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

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.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-14
DOI
https://doi.org/10.64898/2026.04.10.717735
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Daniele Caligiore, Simone Torsello
bioRxiv (Cold Spring Harbor Laboratory)
Functional Brain Connectivity Studies
article

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

Daniele Caligiore, Simone Torsello
article en

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.

bioRxiv (Cold Spring Harbor Laboratory)
Libera Università Maria SS. Assunta (IT), Superconducting and other Innovative Materials and Devices Institute (IT), Institute of Cognitive Sciences and Technologies (IT)
U.S. Department of Defense, Alzheimer's Disease Neuroimaging Initiative, Fondazione Italiana Sclerosi Multipla, European Commission, International Science and Technology Center, National Institutes of Health
Openalex Percentile: Top 27%
Functional Brain Connectivity Studies
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