Validation of a novel neuroimaging signature for dementia and clinical Alzheimer's disease in the population-based Rotterdam study

Background: A novel neuroimaging signature of regional cortical thickness on brain MRI recently showed high potential for Alzheimer's disease and related dementias (ADRD) risk stratification in the community. How these findings translate to other populations, remains undetermined. Objective: We aimed to replicate this novel ADRD neuroimaging marker in the population-based Rotterdam Study. Methods: We included all participants from the population-based Rotterdam Study with brain-MRI between 2005–2016, and derived the signature using FreeSurfer. We computed hazard ratios and C-statistics for 10-year dementia risk, and betas for cross-sectional associations with cognition, comparing the novel signature to hippocampal volume, mean cortical thickness, and another cortical thickness signature (Dickerson's). Results: Of 3249 participants (mean age 71.3 ± 8.0 years), 294 developed dementia (74.8% clinical AD) during a mean follow-up of 8.1 years. The novel ADRD signature had similar magnitude of associations as Dickerson's signature and cortical thickness for AD dementia (HR per 1-SD increase 0.87;0.78–0.96), but performed worse than all markers for all-cause dementia. Of the four neuroimaging markers, hippocampal volume showed the strongest associations with both risk of all-cause dementia and clinical AD dementia. The ADRD had the weakest association with general cognitive function (β per 1-SD increase 0.04;0.02–0.06), and executive function (β per 1-SD increase 0.02;0.00–0.04), followed by cortical thickness and Dickerson's, and hippocampal volume showed the strongest associations. Conclusions: In this community-based study, the novel cortical thickness signature did not outperform hippocampal volume for dementia risk stratification. The importance of replication studies underlines the value of the current study. Replicating research findings is essential to establish robust biomarkers for dementia risk prediction.