Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Amyloid deposition, hypometabolism, and longitudinal cognitive decline
Article first published online: 29 OCT 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 4, pages 578–586, October 2012
How to Cite
Landau, S. M., Mintun, M. A., Joshi, A. D., Koeppe, R. A., Petersen, R. C., Aisen, P. S., Weiner, M. W., Jagust, W. J. and for the Alzheimer's Disease Neuroimaging Initiative (2012), Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol., 72: 578–586. doi: 10.1002/ana.23650
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Accepted manuscript online: 24 MAY 2012 04:57AM EST
- Manuscript Accepted: 16 MAY 2012
- Manuscript Revised: 8 MAY 2012
- Manuscript Received: 29 MAR 2012
- Alzheimer's Disease Neuroimaging Initiative
- ADNI; National Institutes of Health. Grant Number: U01 AG024904
- ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering
- Abbott; Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Amorfix Life Sciences Ltd.
- Bayer HealthCare
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals Inc.
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd.
- Genentech, Inc.
- GE Healthcare
- Innogenetics, N.V.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc.
- Merck & Co., Inc.
- Meso Scale Diagnostics, LLC.
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Synarc, Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research is providing funds
- ADNI clinical sites in Canada
- Foundation for the National Institutes of Health
- Northern California Institute for Research and Education
- Alzheimer's Disease Cooperative Study at the University of California, San Diego
- ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles
- NIH. Grant Numbers: P30AG010129, K01 AG030514, U01 AG024904
- Dana Foundation
Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements.
We examined associations between mean cortical florbetapir uptake, mean 18F-fluorodeoxyglucose–positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements.
Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir.
Although both hypometabolism and β-amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline. ANN NEUROL 2012;72:578–586