4.7 Article

The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment

Journal

SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-26151-8

Keywords

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Funding

  1. Swedish Foundation for Strategic Research (SSF)
  2. Swedish Research Council (VR)
  3. Swedish Research Council for Health, Working Life and Welfare
  4. Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro)
  5. Stockholm County Council
  6. Karolinska Institutet
  7. Hjarnfonden
  8. Alzheimerfonden
  9. Stiftelsen Olle Engkvist Byggmastare
  10. Ake Wibergs Stiftelse
  11. Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
  12. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  13. National Institute on Aging
  14. National Institute of Biomedical Imaging and Bioengineering
  15. AbbVie
  16. Alzheimer's Association
  17. Alzheimer's Drug Discovery Foundation
  18. Araclon Biotech
  19. BioClinica, Inc.
  20. Biogen
  21. Bristol-Myers Squibb Company
  22. CereSpir, Inc.
  23. Cogstate
  24. Eisai Inc.
  25. Elan Pharmaceuticals, Inc.
  26. Eli Lilly and Company
  27. EuroImmun
  28. F. Hoffmann-La Roche Ltd
  29. Genentech, Inc.
  30. Fujirebio
  31. GE Healthcare
  32. IXICO Ltd
  33. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  34. Johnson & Johnson Pharmaceutical Research & Development LLC.
  35. Lumosity
  36. Lundbeck
  37. Merck Co., Inc.
  38. Meso Scale Diagnostics, LLC.
  39. NeuroRx Research
  40. Neurotrack Technologies
  41. Novartis Pharmaceuticals Corporation
  42. Pfizer Inc.
  43. Piramal Imaging
  44. Servier
  45. Takeda Pharmaceutical Company
  46. Transition Therapeutics
  47. Canadian Institutes of Health Research

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The objective of this study was to evaluate the A/T/N biomarker scheme in relation with brain atrophy patterns in individuals with mild cognitive impairment (MCI). Of the 154 participants with MCI, 74 progressed to AD within 36-months, and 80 remained stable. In addition, 101 cognitively healthy participants and 102 participants with AD were included. The A/T/N classification was assessed with cerebrospinal fluid markers. Each individual was rated as either positive (abnormal) or negative (normal) on each biomarker. Brain atrophy was assessed with visual ratings from magnetic resonance imaging. None of the individuals with MCI progressed to AD if they had a negative A biomarker in conjunction with minimal atrophy. In contrary, several individuals with MCI progressed to AD if they had a positive A biomarker in conjunction with minimal atrophy. Numerous individuals with MCI showed inconsistency in the neurodegeneration domain (N) regarding t-tau and atrophy. The assessment of the A/T/N classification scheme in addition with brain atrophy patterns in MCI, increases the knowledge of the clinical trajectories and the variability within the neurodegeneration domain. This emphasises that individuals with MCI display heterogeneous longitudinal patterns closely connected to their biomarker profiles, which could have important clinical implications.

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