Consensus classification of posterior cortical atrophy
Open accessAbstract
Introduction: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web‐based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results: A three‐level classification framework for PCA is described comprising both syndrome‐ and disease‐level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico‐radiological syndrome. Classification level 2 (PCA‐pure, PCA‐plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA‐AD], Lewy body disease [PCA‐LBD], corticobasal degeneration [PCA‐CBD], prion disease [PCA‐prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome‐level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion: There was strong agreement regarding the definition of the core clinico‐radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single‐center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
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Cortical blindness in posterior cortical atrophy is distinct from avoidable vision impairment, usually due to AD, but often initially misdiagnosed as ocular disease.
“This is distinct from cortical blindness seen in posterior cortical atrophy, usually due to AD, but often initially misdiagnosed as ocular disease.(250)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [250]
The Introduction describes PCA as visual dysfunction arising from degeneration of posterior cortical regions, and §4.3 says AD is overwhelmingly its most common underlying cause. Section 4.1 distinguishes PCA visual complaints from symptoms explained by significant primary ocular disease, but the copy does not say PCA is often initially misdiagnosed as ocular disease. Section 7 describes primary visual failure as a rare PCA variant, so it does not support treating cortical blindness as the usual PCA presentation. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn PCA, the neurodegenerative process is known to follow an occipito-parietal to temporal lobe progression.
“Further, in PCA the neurodegenerative process is known to follow an occipito-parietal to temporal lobe progression”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [5]
The Introduction (page unavailable) describes early neurodegeneration of posterior cortical regions and later, more diffuse cognitive dysfunction. The PCA stages section (page unavailable) also describes later impairments in memory and language. Neither passage establishes that degeneration follows a specific occipito-parietal-to-temporal-lobe sequence; the Heterogeneity section describes biparietal and occipitotemporal variants, not successive stages. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSpecific clinical phenotypes commonly associated with Alzheimer's disease pathology are the amnestic syndrome of the hippocampal type, posterior cortical atrophy variant, and logopenic variant primary progressive aphasia.
“Specific clinical phenotype commonly associated with Alzheimer’s disease pathology (common Alzheimer’s disease phenotypes) are: the amnestic syndrome of the hippocampal type91 (typical), the posterior cortical atrophy variant,92 and the logopenic variant primary progressive aphasia93,94 (appendix p 2).”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [92]
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“phenotypes) are: the amnestic syndrome of the hippocampal type 66 (typical), the posterior cortical atrophy variant 67 , and the logopenic variant primary progressive aphasia 68,69 (Supplementary Figure 1).”
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Self-citationSepulveda-Falla, D., Sanchez, J. S., Almeida, M. C., Boassa, D., Acosta-Uribe, J., Vila-Castelar, C., Ramirez-Gomez, L., Baena, A., Aguillon, D., Villalba-Moreno, N. D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02467-8 · Cited by 92 · see citing works
“Further, in PCA the neurodegenerative process is known to follow an occipito-parietal to temporal lobe progression, and in the E280A APOE3ch case we observed a relative sparing of parietal and frontal cortices (Supp.”
BackgroundMethodInfluentialStaffaroni, A., Elahi, F., McDermott, D., Marton, K., Karageorgiou, E., Sacco, S., Paoletti, M., Caverzasi, E., Hess, C., Rosen, H., et al. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1608808 · Cited by 91 · see citing works
Young, C. B., Winer, J. R., Younes, K., Cody, K. A., Betthauser, T. J., Johnson, S. C., Schultz, A., Sperling, R. A., Greicius, M. D., Cobos, I., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.0676 · Cited by 79 · see citing works
Self-citationNeocortical origin and progression of gray matter atrophy in nonamnestic Alzheimer's disease
Phillips, J. S., Da Re, F., Dratch, L., Xie, S. X., Irwin, D. J., McMillan, C. T., Vaishnavi, S. N., Ferrarese, C., Lee, E. B., Shaw, L. M., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.11.008 · Cited by 74 · see citing works
Diagnosis and Management of Posterior Cortical Atrophy
Yong, K. X. X., Graff-Radford, J., Ahmed, S., Chapleau, M., Ossenkoppele, R., Putcha, D., Rabinovici, G. D., Suarez-Gonzalez, A., Schott, J. M., Crutch, S., et al. (2023) · Current Treatment Options in Neurology · doi:10.1007/s11940-022-00745-0 · Cited by 51 · see citing works
Self-citationVisuospatial dysfunction in Alzheimer's disease and behavioural variant frontotemporal dementia
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Atypical Alzheimer Disease Variants
Polsinelli, A. J., & Apostolova, L. G. (2022) · Continuum · doi:10.1212/con.0000000000001082 · Cited by 39 · see citing works
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- Authors
- Crutch, S. J., Schott, J. M., Rabinovici, G. D., Murray, M., Snowden, J. S., van der Flier, W. M., Dickerson, B. C., Vandenberghe, R., Ahmed, S., Bak, T. H., Boeve, B. F., Butler, C., Cappa, S. F., Ceccaldi, M., de Souza, L. C., Dubois, B., Felician, O., Galasko, D., Graff‐Radford, J., Graff‐Radford, N. R., Hof, P. R., Krolak‐Salmon, P., Lehmann, M., Magnin, E., Mendez, M. F., Nestor, P. J., Onyike, C. U., Pelak, V. S., Pijnenburg, Y., Primativo, S., Rossor, M. N., Ryan, N. S., Scheltens, P., Shakespeare, T. J., Suárez González, A., Tang‐Wai, D. F., Yong, K. X. X., Carrillo, M., Fox, N. C., & Alzheimer's Association ISTAART Atypical Alzheimer's Disease and Associated Syndromes Professional Interest Area
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- University of California, San Francisco (US)
- Mayo Clinic (US)
- Salford Royal NHS Foundation Trust (GB)
- Department of Neurology VU University Medical Centre, Amsterdam Neuroscience Amsterdam The Netherlands
- Harvard University (US)
- KU Leuven (BE)
- University of Oxford (GB)
- University of Edinburgh (GB)
- Vita-Salute San Raffaele University (IT)
- Inserm (FR)
- Departamento de Clínica Médica, Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil
- Pitié-Salpêtrière Hospital (FR)
- Aix‐Marseille Université, INSERM, Institut de Neurosciences des Systèmes Marseille France
- University of California San Diego (US)
- Icahn School of Medicine at Mount Sinai (US)
- Centre National de la Recherche Scientifique (FR)
- Department of Neurology Regional Memory Centre (CMRR), CHU Besançon Besançon France
- University of California, Los Angeles (US)
- German Center for Neurodegenerative Diseases (DE)
- Johns Hopkins University (US)
- University of Colorado Anschutz (US)
- Amsterdam Neuroscience (NL)
- Dementia Research Centre UCL Institute of Neurology London UK
- University Health Network (CA)
- Medical and Scientific Relations Alzheimer's Association Chicago IL USA
- Corresponding author
- Crutch, Sebastian J.
- ORCID
- Crutch, Sebastian J.
- Schott, Jonathan M.
- Rabinovici, Gil D.
- Murray, Melissa
- Snowden, Julie S.
- Dickerson, Bradford C.
- Vandenberghe, Rik
- Ahmed, Samrah
- Bak, Thomas H.
- Boeve, Bradley F.
- Butler, Christopher
- Cappa, Stefano F.
- Ceccaldi, Mathieu
- Dubois, Bruno
- Galasko, Douglas
- Graff‐Radford, Jonathan
- Graff‐Radford, Neill R.
- Hof, Patrick R.
- Krolak‐Salmon, Pierre
- Lehmann, Manja
- Mendez, Mario F.
- Nestor, Peter J.
- Onyike, Chiadi U.
- Pelak, Victoria S.
- Pijnenburg, Yolande
- Primativo, Silvia
- Rossor, Martin N.
- Ryan, Natalie S.
- Scheltens, Philip
- Shakespeare, Timothy J.
- Tang‐Wai, David F.
- Yong, Keir X.X.
- Fox, Nick C.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2017-03
- Volume
- 13
- Issue
- 8
- Pages
- 870-884
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5788455
- OpenAlex
- W2592378632
- Cited by
- 665
- References
- 66
- Citations by year
- 2026: 61 · 2025: 82 · 2024: 88 · 2023: 85 · 2022: 82 · 2021: 78 · 2020: 67 · 2019: 61 · 2018: 42 · 2017: 17
- FWCI
- 42.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by)
- PubMed Central (acceptedVersion, cc-by)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DZNE Pub (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Alzheimer's Association
- Economic and Social Research Council
- Engineering and Physical Sciences Research Council (EP/M006093/1, EP/J020990/1)
- Alzheimer’s Research UK (ARUK‐RF2013‐5)
- Brain Research Trust (UCC14191)
- American College of Radiology
- Alzheimer Nederland
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- posterior cortical atrophy, classification framework
- MeSH terms
- Brain, Brain Diseases, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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