Anatomical Grounding and Leakage-Aware Multimodal Contrastive Learning for Alzheimer's Disease Classification from Structural MRI

Abstract

Deep networks trained on structural MRI for Alzheimer's disease (AD) staging often reach reasonable accuracy while attending to anatomically irrelevant regions, and multimodal models that add clinical tables frequently rely on variables that were used to assign the diagnostic label in the first place. We study both issues with a deliberately lightweight slice-based encoder (ResNet18 with a one-layer Transformer over slices) on 1,075 baseline T1-weighted scans from ADNI-1. First, we use FastSurfer segmentations as an anatomical reference: YOLOv8 models trained on segmentation-derived labels localize Alzheimer-relevant structures with mAP_50 above 0.96, and a Grad-CAM comparison shows that the image-only classifier frequently attends to the skull, orbits and background. Second, we adapt a CLIP-style image - tabular contrastive framework and organize ADNIMERGE variables along a label-leakage spectrum. Fusion with cognitive scores yields 87.3% three-way accuracy, which we treat as a leakage-driven upper bound rather than an imaging result; fusion with regional volumes yields 73.0%. We observe that the choice of contrastive target changes what the image encoder learns: on MCI vs. CN, the image-only head reaches 52.4% when the encoder is aligned to cognitive scores and 73.8\% when aligned to volumes, although no tabular input is used at inference. Third, restricting the input to a per-subject crop of the medial temporal lobe raises image-only three-way accuracy from 58.7% to 65.1%. All results come from single runs on a small balanced test set, and we report confidence intervals and the protocol differences that prevent direct comparison with published numbers.