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BMC Neurology
Published in: BMC Neurology 1/2020

01-12-2020 | Magnetic Resonance Imaging | Research article

No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study

Authors: Guri Hagberg, Hege Ihle-Hansen, Brynjar Fure, Bente Thommessen, Håkon Ihle-Hansen, Anne Rita Øksengård, Mona K. Beyer, Torgeir B. Wyller, Ebba Gløersen Müller, Sarah T. Pendlebury, Per Selnes

Published in: BMC Neurology | Issue 1/2020

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Abstract

Background

Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-β peptide (Aβ42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke.

Methods

208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ42 levels were assessed using linear regression.

Results

In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort.

Conclusions

Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke.

Trial registration

Clinicaltrials.​gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.
Appendix
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Metadata
Title
No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study
Authors
Guri Hagberg
Hege Ihle-Hansen
Brynjar Fure
Bente Thommessen
Håkon Ihle-Hansen
Anne Rita Øksengård
Mona K. Beyer
Torgeir B. Wyller
Ebba Gløersen Müller
Sarah T. Pendlebury
Per Selnes
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-020-01753-w

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