Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis

Tedeschi, Gioacchino; Trojsi, Francesca; Tessitore, Alessandro; Corbo, Daniele; Sagnelli, Anna; Paccone, Antonella; D'Ambrosio, Alessandro; Piccirillo, Giovanni; Cirillo, Mario; Cirillo, Sossio; Monsurrò, Maria Rosaria; Esposito, Fabrizio

doi:10.1016/j.neurobiolaging.2010.07.011

« BackNeurobiology of Aging

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Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis

Gioacchino Tedeschi
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
- Corresponding author: Tel.: +39 081 5665004; fax: +39 081 5665095
Francesca Trojsi
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
Alessandro Tessitore
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
Daniele Corbo
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
Anna Sagnelli
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
Antonella Paccone
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
Alessandro D'Ambrosio
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
Giovanni Piccirillo
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
Mario Cirillo
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
Sossio Cirillo
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), 16149, Genoa, Italy
Maria Rosaria Monsurrò
- Department of Neurological Sciences, Second University of Naples, 80138, Naples, Italy
- Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, 80131, Naples, Italy
Fabrizio Esposito
- Department of Neuroscience, University of Naples “Federico II”, 80131, Naples, Italy
- Department of Cognitive Neuroscience, Maastricht University, 6200 MD, Maastricht, the Netherlands

Received 4 March 2010; received in revised form 2 June 2010; accepted 12 July 2010. published online 26 August 2010.
Corrected Proof

Abstract

We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters.

Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans.

The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity.

Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances.

Keywords: Amyotrophic lateral sclerosis (ALS), Resting-state functional magnetic resonance imaging (RS-fMRI), Independent component analysis (ICA), Default-mode network (DMN), Sensori-motor network (SMN)