No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke: a seven-year follow-up studyShow others and affiliations
2020 (English)In: BMC Neurology, E-ISSN 1471-2377, Vol. 20, no 1, article id 174
Article in journal (Refereed) Published
Abstract [en]
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 (F-18-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed F-18-Flut-PET uptake after 7 years correlates with amyloid-beta peptide (A beta(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 F-18-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between F-18-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 A beta(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 A beta(42) levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with F-18-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.
Place, publisher, year, edition, pages
BioMed Central, 2020. Vol. 20, no 1, article id 174
Keywords [en]
Cerebrospinal fluid, Cognitive impairment, Positron emission tomography, Prognosis, Stroke
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-81769DOI: 10.1186/s12883-020-01753-wISI: 000533413400001PubMedID: 32384876Scopus ID: 2-s2.0-85084720970OAI: oai:DiVA.org:oru-81769DiVA, id: diva2:1429748
2020-05-122020-05-122022-02-10Bibliographically approved