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

• DOI: 10.21203/rs.2.19511/v4
• Publication Date: 2020-05-04T18:32:06Z
• Authors: Guri Hagberg; Hege Ihle-Hansen; Brynjar Fure; Bente Thommessen; Håkon Ihle-Hansen; Anne Rita Øksengård; Mona K. Beyer; Wyller; Ebba Gløersen Müller; Sarah T. Pendlebury; Per Selnes
• Keywords: Male; 0301 basic medicine; Positron emission tomography; Amyloid; 610; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Humans; Cognitive Dysfunction; Benzothiazoles; RC346-429; Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Amyloidosis; Middle Aged; Prognosis; Magnetic Resonance Imaging; 3. Good health; Stroke; Cognitive impairment; Cerebrospinal fluid; Positron-Emission Tomography; Dementia; Female; Neurology. Diseases of the nervous system; Atrophy; Biomarkers; Research Article; Follow-Up Studies

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 seven years correlates with amyloid-β peptide (Aβ₄₂) levels in cerebrospinal fluid (CSF) at one year, and with measures of neurodegeneration and cognition at seven 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 seven 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 one year. Thirteen out of 26 patients were diagnosed with CI seven years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ₄₂ levels at one year, MTA grade, GCA scale, MMSE score or TMT-A at seven 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 seven 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.