Personalising Alzheimer's Disease progression using brain atrophy markers

INTRODUCTION: Neuroanatomical normative modelling can capture individual variability in Alzheimers Disease (AD). We used neuroanatomical normative modelling to track individuals disease progression in people with mild cognitive impairment (MCI) and patients with AD. METHODS: Cortical thickness and subcortical volume neuroanatomical normative models were generated using healthy controls (n[~]58k). These models were used to calculate regional Z-scores in 4361 T1-weighted MRI time-series scans. Regions with Z-scores <-1.96 were classified as outliers and mapped on the brain, and also summarised by total outlier count (tOC). RESULTS: Rate of change in tOC increased in AD and in people with MCI who converted to AD and correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of MCI progression to AD. Brain Z-score maps showed that the hippocampus had the highest rate of atrophy change. CONCLUSIONS: Individual-level atrophy rates can be tracked by using regional outlier maps and tOC.