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

Antonio Canosa; Alessio Martino; Umberto Manera; Alessandro Giuliani; Rosario Vasta; Francesca Palumbo; Maurizio Grassano; Silvia Daniela Morbelli; Matteo Pardini; Agostino Chiaravalloti; Orazio Schillaci; Klaus Leonard Leenders; Rosalie Vered Kogan; Giulia Polverari; Grazia Zocco; Francesca Di Pede; Filippo De Mattei; Sara Cabras; Enrico Matteoni; Cristina Moglia; Andrea Calvo; Adriano Chiò; Marco Pagani

doi:10.1111/ene.16588

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

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

Authors

Antonio Canosa^{1

2

3}, Alessio Martino⁴, Umberto Manera^{1

2}, Alessandro Giuliani⁵, Rosario Vasta¹, Francesca Palumbo¹, Maurizio Grassano¹, Silvia Daniela Morbelli^{6

7}, Matteo Pardini^{8

9}, Agostino Chiaravalloti^{10

11}, Orazio Schillaci¹⁰, Klaus Leonard Leenders^{12

13}, Rosalie Vered Kogan¹³, Giulia Polverari¹⁴, Grazia Zocco¹, Francesca Di Pede¹, Filippo De Mattei¹, Sara Cabras^{1

15}, Enrico Matteoni¹, Cristina Moglia^{1

2}, Andrea Calvo^{1

2

16}, Adriano Chiò^{1

2

3

16}, Marco Pagani^{3

17}

Affiliations

¹ ALS Centre, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
² Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Neurology Unit 1U, Turin, Italy.
³ Institute of Cognitive Sciences and Technologies, C.N.R, Rome, Italy.
⁴ Department of Business and Management, LUISS University, Rome, Italy.
⁵ Environment and Health Department, Istituto Superiore di Sanità, Rome, Italy.
⁶ Department of Medical Sciences, University of Turin, Turin, Italy.
⁷ Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Nuclear Medicine Unit, Turin, Italy.
⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
⁹ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁰ Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.
¹¹ IRCCS Neuromed, Pozzilli, Italy.
¹² Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹³ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁴ Positron Emission Tomography Centre AFFIDEA-IRMET S.p.A, Turin, Italy.
¹⁵ Center for Neuroscience, University of Camerino, Camerino, Italy.
¹⁶ Neuroscience Institute of Turin (NIT), Turin, Italy.
¹⁷ Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.

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.

MeSH terms

Adult
Aged
Amyotrophic Lateral Sclerosis* / diagnostic imaging
Amyotrophic Lateral Sclerosis* / metabolism
Brain* / diagnostic imaging
Brain* / metabolism
Female
Fluorodeoxyglucose F18*
Humans
Male
Middle Aged
Positron-Emission Tomography*
Sex Characteristics*

Substances

Fluorodeoxyglucose F18

Abstract

MeSH terms

Substances

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