Classification using fractional anisotropy predicts conversion in genetic frontotemporal dementia, a proof of concept

Brain Communications, vol. 2, pp. fcaa079

Abstract

Abstract Frontotemporal dementia is a highly heritable and devastating neurodegenerative disease. About 10–20% of all frontotemporal dementia is caused by known pathogenic mutations, but a reliable tool to predict clinical conversion in mutation carriers is lacking. In this retrospective proof-of-concept case-control study, we investigate whether MRI-based and cognition-based classifiers can predict which mutation carriers from genetic frontotemporal dementia families will develop symptoms (‘convert’) within 4 years. From genetic frontotemporal dementia families, we included 42 presymptomatic frontotemporal dementia mutation carriers. We acquired anatomical, diffusion-weighted imaging, and resting-state functional MRI, as well as neuropsychological data. After 4 years, seven mutation carriers had converted to frontotemporal dementia (‘converters’), while 35 had not (‘non-converters’). We trained regularized logistic regression models on baseline MRI and cognitive data to predict conversion to frontotemporal dementia within 4 years, and quantified prediction performance using area under the receiver operating characteristic curves. The prediction model based on fractional anisotropy, with highest contribution of the forceps minor, predicted conversion to frontotemporal dementia beyond chance level (0.81 area under the curve, family-wise error corrected P = 0.025 versus chance level). Other MRI-based and cognitive features did not outperform chance level. Even in a small sample, fractional anisotropy predicted conversion in presymptomatic frontotemporal dementia mutation carriers beyond chance level. After validation in larger data sets, conversion prediction in genetic frontotemporal dementia may facilitate early recruitment into clinical trials.

Authors 12

1. Rogier A. Feis corresponding Aachen Department of Radiology, Leiden University Medical Center Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

   Institute of Psychology, Leiden University, 2333 AK, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands

2. Jeroen van der Grond Aachen Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

3. Mark J.R.J. Bouts Aachen Department of Radiology, Leiden University Medical Center Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

   Institute of Psychology, Leiden University, 2333 AK, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands

4. Jessica L. Panman Aachen Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Erasmus MC

   Affiliation as printed

   Department of Neurology, Erasmus Medical Centre, 3015 GD, Rotterdam, the Netherlands

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

5. Jackie M. Poos Aachen Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Erasmus MC

   Affiliation as printed

   Department of Neurology, Erasmus Medical Centre, 3015 GD, Rotterdam, the Netherlands

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

6. Tijn M. Schouten Aachen Department of Radiology, Leiden University Medical Center Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

   Institute of Psychology, Leiden University, 2333 AK, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands

7. Frank de Vos Aachen Department of Radiology, Leiden University Medical Center Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

   Institute of Psychology, Leiden University, 2333 AK, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands

8. Lize Corrine Jiskoot Aachen Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Erasmus MC · University College London

   Affiliation as printed

   Dementia Research Centre, University College London, London, WC1N 3AR, UK

   Department of Neurology, Erasmus Medical Centre, 3015 GD, Rotterdam, the Netherlands

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

9. Elise G.P. Dopper Aachen Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Erasmus MC

   Affiliation as printed

   Department of Neurology, Erasmus Medical Centre, 3015 GD, Rotterdam, the Netherlands

   Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

10. Mark A. van Buchem Aachen Department of Radiology, Leiden University Medical Center Leiden Institute for Brain and Cognition

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

    Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands

11. John Cornelis Van Swieten

    Erasmus MC

    Affiliation as printed

    Department of Neurology, Erasmus Medical Centre, 3015 GD, Rotterdam, the Netherlands

12. Serge A.R.B. Rombouts Aachen Department of Radiology, Leiden University Medical Center Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Radiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands

    Institute of Psychology, Leiden University, 2333 AK, Leiden, the Netherlands

    Leiden Institute for Brain and Cognition, Leiden University, 2333 ZA, Leiden, the Netherlands