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Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

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

Authors: Isabelle Bos, Frans R. Verhey, Inez H.G.B. Ramakers, Heidi I. L. Jacobs, Hilkka Soininen, Yvonne Freund-Levi, Harald Hampel, Magda Tsolaki, Åsa K. Wallin, Mark A. van Buchem, Ania Oleksik, Marcel M. Verbeek, Marcel Olde Rikkert, Wiesje M. van der Flier, Philip Scheltens, Pauline Aalten, Pieter Jelle Visser, Stephanie J. B. Vos

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

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 Aβ1–42 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.
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Metadata
Title
Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
Authors
Isabelle Bos
Frans R. Verhey
Inez H.G.B. Ramakers
Heidi I. L. Jacobs
Hilkka Soininen
Yvonne Freund-Levi
Harald Hampel
Magda Tsolaki
Åsa K. Wallin
Mark A. van Buchem
Ania Oleksik
Marcel M. Verbeek
Marcel Olde Rikkert
Wiesje M. van der Flier
Philip Scheltens
Pauline Aalten
Pieter Jelle Visser
Stephanie J. B. Vos
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0328-9

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