Frontiers in Neurology (Sep 2024)

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients

  • Edoardo Nicolò Aiello,
  • Valeria Elisa Contarino,
  • Giorgio Conte,
  • Giorgio Conte,
  • Federica Solca,
  • Beatrice Curti,
  • Alessio Maranzano,
  • Silvia Torre,
  • Silvia Casale,
  • Alberto Doretti,
  • Eleonora Colombo,
  • Federico Verde,
  • Federico Verde,
  • Vincenzo Silani,
  • Vincenzo Silani,
  • Chunlei Liu,
  • Claudia Cinnante,
  • Fabio Maria Triulzi,
  • Fabio Maria Triulzi,
  • Claudia Morelli,
  • Barbara Poletti,
  • Barbara Poletti,
  • Nicola Ticozzi,
  • Nicola Ticozzi

DOI
https://doi.org/10.3389/fneur.2024.1426841
Journal volume & issue
Vol. 15

Abstract

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BackgroundThis study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients.MethodsA total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume.ResultsHigher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks.DiscussionIron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

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