Amyloid imaging in mild cognitive impairment subtypes†
Corresponding Author
David A. Wolk MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Penn Memory Center, 3615 Chestnut Street, Suite 212, Philadelphia, PA 19104Search for more papers by this authorJulie C. Price PhD
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorJudy A. Saxton PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorBeth E. Snitz PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorJeffrey A. James BS
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorOscar L. Lopez MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorHoward J. Aizenstein MD, PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorAnn D. Cohen PhD
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorLisa A. Weissfeld PhD
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorChester A. Mathis PhD
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorWilliam E. Klunk MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorSteven T. DeKosky MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorCorresponding Author
David A. Wolk MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Penn Memory Center, 3615 Chestnut Street, Suite 212, Philadelphia, PA 19104Search for more papers by this authorJulie C. Price PhD
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorJudy A. Saxton PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorBeth E. Snitz PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorJeffrey A. James BS
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorOscar L. Lopez MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorHoward J. Aizenstein MD, PhD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorAnn D. Cohen PhD
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorLisa A. Weissfeld PhD
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorChester A. Mathis PhD
Department of Radiology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorWilliam E. Klunk MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorSteven T. DeKosky MD
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
Department of Neurology, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorPotential 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.
Abstract
Objective
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.
Methods
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.
Results
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.”
Interpretation
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
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