4.5 Article

Detecting biological heterogeneity patterns in ADNI amnestic mild cognitive impairment based on volumetric MRI

Journal

BRAIN IMAGING AND BEHAVIOR
Volume 14, Issue 5, Pages 1792-1804

Publisher

SPRINGER
DOI: 10.1007/s11682-019-00115-6

Keywords

Latent class analysis; Volumetric MRI; Cognitive function; Amnestic MCI; Alzheimer's disease

Categories

Funding

  1. Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
  2. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  3. National Institute on Aging
  4. National Institute of Biomedical Imaging and Bioengineering
  5. AbbVie
  6. Alzheimer's Association
  7. Alzheimer's Drug Discovery Foundation
  8. Araclon Biotech
  9. BioClinica, Inc.
  10. Biogen
  11. Bristol-Myers Squibb Company
  12. CereSpir, Inc.
  13. Cogstate
  14. Eisai Inc.
  15. Elan Pharmaceuticals, Inc.
  16. Eli Lilly and Company
  17. EuroImmun
  18. F. Hoffmann-La Roche Ltd.
  19. company Genentech, Inc.
  20. Fujirebio
  21. GE Healthcare
  22. IXICO Ltd.
  23. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  24. Johnson & Johnson Pharmaceutical Research & Development LLC.
  25. Lumosity
  26. Lundbeck
  27. Merck Co., Inc.
  28. Meso Scale Diagnostics, LLC.
  29. NeuroRx Research
  30. Neurotrack Technologies
  31. Novartis Pharmaceuticals Corporation
  32. Pfizer Inc.
  33. Piramal Imaging
  34. Servier
  35. Takeda Pharmaceutical Company
  36. Transition Therapeutics
  37. Canadian Institutes of Health Research
  38. National Institutes of Health [NIA 2 P01 AG03949, NIA 1R01AG039409-01, NIA R03 AG045474, NIH K01AG054700]
  39. Leonard and Sylvia Marx Foundation
  40. Czap Foundation

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There is substantial biological heterogeneity among older adults with amnestic mild cognitive impairment (aMCI). We hypothesized that this heterogeneity can be detected solely based on volumetric MRI measures, which potentially have clinical implications and can improve our ability to predict clinical outcomes. We used latent class analysis (LCA) to identify subgroups among persons with aMCI (n = 696) enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), based on baseline volumetric MRI measures. We used volumetric measures of 10 different brain regions. The subgroups were validated with respect to demographics, cognitive performance, and other AD biomarkers. The subgroups were compared with each other and with normal and Alzheimer's disease (AD) groups with respect to baseline cognitive function and longitudinal rate of conversion. Four aMCI subgroups emerged with distinct MRI patterns: The first subgroup (n = 404), most similar to normal controls in volumetric characteristics and cognitive function, had the lowest incidence of AD. The second subgroup (n = 230) had the most similar MRI profile to early AD, along with poor performance in memory and executive function domains. The third subgroup (n = 36) had the highest global atrophy, very small hippocampus and worst overall cognitive performance. The fourth subgroup (n = 26) had the least amount of atrophy, however still had poor cognitive function specifically in in the executive function domain. Individuals with aMCI who were clinically categorized within one group other showed substantial heterogeneity based on MRI volumetric measures.

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