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Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. METHOD...

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Autores principales: Bos, Isabelle, Verhey, Frans R., Ramakers, Inez H.G.B., Jacobs, Heidi I. L., Soininen, Hilkka, Freund-Levi, Yvonne, Hampel, Harald, Tsolaki, Magda, Wallin, Åsa K., van Buchem, Mark A., Oleksik, Ania, Verbeek, Marcel M., Olde Rikkert, Marcel, van der Flier, Wiesje M., Scheltens, Philip, Aalten, Pauline, Visser, Pieter Jelle, Vos, Stephanie J. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747152/
https://www.ncbi.nlm.nih.gov/pubmed/29284531
http://dx.doi.org/10.1186/s13195-017-0328-9
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author Bos, Isabelle
Verhey, Frans R.
Ramakers, Inez H.G.B.
Jacobs, Heidi I. L.
Soininen, Hilkka
Freund-Levi, Yvonne
Hampel, Harald
Tsolaki, Magda
Wallin, Åsa K.
van Buchem, Mark A.
Oleksik, Ania
Verbeek, Marcel M.
Olde Rikkert, Marcel
van der Flier, Wiesje M.
Scheltens, Philip
Aalten, Pauline
Visser, Pieter Jelle
Vos, Stephanie J. B.
author_facet Bos, Isabelle
Verhey, Frans R.
Ramakers, Inez H.G.B.
Jacobs, Heidi I. L.
Soininen, Hilkka
Freund-Levi, Yvonne
Hampel, Harald
Tsolaki, Magda
Wallin, Åsa K.
van Buchem, Mark A.
Oleksik, Ania
Verbeek, Marcel M.
Olde Rikkert, Marcel
van der Flier, Wiesje M.
Scheltens, Philip
Aalten, Pauline
Visser, Pieter Jelle
Vos, Stephanie J. B.
author_sort Bos, Isabelle
collection PubMed
description BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ(1–42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (−) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. RESULTS: MTA and t-tau were elevated in the Aβ − WMH+, Aβ + WMH−, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-017-0328-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-57471522018-01-03 Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline Bos, Isabelle Verhey, Frans R. Ramakers, Inez H.G.B. Jacobs, Heidi I. L. Soininen, Hilkka Freund-Levi, Yvonne Hampel, Harald Tsolaki, Magda Wallin, Åsa K. van Buchem, Mark A. Oleksik, Ania Verbeek, Marcel M. Olde Rikkert, Marcel van der Flier, Wiesje M. Scheltens, Philip Aalten, Pauline Visser, Pieter Jelle Vos, Stephanie J. B. Alzheimers Res Ther Research BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ(1–42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (−) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. RESULTS: MTA and t-tau were elevated in the Aβ − WMH+, Aβ + WMH−, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-017-0328-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-29 /pmc/articles/PMC5747152/ /pubmed/29284531 http://dx.doi.org/10.1186/s13195-017-0328-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bos, Isabelle
Verhey, Frans R.
Ramakers, Inez H.G.B.
Jacobs, Heidi I. L.
Soininen, Hilkka
Freund-Levi, Yvonne
Hampel, Harald
Tsolaki, Magda
Wallin, Åsa K.
van Buchem, Mark A.
Oleksik, Ania
Verbeek, Marcel M.
Olde Rikkert, Marcel
van der Flier, Wiesje M.
Scheltens, Philip
Aalten, Pauline
Visser, Pieter Jelle
Vos, Stephanie J. B.
Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title_full Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title_fullStr Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title_full_unstemmed Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title_short Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
title_sort cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747152/
https://www.ncbi.nlm.nih.gov/pubmed/29284531
http://dx.doi.org/10.1186/s13195-017-0328-9
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