The ageing central nervous system in multiple sclerosis: the imaging perspective

Author:

Filippi Massimo12345ORCID,Preziosa Paolo125ORCID,Barkhof Frederik67,Ciccarelli Olga89,Cossarizza Andrea10,De Stefano Nicola11ORCID,Gasperini Claudio12,Geraldes Ruth1314,Granziera Cristina151617ORCID,Haider Lukas718,Lassmann Hans19,Margoni Monica123,Pontillo Giuseppe6720,Ropele Stefan21,Rovira Àlex22ORCID,Sastre-Garriga Jaume23ORCID,Yousry Tarek A24,Rocca Maria A125ORCID,Rocca M A,Sastre-Garriga J,Barkhof F,Ciccarelli O,de Stefano N,Filippi M,Gasperini Claudio,Kappos L,De Luca Gabriele,Enzinger C,Rovira À,Schoonheim M,Yousry T,

Affiliation:

1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute , 20132 Milan , Italy

2. Neurology Unit, IRCCS San Raffaele Scientific Institute , 20132 Milan , Italy

3. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute , 20132 Milan , Italy

4. Neurophysiology Service, IRCCS San Raffaele Scientific Institute , 20132 Milan , Italy

5. Vita-Salute San Raffaele University , 20132 Milan , Italy

6. Department of Radiology & Nuclear Medicine, Amsterdam UMC, Vrije Universiteit , 1081 HV Amsterdam , The Netherlands

7. Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London , London WC1N 3BG , UK

8. Queen Square MS Centre, UCL Institute of Neurology, UCL , London WC1N 3BG , UK

9. NIHR (National Institute for Health and Care Research) UCLH (University College London Hospitals) BRC (Biomedical Research Centre) , London WC1N 3BG , UK

10. Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia , 42121 Modena , Italy

11. Department of Medicine, Surgery and Neuroscience, University of Siena , 53100 Siena , Italy

12. Department of Neurosciences, S Camillo Forlanini Hospital Rome , 00152 Rome , Italy

13. Clinical Neurology, John Radcliffe Hospital, Oxford University Foundation Trust , Oxford OX3 9DU , UK

14. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford , Oxford OX3 9DU , UK

15. Department of Neurology, University Hospital Basel and University of Basel , 4031 Basel , Switzerland

16. Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel , 4031 Basel , Switzerland

17. Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel , 4031 Basel , Switzerland

18. Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna , 1090 Vienna , Austria

19. Center for Brain Research, Medical University of Vienna , 1090 Vienna , Austria

20. Department of Advanced Biomedical Sciences, University “Federico II” , 80138 Naples , Italy

21. Department of Neurology, Medical University of Graz , 8010 Graz , Austria

22. Neuroradiology Section, Department of Radiology, Hospital Universitari Vall d'Hebron , 08035 Barcelona , Spain

23. Neurology Department and Multiple Sclerosis Centre of Catalunya (Cemcat), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , 08035 Barcelona , Spain

24. Lysholm Department of Neuroradiology, UCLH National Hospital for Neurology and Neurosurgery, Neuroradiological Academic Unit, UCL Institute of Neurology , London WC1N 3BG , UK

Abstract

Abstract The interaction between ageing and multiple sclerosis is complex and carries significant implications for patient care. Managing multiple sclerosis effectively requires an understanding of how ageing and multiple sclerosis impact brain structure and function. Ageing inherently induces brain changes, including reduced plasticity, diminished grey matter volume, and ischaemic lesion accumulation. When combined with multiple sclerosis pathology, these age-related alterations may worsen clinical disability. Ageing may also influence the response of multiple sclerosis patients to therapies and/or their side-effects, highlighting the importance of adjusted treatment considerations. Magnetic resonance MRI is highly sensitive to age- and multiple sclerosis-related processes. Accordingly, MRI can provide insights into the relationship between ageing and multiple sclerosis, enabling a better understanding of their pathophysiological interplay and informing treatment selection. This review summarizes current knowledge on the immuno-pathological and MRI aspects of ageing in the central nervous system in the context of multiple sclerosis. Starting from immunosenescence, ageing-related pathological mechanisms, and specific features like enlarged Virchow-Robin spaces, this review then explores clinical aspects, including late-onset multiple sclerosis, the influence of age on diagnostic criteria, and comorbidity effects on imaging features. The role of MRI in understanding neurodegeneration, iron dynamics, and myelin changes influenced by ageing and how MRI can contribute to defining treatment effects in ageing multiple sclerosis patients, are also discussed.

Publisher

Oxford University Press (OUP)

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