title: Cerebral microbleeds topography and cerebrospinal fluid biomarkers in cognitive impairment.
abstract: Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid β(Aβ)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Aβ42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer's disease ( P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem ( P < 0.001). There were tendencies for increased Aβ42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds ( P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes ( P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Aβ42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities ( P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Shams
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Granberg
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Martola
authors.affiliation: 3 Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Charidimou
authors.affiliation: 4 Department of Neurobiology, Care Sciences and Society, H1, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.|5 Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mana
authors.initials: M
authors.lastname: Shams
authors.affiliation: 4 Department of Neurobiology, Care Sciences and Society, H1, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.|5 Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Seyed-Mohammad
authors.initials: SM
authors.lastname: Fereshtehnejad
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Cavallin
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Aspelin
authors.affiliation: 1 Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden.|2 Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wiberg-Kristoffersen
authors.affiliation: 4 Department of Neurobiology, Care Sciences and Society, H1, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.|5 Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
mesh_terms: D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology*; D015331:Cohort Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008569:Memory Disorders / Q000150:complications / Q000473:pathology*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
keywords: Amyloid angiopathy; cerebrospinal fluid biomarkers; cognitive impairment; intracerebral hemorrhage; magnetic resonance imaging