The Alzheimer's Disease Neuroimaging Initiative: Annual change in biomarkers and clinical outcomes.

Background: The Alzheimer's Disease Neuroimaging Initiative Phase 1 (ADNI-1) is a multisite prospective study designed to examine potential cerebrospinal fluid and imaging markers of Alzheimer's disease (AD) and their relationship to cognitive change. The objective of this study was to provide a global summary of the overall results and patterns of change observed in candidate markers and clinical measures over the first 2 years of follow-up.

Methods: Change was summarized for 210 normal controls, 357 mild cognitive impairment, and 162 AD subjects, with baseline and at least one cognitive follow-up assessment. Repeated measures and survival models were used to assess baseline biomarker levels as predictors. Potential for improving clinical trials was assessed by comparison of precision of markers for capturing change in hypothetical trial designs.

Results: The first 12 months of complete data on ADNI participants demonstrated the potential for substantial advances in characterizing trajectories of change in a range of biomarkers and clinical outcomes, examining their relationship and timing, and assessing the potential for improvements in clinical trial design. Reduced metabolism and greater brain atrophy in the mild cognitive impairment at baseline are associated with more rapid cognitive decline and a higher rate of conversion to AD. Use of biomarkers as study entry criteria or as outcomes could reduce the number of participants required for clinical trials.

Conclusions: Analyses and comparisons of ADNI data strongly support the hypothesis that measurable change occurs in cerebrospinal fluid, positron emission tomography, and magnetic resonance imaging well in advance of the actual diagnosis of AD.