Rates of atrophy measured from serial MRI precedes symptom onset in Alzheimer’s disease, and may be a useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. 52 healthy individuals (72.3±6.9 years) from AIBL had serial (0, 18m, 36m) MRI, (0, 18m) PiB PET and clinical data. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over three years, rates of whole brain atrophy (p<0.001), left and right hippocampal atrophy (p=0.001, p=0.023) and ventricular expansion (p<0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p=0.003). Acceleration of hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p<0.05). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is pre-symptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the pre-symptomatic phase.