: 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.

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

Caligiore, Daniele
Conceptualization
;
Torsello, Simone
Data Curation
2026

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.
2026
Istituto di Scienze e Tecnologie della Cognizione - ISTC
Alzheimer’s disease
Brain morphometry
Explainable Artificial Intelligence (XAI)
Importance Inversion Transfer (IIT)
Neurodegenerative Elderly Syndrome (NES)
Parkinson’s disease
Structural anchors
System-level neurodegeneration
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/584445
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