced in October 2004 and set to run until 2010, the ADNI is a public-private consortium that has engaged 58 research centers in the US and Canada in a massive effort to follow 819 research volunteers for three years. Beginning this week, the Alzforum reports on the first waves of much-awaited data generated by the study, and also takes readers behind the scenes for a look at the challenges that had to be overcome in getting so many groups to work together effectively.

ADNI set out to identify biological markers that can reliably foretell whether a still-healthy person is on the way to developing full-blown Alzheimer disease. Such markers are essential in order to test — and some day prescribe — treatments to slow down or prevent the disease.

Objective and quantitative ways to measure how quickly a person progresses with AD will enable future drug trials to be smaller and faster, and thereby attract investors who now shy away from AD drug development because its trials have a reputation of being costly and prone to failure.

The need for such markers is so universally acknowledged across academia and industry and at the FDA that both academic and industry leaders have set aside their usual competition around this goal.

Funded to the tune of US$64 million — $40 million from the National Institute on Aging, and $24 million to date from a consortium of pharmaceutical companies and private foundations — ADNI is a massive and complex five-year study.

The 58 participating research centers all conduct the same long list of tests in 819 people in exactly the same way, and upload all the information into a database that is freely accessible to qualified scientists around the world for analysis.

All academics studying neurodegeneration and every company developing AD drugs around the world can use the integrated database of ADNI results for their purposes. At this level, ADNI data are not subject to embargoes, journal subscription, or even peer review. Those factors apply later, as investigators from within and outside ADNI publish their own analyses of ADNI data in scientific journals.

For their part, the research volunteers made a big commitment. They undergo a range of tests over the course of several days at each 6-month visit — extensive clinical, neuropsychological tests, different kinds of brain imaging, blood test and even a spinal tap to look for telltale signs of impending AD in the cerebrospinal fluid.

The key to the success or failure of this huge, shared effort is standardization. Only if all research centers do things in exactly the same ways will they produce a large dataset that can speak with authority.

This is critical because at present, at least a dozen highly regarded labs have promising results on potential AD imaging and biochemical markers. However, each study, even if well performed within its scope and institution, has used small groups of different patients and done their work differently enough to make it impossible to compare the results and decide which candidate markers are indeed the best.

One of ADNI’s express goals is to vet candidate markers and imaging methods side by side so the best may ‘win’ and go on to modernize clinical drug trials. In essence, ADNI aims to speak with a loud voice over the cacophony of present-day research studies, and in this way to facilitate a consensus on biomarkers among scientists and federal regulators.

ADNI represents the latest example in a movement to standardize and to unify that has been gradually building in US Alzheimer science in the past decade (Other such examples are the NACC and the ADCS). It also has inspired similar studies in Japan, Europe, China, and Australia.

In its six-part report, the Alzforum describes how ADNI evolved from its origins in 2004 and is beginning to produce results. The Alzforum series delves into how well the standardization and co-ordination among all the participating groups has gone, and what the actual scientific results are.

The series is available at: www.alzforum.org/new/detail.asp?id=1939

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