Distinct clinical and metabolic deficits in
PCA and AD are not related to amyloid
M.H. Rosenbloom, MD
A. Alkalay, MD
S.L. Baker, PhD
J.P. O’Neil, PhD
M. Janabi, PhD
I.V. Yen, BA
M. Growdon, BA
J. Jang, BA
C. Madison, MA
E.C. Mormino, BS
H.J. Rosen, MD
M.W. Weiner, MD
B.L. Miller, MD
W.J. Jagust, MD
G.D. Rabinovici, MD
Background/Objective: Patients with posterior cortical atrophy (PCA) often have Alzheimer dis-
ease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD.
using Pittsburgh compound B (PiB) and FDG-PET.
Methods: Patients with PCA (n ? 12, age 57.5 ? 7.4, Mini-Mental State Examination [MMSE]
22.2 ? 5.1), AD (n ? 14, age 58.8 ? 9.6, MMSE 23.8 ? 6.7), and cognitively normal controls
(NC, n ? 30, age 73.6 ? 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution
volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a
voxel-wise basis and by comparing binding in regions of interest (ROIs).
throughout frontal, temporoparietal, and occipital cortex (p ? 0.0001). There were no regional
differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns
in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in
temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hy-
pometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p ?
0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA.
Conclusions: Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypo-
metabolism extends more posteriorly into occipital cortex. Further studies are needed to deter-
mine the mechanisms of selective network degeneration in focal variants of AD. Neurology®2011;
AD ? Alzheimer disease; DVR ? distribution volume ratio; FWE ? family-wise error; LPA ? logopenic aphasia; MMSE ?
Mini-Mental State Examination; MNI ? Montreal Neurological Institute; NC ? normal control; NFT ? neurofibrillary tangle(s);
PCA ? posterior cortical atrophy; PiB ? Pittsburgh compound B; PPA ? primary progressive aphasia; ROI ? region of
interest; VBM ? voxel-based morphometry; VOSP ? Visual Object and Space Perception battery.
Posterior cortical atrophy (PCA) is a focal neurodegenerative disorder of higher visual process-
ing and spatial praxis with relative sparing of memory and insight.1At autopsy, the majority of
patients are found to have underlying Alzheimer disease (AD) as the causative pathology.1-3
The distribution of AD pathology in PCA is controversial, with some studies demonstrating
higher numbers of amyloid plaques in primary and association visual cortex in PCA compared
to typical AD4,5and others showing no difference in the distribution of A? pathology.2,3
Postmortem comparisons are limited in that they study the end stages of disease, which makes
relating changes seen at autopsy to in vivo disease evolution difficult.
Fibrillar A? pathology can be measured during life using PET with [11C]-labeled Pittsburgh
compound B (PiB-PET).6PiB binding during life correlates strongly with distribution and
e-Pub ahead of print on April 27, 2011, at www.neurology.org.
From the Memory and Aging Center and Department of Neurology (M.H.R., A.A., M.G., J.J., H.J.R., M.L.G.-T., B.L.M., W.J.J., G.D.R.),
University of California San Francisco, San Francisco; Helen Wills Neuroscience Institute (A.A., N.A., C.M., E.C.M., W.J.J., G.D.R.), University of
California Berkeley, Berkeley; Lawrence Berkeley National Laboratory (S.L.B., J.P.O., M.J., I.V.Y., W.J.J., G.D.R.), Berkeley; and Center for Imaging
of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA.
Study funding: Supported by the NIH/NIA K23-AG031861, R01-AG027859, P01-AG1972403, P50 AG023501, Alzheimer’s Association NIRG-07-
59422, ZEN-08-87090, John Douglas French Alzheimer’s Foundation, and State of California DHS-ADRC 04-33516.
Disclosure: Author disclosures are provided at the end of the article.
Address correspondence and
reprint requests to Dr. Michael
HealthPartner Specialty Center,
Center for Dementia and
Alzheimer’s Care, 401 Phalen
Boulevard, Mail Stop: 41104C,
St. Paul, MN 55130
Copyright © 2011 by AAN Enterprises, Inc.
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