4.7 Article

PET staging of amyloidosis using striatum

Journal

ALZHEIMERS & DEMENTIA
Volume 14, Issue 10, Pages 1281-1292

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2018.04.011

Keywords

Amyloid PET imaging; Structural MRI; Striatum; Cortex; Cognitive aging; MCI; Alzheimer's disease; Classification; Staging

Funding

  1. ADNI (NIH) [U01 AG024904]
  2. DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
  3. National Institute on Aging NIH/NIA
  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 Ltd.
  14. Eisai Inc.
  15. Elan Pharmaceuticals, Inc.
  16. Eli Lilly and Company
  17. Euroimmun
  18. F. Hoffmann-La Roche Ltd.
  19. Canadian Institutes of Health Research
  20. NIH/NIA [P01AG036694, R01AG046396]
  21. Harvard NeuroDiscovery Center
  22. Fidelity Biosciences
  23. Belgian National Science Foundation (FNRS) [SPD28094292]
  24. Belgian Foundation for Alzheimer Research (SAO-FRA) [P16008]
  25. Genentech, Inc.
  26. Fujirebio
  27. GE Healthcare
  28. IXICO Ltd.
  29. Janssen Alzheimer Immunotherapy Research & Development, LLC
  30. Johnson & Johnson Pharmaceutical Research and Development LLC
  31. Lumosity
  32. Lundbeck
  33. Merck Co., Inc.
  34. Meso Scale Diagnostics, LLC
  35. NeuroRx Research
  36. Neurotrack Technologies
  37. Novartis Pharmaceuticals Corporation
  38. Pfizer Inc.
  39. Piramal Imaging
  40. Servier
  41. Takeda Pharmaceutical Company
  42. Transition Therapeutics
  43. NATIONAL INSTITUTE ON AGING [P01AG036694, U01AG024904, K24AG035007, R01AG046396] Funding Source: NIH RePORTER

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Introduction: Amyloid positron emission tomography (PET) data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. Methods: We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. Results: Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. Discussion: PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

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