title: Effect of intranasally administered insulin on cerebral blood flow and perfusion; a randomized experiment in young and older adults.
abstract: Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68.28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults.
authors.affiliation: Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Abimbola A
authors.initials: AA
authors.lastname: Akintola
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: van Opstal
authors.affiliation: Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands.|Department of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark.
authors.forename: Rudi G
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands.|Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands.|Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000367:Age Factors; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: aging; cerebral blood flow; continuous arterial spin labelling (CASL); intranasal insulin; magnetic resonance imaging (MRI); phase contrast MR angiography