title: Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults.
abstract: Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife.
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Hoscheidt
authors.affiliation: 2 Department of Kinesiology, University of Wisconsin, Madison, WI, USA.
authors.forename: J Mikhail
authors.initials: JM
authors.lastname: Kellawan
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Berman
authors.affiliation: 3 Department of Medical Physics, University of Wisconsin, Madison, WI, USA.|4 Department of Radiology, University of Wisconsin, Madison, WI, USA.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Rivera-Rivera
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Krause
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Oh
authors.affiliation: 5 The Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel.|6 The Icahn School of Medicine, Mount Sinai, NY, USA.
authors.forename: Michal S
authors.initials: MS
authors.lastname: Beeri
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|4 Department of Radiology, University of Wisconsin, Madison, WI, USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.affiliation: 3 Department of Medical Physics, University of Wisconsin, Madison, WI, USA.|4 Department of Radiology, University of Wisconsin, Madison, WI, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wieben
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|7 Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|8 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|7 Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|8 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|7 Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|8 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: 2 Department of Kinesiology, University of Wisconsin, Madison, WI, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Schrage
authors.affiliation: 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|8 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity / Q000502:physiology; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D003287:Contrast Media; D003704:Dementia / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010477:Perfusion
chemical_list: D003287:Contrast Media
keywords: Alzheimer’s; arterial spin labeling; cerebral blood flow; cerebrovascular disease; diabetes