Explainable machine learning identifies candidate shared neuroanatomical features in Alzheimer’s and Parkinson’s via importance inversion transfer

Abstract

Despite significant neurobiological and pathological overlaps, Alzheimer’s and Parkinson’s diseases–the primary threats to healthy aging–are still managed as distinct clinical entities. Standard machine learning exacerbates this diagnostic fragmentation by prioritizing divergent markers over shared traits, thereby obscuring the invariant foundations of neurodegeneration. This study introduces Importance Inversion Transfer, an explainable machine learning framework designed to identify neuroanatomical invariants across the neurodegenerative spectrum. Prioritizing structural stability over discriminative utility isolates a shared pathological core consisting of ten regional volumetric anchors, validated through an inductive protocol with high diagnostic fidelity (AUC = 0.894). The identified morphological continuum between healthy aging and neurodegeneration delineates shared structural substrates consistent with–though not demonstrative of–a potential common early-phase vulnerability. Aligned with the Neurodegenerative Elderly Syndrome hypothesis, this evidence establishes a possible paradigm for early, system-level diagnosis.