Intranasal Insulin for Alzheimer’s Disease

Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer’s disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathwa...

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Veröffentlicht in:	CNS drugs Jg. 35; H. 1; S. 21 - 37
1. Verfasser:	Hallschmid, Manfred
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Cham Springer International Publishing 01.01.2021 Springer Nature B.V
Schlagworte:	Administration, Intranasal Alzheimer Disease - drug therapy Alzheimer Disease - physiopathology Alzheimer's disease Animals Brain - drug effects Brain - physiopathology Central nervous system Clinical trials Cognition & reasoning Cognitive ability Cognitive Dysfunction - drug therapy Cognitive Dysfunction - physiopathology Female Humans Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - pharmacology Hypothalamus Insulin Insulin - administration & dosage Insulin - pharmacology Insulin Resistance Male Medicine Medicine & Public Health Memory Memory - drug effects Neurodegenerative diseases Neurology Neurosciences Parkinson's disease Pharmacotherapy Pituitary Psychiatry Psychopharmacology Review Review Article Sex differences Sex Factors Sleep Synaptic plasticity United States > US
ISSN:	1172-7047, 1179-1934, 1179-1934
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Abstract	Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer’s disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer’s disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer’s disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer’s disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer’s disease.
AbstractList	Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer's disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer's disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer's disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer's disease. Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer's disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer's disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer's disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer's disease.Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer's disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer's disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer's disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer's disease.
Author	Hallschmid, Manfred
Author_xml	– sequence: 1 givenname: Manfred orcidid: 0000-0002-0352-1106 surname: Hallschmid fullname: Hallschmid, Manfred email: manfred.hallschmid@uni-tuebingen.de organization: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, German Center for Diabetes Research (DZD), Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen
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Snippet	Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer’s... Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's...
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SubjectTerms	Administration, Intranasal Alzheimer Disease - drug therapy Alzheimer Disease - physiopathology Alzheimer's disease Animals Brain - drug effects Brain - physiopathology Central nervous system Clinical trials Cognition & reasoning Cognitive ability Cognitive Dysfunction - drug therapy Cognitive Dysfunction - physiopathology Female Humans Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - pharmacology Hypothalamus Insulin Insulin - administration & dosage Insulin - pharmacology Insulin Resistance Male Medicine Medicine & Public Health Memory Memory - drug effects Neurodegenerative diseases Neurology Neurosciences Parkinson's disease Pharmacotherapy Pituitary Psychiatry Psychopharmacology Review Review Article Sex differences Sex Factors Sleep Synaptic plasticity
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Title	Intranasal Insulin for Alzheimer’s Disease
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