Potential conflict of interest: GE Healthcare holds a license agreement with the University of Pittsburgh based on the technology described in this manuscript. Drs. Klunk and Mathis are co-inventors of PiB and, as such, have a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this manuscript. All other authors have no conflicts of interest with this work and had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Amyloid imaging in mild cognitive impairment subtypes†
Article first published online: 18 MAR 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 65, Issue 5, pages 557–568, May 2009
How to Cite
Wolk, D. A., Price, J. C., Saxton, J. A., Snitz, B. E., James, J. A., Lopez, O. L., Aizenstein, H. J., Cohen, A. D., Weissfeld, L. A., Mathis, C. A., Klunk, W. E. and DeKosky, S. T. (2009), Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol., 65: 557–568. doi: 10.1002/ana.21598
- Issue published online: 11 JUN 2009
- Article first published online: 18 MAR 2009
- Accepted manuscript online: 18 MAR 2009 12:00AM EST
- Manuscript Accepted: 31 OCT 2008
- Manuscript Revised: 26 SEP 2008
- Manuscript Received: 22 JUL 2008
- National Institute of Aging. Grant Numbers: K02 AG001039, K02 AG027998, K23 AG028018, R01 AG018402, R01 AG020098, R01 AG020226, R37 AG025516, P01 AG025204, P50 AG005133
- National Institute of Mental Health. Grant Number: R01 MH070729
- Alzheimer's Association. Grant Number: TLL-01-3381
- US Department of Energy. Grant Number: DE-FD02-03 ER63590
- Dana Foundation
We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome.
Twenty-six patients with MCI (13 single-domain amnestic-MCI [a-MCI], 6 multidomain a-MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty-three had clinical follow-up (21.2 ± 16.0 [standard deviation] months) subsequent to their PiB scan.
Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered “amyloid-positive.” All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 single-domain a-MCI, 5/6 multidomain a-MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow-up demonstrated 5 of 13 amyloid-positive patients, but 0 of 10 amyloid-negative patients, converted to clinical AD. Further, 3 of 10 amyloid-negative patients “reverted to normal.”
These data support the notion that amyloid-positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD. Ann Neurol 2009;65:557–568