Comparing a pre-defined versus deep learning approach for extracting brain atrophy patterns to predict cognitive decline due to Alzheimer’s disease in patients with mild cognitive symptoms

BACKGROUND: Predicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is unclear if the predictive performance of MRI can be improved using entire brain images in deep learning (DL) models compared to using pre-defined brain regions. METHODS: A cohort of 332 individuals with SCD/MCI were included from the Swedish BioFINDER-1 study. The goal was to predict longitudinal SCD/MCI-to-AD dementia progression and change in Mini-Mental State Examination (MMSE) over four years. Four models were evaluated using different predictors: 1) clinical data only, including demographics, cognitive tests and APOE e4 status, 2) clinical data plus hippocampal volume, 3) clinical data plus all regional MRI gray matter volumes (N=68) extracted using FreeSurfer software, 4) a DL model trained using multi-task learning with MRI images, Jacobian determinant images and baseline cognition as input. Models were developed on 80% of subjects (N=267) and tested on the remaining 20% (N=65). Mann-Whitney U-test was used to determine statistically significant differences in performance, with p-values less than 0.05 considered significant. RESULTS: In the test set, 21 patients (32.3%) progressed to AD dementia. The performance of the clinical data model for prediction of progression to AD dementia was area under the curve (AUC)=0.87 and four-year cognitive decline was R(2)=0.17. The performance was significantly improved for both outcomes when adding hippocampal volume (AUC=0.91, R(2)=0.26, p-values <0.05) or FreeSurfer brain regions (AUC=0.90, R(2)=0.27, p-values <0.05). Conversely, the DL model did not show any significant difference from the clinical data model (AUC=0.86, R(2)=0.13). A sensitivity analysis showed that the Jacobian determinant image was more informative than the MRI image, but that performance was maximized when both were included. CONCLUSIONS: The DL model did not significantly improve the prediction of clinical disease progression in AD, compared to regression models with a single pre-defined brain region.