The Australian Imaging, Biomarkers and Lifestyle study of Ageing (AIBL) is a multicentre study of 600 healthy elderly persons, 200 individuals with Mild Cognitive Impairment (MCI) and 200 subjects with mild Alzheimer's disease (AD) with neuropsychological assessment and blood collection in all participants and PiB PET and MRI in 25% of each subgroup at baseline and 18 months. Both baseline and 18 month imaging data is available to researchers through the Alzheimer's Disease Neuroimaging Initiative (ADNI) website with the support of Alzheimer's Association. AIBL has sufficient similarity to ADNI to permit pooling of neuroimaging data and for validation of ADNI findings. The AIBL 18 month follow-up will be complete by February 2010. Baseline imaging of the AIBL cohort has further defined the significant role of ApoE-e4 in beta-amyloidogenesis, shown that amyloid deposition is almost inevitable with advanced age, that amyloid burden is similar at all ages in AD, and that secondary factors or downstream events play a more direct role than total amyloid burden in hippocampal atrophy and cognitive decline once dementia has developed. Preliminary analysis of the 18 month data shows that the rate of change in brain amyloid burden is of the order of 1-2% per year. Therefore much longer follow-up than 18 months will be required to fully assess the rate and pattern of amyloid deposition and its relationship to both structural and cognitive changes over time, and the predictive value for AD. This grant will permit 36 month follow-up with clinical assessment, MRI and PiB PET in the imaging subcohort of AIBL (287 subjects at baseline).