title: Intracranial Arterial 4D-Flow is Associated with Metrics of Brain Health and Alzheimer's Disease.
abstract: BACKGROUND
  While cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used 4D-Flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the Circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile.
  
  
  METHODS
  312 patients along the AD continuum (172 middle-aged, 60 cognitively-healthy older, 44 mild cognitive impairment (MCI), and 36 AD) underwent MRI, CSF, and medical examinations. Regression was used to predict CSF biomarkers and atrophy from 4D-Flow, and ANCOVA to compare vascular health between groups.
  
  
  RESULTS
  Decreased mean flow in the middle cerebral (MCA) and superior portion of the internal carotid arteries (sICA) and increased pulsatility in the MCA were associated with greater brain atrophy. Decreased mean flow in the sICA was associated with lower Aβ-42 in the CSF, a pathological biomarker profile associated with AD. Interestingly, although metrics of flow and pulsatility differed markedly across the AD spectrum, there were no significant differences in cardiovascular risk score, mean arterial pressure and pulse pressure across the three age-matched older cohorts.
  
  
  CONCLUSIONS
  By measuring intracranial arterial health directly with 4D-Flow MRI, these data suggest that intracranial arterial health is compromised in symptomatic AD. Even after accounting for disease stage, cerebral artery health is associated with atrophy and an AD Aβ-42 profile, suggesting neurovascular health may contribute to the etiopathogenesis of AD.
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53705 ; Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53705.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Berman
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Rivera-Rivera
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719.
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Clark
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53705.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Racine
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison WI 53792.
authors.forename: Jon G
authors.initials: JG
authors.lastname: Keevil
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; School of Nursing, University of Wisconsin-Madison, Madison, WI 53705.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Bratzke
authors.affiliation: Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison WI 53705 ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison WI 53705 ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.affiliation: Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Department of Molecular Neuroscience, University College London, Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison WI 53705 ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
authors.forename: Patrick
authors.initials: P
authors.lastname: Turski
authors.affiliation: Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison WI 53705 ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719 ; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI 53705.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705 ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wieben
keywords: Alzheimer’s disease; Circle of Willis; cardiovascular risk; mean blood flow; pulsatility index