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From the Department of Psychiatry and Psychotherapy (S.K.), Freiburg Brain Imaging, University Clinic Freiburg, Germany; Wellcome Trust Centre for Neuroimaging (S.K., C.C., G.C.T., B.D., J.A., R.S.J.F.) and Department of Clinical Neurology (S.J.T.), Institute of Neurology, University College London, UK; Department of Psychiatry (H.J., J.S.P.), The University of Iowa, Iowa City, IA; Max Planck Institute for Biological Cybernetics (W.K.), Tübingen, Germany; Département d'études cognitives (R.S.J.F.), Ecole Normale Supérieure, Paris, France; and Laboratory of Neuroimaging (R.S.J.F.), IRCCS Santa Lucia, Rome, Italy.
Address correspondence and reprint requests to Dr. Stefan Klöppel, Department of Psychiatry, University Clinic Freiburg, Hauptstr. 5, Freiburg, Germany stefan.kloeppel{at}uniklinik-freiburg.de
Background: Treatment of neurodegenerative diseases is likely to be most beneficial in the very early, possibly preclinical stages of degeneration. We explored the usefulness of fully automatic structural MRI classification methods for detecting subtle degenerative change. The availability of a definitive genetic test for Huntington disease (HD) provides an excellent metric for judging the performance of such methods in gene mutation carriers who are free of symptoms.
Methods: Using the gray matter segment of MRI scans, this study explored the usefulness of a multivariate support vector machine to automatically identify presymptomatic HD gene mutation carriers (PSCs) in the absence of any a priori information. A multicenter data set of 96 PSCs and 95 age- and sex-matched controls was studied. The PSC group was subclassified into three groups based on time from predicted clinical onset, an estimate that is a function of DNA mutation size and age.
Results: Subjects with at least a 33% chance of developing unequivocal signs of HD in 5 years were correctly assigned to the PSC group 69% of the time. Accuracy improved to 83% when regions affected by the disease were selected a priori for analysis. Performance was at chance when the probability of developing symptoms in 5 years was less than 10%.
Conclusions: Presymptomatic Huntington disease gene mutation carriers close to estimated diagnostic onset were successfully separated from controls on the basis of single anatomic scans, without additional a priori information. Prior information is required to allow separation when degenerative changes are either subtle or variable.
Abbreviations: AD = Alzheimer disease; CI = confidence interval; DWI = diffusion-weighted imaging; FWE = family-wise error; HD = Huntington disease; PSC = presymptomatic Huntington disease gene mutation carrier; ROI = region of interest; SVM = support vector machine; VBM = voxel-based morphometry.
Supplemental data at www.neurology.org.
*See appendix e-1 on the Neurology® Web site for a list of the participating centers and researchers collecting scans.
This work was supported by the Wellcome Trust (grant 075696 2/04/2 to R.S.J.F., J.A., and S.J.T.). The PREDICT-HD study is supported by grants from the NIH (NS 40068) and the High Q Foundation to the principal investigator, J.S.P.
Disclosure: The authors report no disclosures.
Received May 9, 2008. Accepted in final form October 23, 2008.
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