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. 2025 Jan;32(1):e16588.
doi: 10.1111/ene.16588.

Sex-related differences in amyotrophic lateral sclerosis: A 2-[18F]FDG-PET study

Antonio Canosa  1   2   3 , Alessio Martino  4 , Umberto Manera  1   2 , Alessandro Giuliani  5 , Rosario Vasta  1 , Francesca Palumbo  1 , Maurizio Grassano  1 , Silvia Daniela Morbelli  6   7 , Matteo Pardini  8   9 , Agostino Chiaravalloti  10   11 , Orazio Schillaci  10 , Klaus Leonard Leenders  12   13 , Rosalie Vered Kogan  13 , Giulia Polverari  14 , Grazia Zocco  1 , Francesca Di Pede  1 , Filippo De Mattei  1 , Sara Cabras  1   15 , Enrico Matteoni  1 , Cristina Moglia  1   2 , Andrea Calvo  1   2   16 , Adriano Chiò  1   2   3   16 , Marco Pagani  3   17
Affiliations

Sex-related differences in amyotrophic lateral sclerosis: A 2-[18F]FDG-PET study

Antonio Canosa et al. Eur J Neurol. 2025 Jan.

Abstract

Purpose: We investigated sex-related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC).

Methods: We collected two equal-sized groups of male (m-ALS) and female ALS (f-ALS) patients (n = 130 each), who underwent 2-[18F]FDG-PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age-matched healthy controls, half female (f-HC) and half male (m-HC). We compared brain metabolism of males and females separately for ALS and HC, including age as covariate. A differential network analysis was performed to evaluate brain connectivity.

Results: M-ALS showed relative hypometabolism of bilateral medial frontal, parietal and occipital cortices, and left temporal cortex, compared to f-ALS. In node-wise comparison, f-ALS showed significantly higher connectivity in right middle cingulate cortex and left superior and medial frontal gyrus. In HC we did not find any sex-related differences.

Conclusion: Sex resulted a major determinant of brain metabolism and connectivity in ALS patients.

Keywords: 2‐[18F]FDG‐PET; amyotrophic lateral sclerosis; brain connectivity; brain metabolism; sex differences.

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Conflict of interest statement

Matteo Pardini reports research support from Novartis and Nutricia and speakers fees from GE, Biogen and Merck. Andrea Calvo has received a research grant from Cytokinetics. Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Cytokinetics, Denali Therapeutics, Amylyx and AveXis. The other authors report no disclosures relevant to the manuscript.

Figures

FIGURE 1
FIGURE 1
Clusters of relative hypometabolism of male as compared to female ALS patients are marked in red and are reported on axial sections of a brain magnetic resonance imaging template and on the brain surface of a glass brain rendering (bottom right).
FIGURE 2
FIGURE 2
Whole‐brain metabolic connectivity of ALS females is represented on a 3D brain template. The spheres represent the nodes: The higher the size, the higher the metabolic connectivity. Red connections stand for positive correlations, the blue ones for negative correlations.
FIGURE 3
FIGURE 3
Whole‐brain metabolic connectivity of ALS males is represented on a 3D brain template. The spheres represent the nodes: The higher the size, the higher the metabolic connectivity. Red connections stand for positive correlations, the blue ones for negative correlations.
See this image and copyright information in PMC

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