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Age at symptom onset influences cortical thinning distribution and survival in amyotrophic lateral sclerosis

  • Functional Neuroradiology
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Abstract

Purpose

The lifetime risk of developing amyotrophic lateral sclerosis (ALS) increases in the elderly, and greater age at symptom onset has been identified as a negative prognostic factor in the disease. However, the underlying neurobiological mechanisms are still poorly investigated. We hypothesized that older age at symptom onset would have been associated with greater extra-motor cortical damage contributing to worse prognosis, so we explored the relationship between age at symptom onset, cortical thinning (CT) distribution, and clinical markers of disease progression.

Methods

We included 26 ALS patients and 29 healthy controls with T1-weighted magnetic resonance imaging (MRI). FreeSurfer 6.0 was used to identify regions of cortical atrophy (CA) in ALS, and to relate age at symptom onset to CT distribution. Linear regression analyses were then used to investigate whether MRI metrics of age-related damage were predictive of clinical progression. MRI results were corrected using the Monte Carlo simulation method, and regression analyses were further corrected for disease duration.

Results

ALS patients exhibited significant CA mainly encompassing motor regions, but also involving the cuneus bilaterally and the right superior parietal cortex (p < 0.05). Older age at symptom onset was selectively associated with greater extra-motor (frontotemporal) CT, including pars opercularis bilaterally, left middle temporal, and parahippocampal cortices (p < 0.05), and CT of these regions was predictive of shorter survival (p = 0.004, p = 0.03).

Conclusion

More severe frontotemporal CT contributes to shorter survival in older ALS patients. These findings have the potential to unravel the neurobiological mechanisms linking older age at symptom onset to worse prognosis in ALS.

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Code availability

Not applicable.

Data Availability

Raw data are available upon appropriate request.

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Acknowledgements

The authors are grateful to patients and healthy volunteers for participating in the study.

Funding

This work was supported by grants from Italian Ministry of Health (5x1000 2016).

Author information

Authors and Affiliations

  1. Department of Neuroradiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Pilar M. Ferraro, Claudia Rolla-Bigliani, Lucio Castellan & Luca Roccatagliata

  2. Department of Neurophysiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Corrado Cabona

  3. Department of Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Giuseppe Meo, Matteo Pardini, Matilde Inglese & Claudia Caponnetto

  4. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Matteo Pardini & Matilde Inglese

  5. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

    Luca Roccatagliata

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  1. Pilar M. Ferraro
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  2. Corrado Cabona
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Corresponding author

Correspondence to Pilar M. Ferraro.

Ethics declarations

Ethic approval

Retrospective analysis of the data was approved by the IRCCS Ospedale Policlinico San Martino Review Board.

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Written informed consent was obtained from each participant according to the institution’s procedures and the Declaration of Helsinki.

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Not applicable.

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We declare that we have no conflict of interest.

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Supplementary information

Supplementary Figure 1.

Three-dimensional reconstructed MR imaging maps show regions of significant cortical atrophy on the inflated surface in the left (L) and right (R) hemispheres in ALS patients (excluding the two genetic cases) compared to healthy controls (Montecarlo, p< 0.05). (JPG 273 kb)

Supplementary Figure 2.

Three-dimensional reconstructed MR imaging maps show regions of significant cortical thinning related to older age at symptoms onset on the inflated surface in the left (L) and right (R) hemispheres in ALS patients (excluding the two genetic cases) (Montecarlo, p< 0.05). (JPG 322 kb)

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Ferraro, P.M., Cabona, C., Meo, G. et al. Age at symptom onset influences cortical thinning distribution and survival in amyotrophic lateral sclerosis. Neuroradiology 63, 1481–1487 (2021). https://doi.org/10.1007/s00234-021-02681-3

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  • DOI: https://doi.org/10.1007/s00234-021-02681-3

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