Brain MRI volumetry and atrophy rating scales as predictors of amyloid status and eligibility for anti-amyloid treatment in a real-world memory clinic setting

Abstract

Predicting amyloid status is crucial in light of upcoming disease-modifying therapies and the need to identify treatment-eligible patients with Alzheimer's disease. In our study, we aimed to predict CSF-amyloid status and eligibility for anti-amyloid treatment in a memory clinic by (I) comparing the performance of visual/automated rating scales and MRI volumetric analysis and (II) combining MRI volumetric data with neuropsychological tests and APOE4 status. Two hundred ninety patients underwent a comprehensive assessment. The cNeuro cMRI software (Combinostics Oy) provided automated computed rating scales and volumetric analysis. Amyloid status was determined using data-driven CSF biomarker cutoffs (Aβ42/Aβ40 ratio), and eligibility for anti-Aβ treatment was assessed according to recent recommendations published after the FDA approval of the anti-Aβ drug aducanumab. The automated rating scales and volumetric analysis demonstrated higher performance compared to visual assessment in predicting Aβ status, especially for parietal-GCA (AUC = 0.70), MTA (AUC = 0.66) scores, hippocampal (AUC = 0.68), and angular gyrus (AUC = 0.69) volumes, despite low global accuracy. When we combined hippocampal and angular gyrus volumes with RAVLT immediate recall and APOE4 status, we achieved the highest accuracy (AUC = 0.82), which remained high even in predicting anti-Aβ treatment eligibility (AUC = 0.81). Our study suggests that automated analysis of atrophy rating scales and brain volumetry outperforms operator-dependent visual rating scales. When combined with neuropsychological and genetic information, this computerized approach may play a crucial role not only in a research context but also in a real-world memory clinic. This integration results in a high level of accuracy for predicting amyloid-CSF status and anti-Aβ treatment eligibility.

Keywords: Anti-amyloid treatment eligibility; Atrophy rating scales; Brain volumetry; Neuroimaging.

Fig. 1

Coronal 3D T1-weighted brain MRI scans with MTA = 3 bilaterally (left panel) and with GCA-P = 3 (right panel)

Fig. 2

Illustration of the structural segmentation from T1 3D images using cNeuro cMRI software

Fig. 3

ROC curves of the model combining hippocampus and angular gyrus and the model comprehensive of neuroimaging, neuropsychological, and genetic data. On the left is the global cohort, and the right in the prediction of the eligibility of anti-Aβ treatment