Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution
Abstract
Background/Objective:
Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo 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).
Results:
Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake 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 hypometabolism 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 hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.
Get full access to this article
View all available purchase options and get full access to this article.
Supplementary Material
File (appendix_e-1_table_e-1_table_e-2.docx)
- Download
- 49.21 KB
REFERENCES
1.
Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer's disease. Brain 2007;130:2636–2645.
2.
Tang-Wai DF, Graff-Radford NR, Boeve BF, et al. Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology 2004;63:1168–1174.
3.
Renner JA, Burns JM, Hou CE, McKeel DW, Storandt M, Morris JC. Progressive posterior cortical dysfunction: a clinicopathologic series. Neurology 2004;63:1175–1180.
4.
von Gunten A, Bouras C, Kovari E, Giannakopoulos P, Hof PR. Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease. Brain Res Rev 2006;51:176–211.
5.
Hof PR, Vogt BA, Bouras C, Morrison JH. Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways. Vision Res 1997;37:3609–3625.
6.
Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol Mar 2004;55:306–319.
7.
Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 2008;131:1630–1645.
8.
Bacskai BJ, Frosch MP, Freeman SH, et al. Molecular imaging with Pittsburgh compound B confirmed at autopsy: a case report. Arch Neurol 2007;64:431–434.
9.
Tenovuo O, Kemppainen N, Aalto S, Nagren K, Rinne JO. Posterior cortical atrophy: a rare form of dementia with in vivo evidence of amyloid-beta accumulation. J Alzheimers Dis 2008;15:351–355.
10.
Ng SY, Villemagne VL, Masters CL, Rowe CC. Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh compound B. Arch Neurol 2007;64:1140–1144.
11.
Kambe T, Motoi Y, Ishii K, Hattori N. Posterior cortical atrophy with [C] Pittsburgh compound B accumulation in the primary visual cortex. J Neurol Epub 2009 Nov 14.
12.
Edison P, Archer HA, Hinz R, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PiB and [18F]FDG PET study. Neurology 2007;68:501–508.
13.
Kemppainen NM, Aalto S, Wilson IA, et al. Voxel-based analysis of PET amyloid ligand [11C]PiB uptake in Alzheimer disease. Neurology 2006;67:1575–1580.
14.
Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008;64:388–401.
15.
Rabinovici GD, Furst AJ, Alkalay A, et al. Increased metabolic vulnerability in early-onset Alzheimer's disease is not related to amyloid burden. Brain 2010;133:512–528.
16.
Kramer JH, Jurik J, Sha SJ, et al. Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease. Cogn Behav Neurol 2003;16:211–218.
17.
Warrington EK, James M. The Visual Object and Space Perception Battery. Bury St Edmunds: Thames Valley Test Company; 1991.
18.
Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test, second ed. San Antonio, TX: The Psychological Corporation; 2000.
19.
McMonagle P, Deering F, Berliner Y, Kertesz A. The cognitive profile of posterior cortical atrophy. Neurology 2006;66:331–338.
20.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939–944.
21.
Mormino EC, Kluth JT, Madison CM, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 2009;132:1310–1323.
22.
Rabinovici GD, Furst AJ, O'Neil JP, et al. 11C-PiB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007;68:1205–1212.
23.
Lopresti BJ, Klunk WE, Mathis CA, et al. Simplified quantification of Pittsburgh compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med 2005;46:1959–1972.
24.
Price JC, Klunk WE, Lopresti BJ, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 2005;25:1528–1547.
25.
Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 1995;19:541–547.
26.
Whitwell JL, Jack CR, Kantarci K, et al. Imaging correlates of posterior cortical atrophy. Neurobiol Aging 2007;28:1051–1061.
27.
Meltzer CC, Leal JP, Mayberg HS, Wagner HN, Frost JJ. Correction of PET data for partial volume effects in human cerebral cortex by MR imaging. J Comput Assist Tomogr 1990;14:561–570.
28.
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 2002;15:273–289.
29.
Whitwell JL, Weigand SD, Shiung MM, et al. Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease. Brain 2007;130:708–719.
30.
Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004;55:335–346.
31.
Migliaccio R, Agosta F, Rascovsky K, et al. Clinical syndromes associated with posterior atrophy: early age at onset AD spectrum. Neurology 2009;73:1571–1578.
32.
Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008;63:709–719.
33.
Buckner RL, Sepulcre J, Talukdar T, et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. J Neurosci 2009;29:1860–1873.
34.
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009;62:42–52.
35.
Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 2005;25:7709–7717.
36.
Rogalski E, Johnson N, Weintraub S, Mesulam M. Increased frequency of learning disability in patients with primary progressive aphasia and their first-degree relatives. Arch Neurol 2008;65:244–248.
37.
Mucke L, Masliah E, Yu GQ, et al. High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000;20:4050–4058.
38.
Walsh DM, Selkoe DJ. A beta oligomers: a decade of discovery. J Neurochem 2007;101:1172–1184.
39.
Kim EJ, Cho SS, Jeong Y, et al. Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. Brain 2005;128:1790–1801.
40.
Frisoni GB, Pievani M, Testa C, et al. The topography of grey matter involvement in early and late onset Alzheimer's disease. Brain 2007;130:720–730.
Information & Authors
Information
Published In
Copyright
Copyright © 2011 by AAN Enterprises, Inc.
Publication History
Received: August 9, 2010
Accepted: November 23, 2010
Published online: April 27, 2011
Published in print: May 24, 2011
Disclosure
Dr. Rosenbloom, A. Alkalay, N. Agarwal, and Dr. Baker report no disclosures. Dr. O'Neill receives research support from Genzyme Corporation, the US Department of Energy, the US Army Medical Research & Materiel Command, and the NIH. Dr. Janabi receives research support from the NIH. I.V. Yen, M. Growdon, J. Jang, C. Madson, and E.C. Mormino report no disclosures. Dr. Rosen serves on a scientific advisory board for Avanir Pharmaceuticals; receives publishing royalties for The Emotional Brain (Oxford University Press); and receives research support from the NIH (NIA, NINDS, DHS/ADP/ARCC) and the Larry L. Hillblom Foundation. Dr. Gorno-Tempini receives research support from the NIH (NINDS, NIA), the John Douglas French Alzheimer's Foundation, the Alzheimer's Association, the Larry L. Hillblom Foundation, the Koret Family Foundation, and the McBean Family Foundation. Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly and Company, CoMentis, Inc., Neurochem Inc, Eisai Inc., Avid Radiopharmaceuticals Inc., Aegis Therapies, Genentech, Inc., Allergan, Inc., Lippincott Williams & Wilkins, Bristol-Myers Squibb, Forest Laboratories, Inc., Pfizer Inc, McKinsey & Company, Mitsubishi Tanabe Pharma Corporation, and Novartis; has received funding for travel from Nestlé and Kenes International and to attend conferences not funded by industry; serves on the editorial board of Alzheimer's & Dementia; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan Corporation; receives research support from Merck & Co., Radiopharmaceuticals Inc., the NIH, the Veterans Administration, and the State of California; and holds stock in Synarc and Elan Corporation. Dr. Miller serves on a scientific advisory board for the Alzheimer's Disease Clinical Study; serves as an Editor for Neurocase and as an Associate Editor of ADAD; receives royalties from the publication of Behavioral Neurology of Dementia (Cambridge, 2009), Handbook of Neurology (Elsevier, 2009), and The Human Frontal Lobes (Guilford, 2008); serves as a consultant for Lundbeck Inc., Elan Corporation, and Allon Therapeutics, Inc.; serves on speakers' bureaus for Novartis and Pfizer Inc.; and receives research support from Novartis and the NIH/NIA and the State of California Alzheimer's Center. Dr. Jagust has served on a scientific advisory board for Genentech, Inc.; serves as Associate Editor for Frontiers in Human Neuroscience and on the editorial boards of Annals of Neurology, Brain Imaging and Behavior, and Alzheimer's Disease and Associated Disorders; receives publishing royalties for Imaging the Aging Brain (Oxford University Press, 2009); has served as a consultant for Synarc, Elan Corporation/Janssen Alzheimer Immunotherapy, Genentech, Inc., Abbott, GE Healthcare, Ceregene, Bayer Schering Pharma, Schering-Plough Corp., TauRx Pharmaceuticals, Otsuka Pharmaceutical Co., Ltd., and Merck & Co; and receives research support from the NIH and from the Alzheimer's Association. Dr. Rabinovici serves on scientific advisory boards for Novartis and GE Healthcare and receives research support from the NIH/NIA, the Alzheimer's Association, and the John Douglas French Alzheimer's Foundation.
Authors
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Clinical and imaging clues to posterior cortical atrophy, Neurology Clinical Practice, 5, 3, (270-271), (2023)./doi/10.1212/CPJ.0000000000000136
- Posterior cortical atrophy: clinical, neuroimaging, and neuropathological features, Expert Review of Neurotherapeutics, 23, 3, (227-236), (2023).https://doi.org/10.1080/14737175.2023.2190885
- Neuroimaging Biomarkers in Alzheimer’s Disease and Related Disorders, Biomarkers in Neuropsychiatry, (163-188), (2023).https://doi.org/10.1007/978-3-031-43356-6_11
- Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease, Frontiers in Neuroscience, 16, (2022).https://doi.org/10.3389/fnins.2022.899612
- The temporal lobe in typical and atypical Alzheimer disease, The Temporal Lobe, (449-466), (2022).https://doi.org/10.1016/B978-0-12-823493-8.00004-3
- Validity of cingulate–precuneus–temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer’s Disease, Journal of Neurology, 269, 8, (4440-4451), (2022).https://doi.org/10.1007/s00415-022-11086-y
- Bridging Scales in Alzheimer's Disease: Biological Framework for Brain Simulation With The Virtual Brain, Frontiers in Neuroinformatics, 15, (2021).https://doi.org/10.3389/fninf.2021.630172
- A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms, Psychogeriatrics, 21, 3, (396-406), (2021).https://doi.org/10.1111/psyg.12665
- Graph Models of Pathology Spread in Alzheimer's Disease: An Alternative to Conventional Graph Theoretic Analysis, Brain Connectivity, 11, 10, (799-814), (2021).https://doi.org/10.1089/brain.2020.0905
- Alzheimer’s Disease, Imaging Dementia, (1-30), (2021).https://doi.org/10.1007/978-3-030-66773-3_1
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.