Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and meta-analysis

Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation and modulation of insulin signaling in the brain while limiting peripheral side effects. The objectiv...

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Published in:	PloS one Vol. 18; no. 6; p. e0286887
Main Authors:	Wu, Sally, Stogios, Nicolette, Hahn, Margaret, Navagnanavel, Janani, Emami, Zahra, Chintoh, Araba, Gerretsen, Philip, Graff-Guerrero, Ariel, Rajji, Tarek K, Remington, Gary, Agarwal, Sri Mahavir
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 28-06-2023 Public Library of Science (PLoS)
Subjects:	Alzheimer Disease - complications Alzheimer Disease - drug therapy Alzheimer's disease Alzheimers disease Analysis Bias Biology and Life Sciences Brain Clinical trials Cognition Cognition & reasoning Cognition Disorders - etiology Cognitive ability Cognitive Dysfunction - complications Dementia Development and progression Diabetes Glucose Health aspects Humans Insulin Insulin - therapeutic use Insulin lispro Insulin resistance Medical research Medicine and Health Sciences Medicine, Experimental Memory Meta-analysis Metabolic disorders Metabolism Neurodegenerative diseases Parkinson's disease Parkinsons disease Patients Physical Sciences Physiology Populations Research and Analysis Methods Schizophrenia Side effects Systematic review Type 2 diabetes Web portals Canada
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Summary:	Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation and modulation of insulin signaling in the brain while limiting peripheral side effects. The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals. MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data. Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition. This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 Competing Interests: The authors have read the journal’s policy and have the following competing interests: S.W. is supported by the Ontario Graduate Scholarship (OGS) and the Cleghorn Fellowship in Schizophrenia Studies outside of the submitted work. N.S. is supported by the Ontario Graduate Scholarship (OGS) and Banting and Best Diabetes Centre (BBDC) Novo-Nordisk Graduate Studentship outside of the submitted work. M.H. is supported in part by an Academic Scholars Award from the Department of Psychiatry, University of Toronto, and has grant support from the Banting and Best Diabetes Centre (BBDC), the Canadian Institutes of Health Research (CIHR), PSI Foundation, Ontario, holds the Kelly and Michael Meighen Chair in Psychosis Prevention, and the Cardy Schizophrenia Research Chair outside of the submitted work. She is also supported by the Danish Diabetes Academy, and a Steno Diabetes Centre Fellowship Award outside of the submitted work. T.K.R. has received research support from Brain Canada, Brain and Behavior Research Foundation, Bright Focus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute outside of the submitted work. G.R. has received research support from the Canadian Institutes of Health Research (CIHR), University of Toronto, Research Hospital Fund–Canada Foundation for Innovation (RHF-CFI), and HLS Therapeutics Inc. outside of the submitted work. S.M.A. is supported in part by an Academic Scholars Award from the Department of Psychiatry, University of Toronto, and has grant support from CIHR, PSI Foundation, Ontario, and the CAMH Discovery Fund outside of the submitted work. M.H. receives consultant fees from Alkermes Inc. G.R. has received advisory board support from HLS Therapeutics and consultant fees from Mitsubishi Tanabe Pharma Corporation outside of the submitted work. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. SW and NS share first authorship on this work.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0286887