title: Intranasal insulin enhanced resting-state functional connectivity of hippocampal regions in type 2 diabetes.
abstract: Type 2 diabetes mellitus (T2DM) alters brain function and manifests as brain atrophy. Intranasal insulin has emerged as a promising intervention for treatment of cognitive impairment. We evaluated the acute effects of intranasal insulin on resting-state brain functional connectivity in older adults with T2DM. This proof-of-concept, randomized, double-blind, placebo-controlled study evaluated the effects of a single 40 IU dose of insulin or saline in 14 diabetic and 14 control subjects. Resting-state functional connectivity between the hippocampal region and default mode network (DMN) was quantified using functional MRI (fMRI) at 3Tesla. Following insulin administration, diabetic patients demonstrated increased resting-state connectivity between the hippocampal regions and the medial frontal cortex (MFC) as compared with placebo (cluster size: right, P = 0.03) and other DMN regions. On placebo, the diabetes group had lower connectivity between the hippocampal region and the MFC as compared with control subjects (cluster size: right, P = 0.02), but on insulin, MFC connectivity was similar to control subjects. Resting-state connectivity correlated with cognitive performance. A single dose of intranasal insulin increases resting-state functional connectivity between the hippocampal regions and multiple DMN regions in older adults with T2DM. Intranasal insulin administration may modify functional connectivity among brain regions regulating memory and complex cognitive behaviors.
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Manor
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Peter
authors.initials: P
authors.lastname: Novak
authors.affiliation: New England Geriatric Research Education and Clinical Center-Boston Division, VA Boston Healthcare, and Department of Psychiatry, Harvard Medical School, Boston, MA.
authors.forename: William
authors.initials: W
authors.lastname: Milberg
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China College of Engineering, Peking University, Beijing, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China College of Engineering, Peking University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA vnovak@bidmc.harvard.edu.
authors.forename: Vera
authors.initials: V
authors.lastname: Novak
mesh_terms: D000281:Administration, Intranasal; D000368:Aged; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin