29 Oct 2010

The much-awaited announcement that ADNI2 will go ahead was made 21 October 2010 by the National Institutes of Health. According to the NIH, the second phase of the Alzheimer’s Disease Neuroimaging Initiative will recruit an additional 550 volunteers, bringing the total number of subjects being followed to approximately 1,000. After the recent economic downturn, there was some doubt that sufficient funds could be raised for another ADNI round, but a combination of public and private support has met the hefty price tag of $62 million. The bulk of it, $40 million, will be provided by the NIH over the next five years. The balance will be funneled through the Foundation for the NIH from various not-for-profit organizations, including the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation, and the private sector, including pharmaceutical companies, such as Bristol-Myers Squibb, Pfizer, Eli Lilly and Company, Merck, GE Healthcare, and many others. All sponsors are listed in the NIH press release.

Most scientists in the field seem to think that ADNI1 was a resounding success, leading to more than 150 publications and a wealth of imaging, biomarker, and genetics data. “It was really a novel idea to put all the data in a public dataset that anyone can access, analyze, and write papers on, and that has been extremely successful,” said Neil Buckholtz, who oversaw the study for the NIA’s Division of Neuroscience. ADNI spurred similar efforts in Europe and Asia (see ARF related news story). Most recently the Parkinson’s field has taken up a similar challenge with the Parkinson’s Progression Markers Initiative (see ARF related news story), as has the field of frontotemporal dementias with the FTLD Neuroimaging Initiative.

Buckholtz told ARF that one of the major questions to be addressed in ADNI2 is just how early changes can be detected that are indicative of impending AD. In ADNI2, every participant has to consent to PET amyloid imaging in order to enroll. ADNI2 will use the F18-AV45 amyloid ligand rather than C11-PIB, because many more sites are capable of measuring the former. “That may make things technically more complicated, but the benefit is that everyone will be imaged for Aβ amyloid,” said Buckholtz. ADNI2 will also incorporate functional MRI, and some additional MRI modalities will be examined in sub-studies, including diffusion tensor imaging and arterial spin labeling.

All participants will also undergo lumbar punctures for collection of cerebrospinal fluid, which Buckholtz agrees is cheaper than imaging and is now generally seen as a more important analysis than when ADNI1 started. Buckholtz also said that through the FNIH biomarker consortium, data from a large plasma proteomics study have been analyzed and will go live on the ADNI site within the next few weeks. Based on this analysis of plasma from ADNI1 subjects, there will also be a proteomic study of ADNI1 CSF. “ADNI2 will test the idea that by looking at levels of not only Aβ, tau, and phospho-tau, but also of other proteins, we may be able to predict who progresses from MCI to AD, and maybe from normal to AD,” Buckholtz said.

ADNI2 invites controls and people with late mild cognitive impairment (MCI) from the original ADNI, and early MCI patients from its extension study ADNI-GO. New ADNI2 recruits will include controls, people with early and late MCI and those with mild AD. Volunteers will be recruited at 50 sites in the U.S. and five in Canada. For its part, the Canadian Institute of Health Research is providing $1.5 million.—Tom Fagan.