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Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer’s disease and recent evidence for genetic risk factors specifically related to posterio...

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Autores principales: Firth, Nicholas C, Primativo, Silvia, Marinescu, Razvan-Valentin, Shakespeare, Timothy J, Suarez-Gonzalez, Aida, Lehmann, Manja, Carton, Amelia, Ocal, Dilek, Pavisic, Ivanna, Paterson, Ross W, Slattery, Catherine F, Foulkes, Alexander J M, Ridha, Basil H, Gil-Néciga, Eulogio, Oxtoby, Neil P, Young, Alexandra L, Modat, Marc, Cardoso, M Jorge, Ourselin, Sebastien, Ryan, Natalie S, Miller, Bruce L, Rabinovici, Gil D, Warrington, Elizabeth K, Rossor, Martin N, Fox, Nick C, Warren, Jason D, Alexander, Daniel C, Schott, Jonathan M, Yong, Keir X X, Crutch, Sebastian J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598737/
https://www.ncbi.nlm.nih.gov/pubmed/31219516
http://dx.doi.org/10.1093/brain/awz136
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author Firth, Nicholas C
Primativo, Silvia
Marinescu, Razvan-Valentin
Shakespeare, Timothy J
Suarez-Gonzalez, Aida
Lehmann, Manja
Carton, Amelia
Ocal, Dilek
Pavisic, Ivanna
Paterson, Ross W
Slattery, Catherine F
Foulkes, Alexander J M
Ridha, Basil H
Gil-Néciga, Eulogio
Oxtoby, Neil P
Young, Alexandra L
Modat, Marc
Cardoso, M Jorge
Ourselin, Sebastien
Ryan, Natalie S
Miller, Bruce L
Rabinovici, Gil D
Warrington, Elizabeth K
Rossor, Martin N
Fox, Nick C
Warren, Jason D
Alexander, Daniel C
Schott, Jonathan M
Yong, Keir X X
Crutch, Sebastian J
author_facet Firth, Nicholas C
Primativo, Silvia
Marinescu, Razvan-Valentin
Shakespeare, Timothy J
Suarez-Gonzalez, Aida
Lehmann, Manja
Carton, Amelia
Ocal, Dilek
Pavisic, Ivanna
Paterson, Ross W
Slattery, Catherine F
Foulkes, Alexander J M
Ridha, Basil H
Gil-Néciga, Eulogio
Oxtoby, Neil P
Young, Alexandra L
Modat, Marc
Cardoso, M Jorge
Ourselin, Sebastien
Ryan, Natalie S
Miller, Bruce L
Rabinovici, Gil D
Warrington, Elizabeth K
Rossor, Martin N
Fox, Nick C
Warren, Jason D
Alexander, Daniel C
Schott, Jonathan M
Yong, Keir X X
Crutch, Sebastian J
author_sort Firth, Nicholas C
collection PubMed
description Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer’s disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer’s disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer’s disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer’s disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer’s disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer’s disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer’s disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer’s disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer’s disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer’s disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.
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spelling pubmed-65987372019-07-03 Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy Firth, Nicholas C Primativo, Silvia Marinescu, Razvan-Valentin Shakespeare, Timothy J Suarez-Gonzalez, Aida Lehmann, Manja Carton, Amelia Ocal, Dilek Pavisic, Ivanna Paterson, Ross W Slattery, Catherine F Foulkes, Alexander J M Ridha, Basil H Gil-Néciga, Eulogio Oxtoby, Neil P Young, Alexandra L Modat, Marc Cardoso, M Jorge Ourselin, Sebastien Ryan, Natalie S Miller, Bruce L Rabinovici, Gil D Warrington, Elizabeth K Rossor, Martin N Fox, Nick C Warren, Jason D Alexander, Daniel C Schott, Jonathan M Yong, Keir X X Crutch, Sebastian J Brain Original Articles Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer’s disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer’s disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer’s disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer’s disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer’s disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer’s disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer’s disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer’s disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer’s disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer’s disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy. Oxford University Press 2019-07 2019-06-20 /pmc/articles/PMC6598737/ /pubmed/31219516 http://dx.doi.org/10.1093/brain/awz136 Text en © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Firth, Nicholas C
Primativo, Silvia
Marinescu, Razvan-Valentin
Shakespeare, Timothy J
Suarez-Gonzalez, Aida
Lehmann, Manja
Carton, Amelia
Ocal, Dilek
Pavisic, Ivanna
Paterson, Ross W
Slattery, Catherine F
Foulkes, Alexander J M
Ridha, Basil H
Gil-Néciga, Eulogio
Oxtoby, Neil P
Young, Alexandra L
Modat, Marc
Cardoso, M Jorge
Ourselin, Sebastien
Ryan, Natalie S
Miller, Bruce L
Rabinovici, Gil D
Warrington, Elizabeth K
Rossor, Martin N
Fox, Nick C
Warren, Jason D
Alexander, Daniel C
Schott, Jonathan M
Yong, Keir X X
Crutch, Sebastian J
Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title_full Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title_fullStr Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title_full_unstemmed Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title_short Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
title_sort longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598737/
https://www.ncbi.nlm.nih.gov/pubmed/31219516
http://dx.doi.org/10.1093/brain/awz136
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