4.5 Article

Applying Automated MR-Based Diagnostic Methods to the Memory Clinic: A Prospective Study

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 47, Issue 4, Pages 939-954

Publisher

IOS PRESS
DOI: 10.3233/JAD-150334

Keywords

Dementia diagnostics; machine learning; magnetic resonance imaging; prognosis; support vector machine

Categories

Funding

  1. Deutsche Forschungsgemeinschaft [KL 2415/2-1]
  2. Federal Ministry for Economic Affairs and Energy [KF3223201LW3]
  3. German Consortium for Frontotemporal Lobar Degeneration - German Federal Ministry of Education and Research
  4. Parkinson's disease Foundation [PDF-IRG-1307]
  5. Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
  6. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  7. National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
  8. Alzheimer's Association
  9. Alzheimer's Drug Discovery Foundation
  10. Araclon Biotech
  11. Bio-Clinica, Inc.
  12. Biogen Idec Inc.
  13. Bristol-Myers Squibb Company
  14. Eisai Inc.
  15. Elan Pharmaceuticals, Inc.
  16. Eli Lilly and Company
  17. EuroImmun
  18. F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.
  19. Fujirebio
  20. GE Healthcare
  21. IXICO Ltd.
  22. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  23. Johnson & Johnson Pharmaceutical Research & Development LLC.
  24. Medpace, Inc.
  25. Merck Co., Inc.
  26. Meso Scale Diagnostics, LLC.
  27. NeuroRx Research
  28. Neurotrack Technologies
  29. Novartis Pharmaceuticals Corporation
  30. Pfizer Inc.
  31. Piramal Imaging
  32. Servier
  33. Synarc Inc.
  34. Takeda Pharmaceutical Company
  35. Canadian Institutes of Health Research
  36. Northern California Institute for Research and Education
  37. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [TL1TR000096] Funding Source: NIH RePORTER
  38. NATIONAL INSTITUTE ON AGING [U01AG024904, P50AG005134, P30AG013846] Funding Source: NIH RePORTER

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Several studies have demonstrated that fully automated pattern recognition methods applied to structural magnetic resonance imaging (MRI) aid in the diagnosis of dementia, but these conclusions are based on highly preselected samples that significantly differ from that seen in a dementia clinic. At a single dementia clinic, we evaluated the ability of a linear support vector machine trained with completely unrelated data to differentiate between Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia, and healthy aging based on 3D-T1 weighted MRI data sets. Furthermore, we predicted progression to AD in subjects with mild cognitive impairment (MCI) at baseline and automatically quantified white matter hyperintensities from FLAIR-images. Separating additionally recruited healthy elderly from those with dementia was accurate with an area under the curve (AUC) of 0.97 (according to Fig. 4). Multi-class separation of patients with either AD or FTD from other included groups was good on the training set (AUC > 0.9) but substantially less accurate (AUC=0.76 for AD, AUC=0.78 for FTD) on 134 cases from the local clinic. Longitudinal data from 28 cases with MCI at baseline and appropriate follow-up data were available. The computer tool discriminated progressive from stable MCI with AUC=0.73, compared to AUC=0.80 for the training set. A relatively low accuracy by clinicians (AUC=0.81) illustrates the difficulties of predicting conversion in this heterogeneous cohort. This first application of a MRI-based pattern recognition method to a routine sample demonstrates feasibility, but also illustrates that automated multi-class differential diagnoses have to be the focus of future methodological developments and application studies.

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