Journal
ALZHEIMERS & DEMENTIA
Volume 14, Issue 10, Pages 1281-1292Publisher
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
Categories
Funding
- ADNI (NIH) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging NIH/NIA
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate Ltd.
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- Euroimmun
- F. Hoffmann-La Roche Ltd.
- Canadian Institutes of Health Research
- NIH/NIA [P01AG036694, R01AG046396]
- Harvard NeuroDiscovery Center
- Fidelity Biosciences
- Belgian National Science Foundation (FNRS) [SPD28094292]
- Belgian Foundation for Alzheimer Research (SAO-FRA) [P16008]
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research and Development LLC
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- 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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