title: Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study.
abstract: Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Aβ in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared with controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal, and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark. Electronic address: seskildsen@cfin.au.dk.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Eskildsen
authors.affiliation: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Gyldensted
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Kartheeban
authors.initials: K
authors.lastname: Nagenthiraja
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Rune B
authors.initials: RB
authors.lastname: Nielsen
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Mikkel Bo
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Rikke B
authors.initials: RB
authors.lastname: Dalby
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Frandsen
authors.affiliation: Department of Nuclear Medicine, PET-Center, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Rodell
authors.affiliation: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Gyldensted
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Sune N
authors.initials: SN
authors.lastname: Jespersen
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Torben E
authors.initials: TE
authors.lastname: Lund
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Mouridsen
authors.affiliation: Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Brændgaard
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark; Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Østergaard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology*; D001783:Blood Flow Velocity; D002196:Capillaries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D013997:Time Factors; D066127:White Matter / Q000098:blood supply* / Q000000981:diagnostic imaging
keywords: Alzheimer; Capillary transit-time heterogeneity (CTH); MRI; Oxygen extraction fraction (OEF); Perfusion; White matter hyperintensities