{
  "abstract": "Background Brain atrophy is increasingly used as an outcome measure in clinical trials in relapsing-remitting multiple sclerosis (RRMS), but little is known about how chronological age interacts with MS-specific effects. For instance, while annual brain atrophy rates typically increase with age in healthy individuals, MS patients tend to exhibit decreasing atrophy rates over time.Methods We investigated the relationship between age and brain volume in a large dataset of 4241 trial participants with RRMS. We used pooled individual-participant data from phase 3 clinical trials with 96 weeks follow-up, which included both active treatment and placebo/comparator arms. Participants were categorised into seven groups based on chronological age (18–24 years, 25–30 years, 31–35 years, 36–40 years, 41–45 years, 46–50 years, 51–56 years). We performed multilevel linear mixed-effects regression analyses to examine differences between age groups in normalised whole brain volume (NWBV), thalamus grey matter volume (NThGMV), grey matter volume (NGMV) and white matter volume at baseline and their changes over follow-up. We also studied how disease duration influenced these relationships using similar models.Results Older participants showed significantly lower NWBV, NGMV and NThGMV at baseline than younger participants. Most importantly, older participants exhibited lower rates of atrophy during follow-up, particularly in the thalamus. This association was consistent across all disease duration subgroups.Conclusions Older participants had more severe atrophy when enrolled into trials, but slower (thalamic) atrophy rates, independent of disease duration over time. Together, these findings emphasise that age should be taken into account when designing clinical trials that use brain atrophy as an outcome measure.",
  "authors": [
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands",
        "MS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Sezgi Kaçar"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "David R van Nederpelt"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Julia R Jelgerhuis"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Eline M E Coerver"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Joep Killestein"
    },
    {
      "affiliations": [
        "Department of Health Sciences (DISSAL), University of Genova, Genova, Italy",
        "Ospedale Policlinico San Martino IRCCS, Genova, Italy"
      ],
      "name": "Maria Pia Sormani"
    },
    {
      "affiliations": [
        "Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK",
        "National Institute for Health and Care Research (NIHR) University College Hospitals (UCLH) Biomedical Research Centre (BRC), London, UK"
      ],
      "name": "Olga Ciccarelli"
    },
    {
      "affiliations": [
        "NeuroRx Research and Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada",
        "McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"
      ],
      "name": "Douglas L Arnold"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Zoé L E van Kempen"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "B M J Uitdehaag"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands",
        "Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK",
        "Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK"
      ],
      "name": "Frederik Barkhof"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Marcus W Koch"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Menno M Schoonheim"
    },
    {
      "affiliations": [
        "Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK",
        "McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"
      ],
      "name": "Arman Eshaghi"
    },
    {
      "affiliations": [
        "MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Eva M M Strijbis"
    }
  ],
  "title": "Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis",
  "uid": "a6d53a22-28ba-519d-b233-058332a59e92"
}