title: Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.
abstract: Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood-brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer's patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer's disease (p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden sara.shams@ki.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Shams
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Granberg
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Martola
authors.affiliation: Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mana
authors.initials: M
authors.lastname: Shams
authors.affiliation: Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Seyed-Mohammad
authors.initials: SM
authors.lastname: Fereshtehnejad
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Cavallin
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Aspelin
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Kristoffersen-Wiberg
authors.affiliation: Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D005260:Female; D006470:Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; cerebral microbleeds; cerebrospinal fluid biomarkers; dementia; magnetic resonance imaging