people. ADNI studies have focused on two aspects of clinical trials in particular: 1) how best to select trial participants who don't yet show any signs of cognitive impairment but who are at a high risk of developing AD (subject selection); and 2) how to detect the effect of a therapy (outcome measures). Subject selection ADNI studies have shown that people who are β-amyloid positive or have a small hippocampal volume, or carry an APOE ε4 allele are at a higher risk for AD. Therefore, clinical trial participants can be selected using these criteria. (39). Moreover, use of the selection strategy can reduce the number of participants required to detect a treatment effect over feasible trial (for example 3 years). β-amyloid positivity. Currently, the phase 3 A4 trial testing the anti-amyloid antibody solanezumab, uses β-amyloid positivity to select elderly participants with no outward signs of AD. Hippocampal volume. Hippocampal volume can differentiate between MCI patients who will go on to develop AD from those who are on different disease pathways. This reduces the number of participants required for effective clinical trials. Hippocampal volume is the first imaging biomarker to be qualified, with the help of ADNI data, by the European Medicines Agency to select patients for clinical trials. ADNI also contributed to the development of a standardized technique to manually measure hippocampal volume from MRI scans for use in clinical trials. APOE ε4 allele. As this allele is the biggest risk factor for late onset AD, it is commonly used in subject selection. Outcome measures In the US, only cognitive tests have been approved as outcome measures for detecting clinical change in AD clinical trials. Studies using ADNI data have helped refine these tests to be more sensitive to very early changes in cognition. ADNI is working to develop imaging biomarkers such as various brain atrophy MRI measures as alternative outcome measures to these cognitive tests. Future directions ADNI-3 will follow current and additional patients with normal cognition, MCI, and AD for a further five years. The approach is unique to the study are: Use of web-based methods for cognitive assessment of patients in conjunction with the Brain Health Registry. Use of tau PET imaging to determine how tau tangles are related to amyloid levels and to cognition Development of tau PET as outcome measure to replace cognitive outcome measures for AD clinical trials Use of Human Connectome Project MRI