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

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 i...
Ausführliche Beschreibung

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 ($ Aβ_{42} $) 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 $ Aβ_{42} $ 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 $ Aβ_{42} $ 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. Ausführliche Beschreibung

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

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Stroke Cognitive impairment Cerebrospinal fluid Positron emission tomography Prognosis

Übergeordnetes Werk:	Enthalten in: BMC neurology - London : BioMed Central, 2001, 20(2020), 1 vom: 08. Mai
Übergeordnetes Werk:	volume:20 ; year:2020 ; number:1 ; day:08 ; month:05

Links:	Volltext

DOI / URN:	10.1186/s12883-020-01753-w

Katalog-ID:	SPR039661261