Efficacy of Intranasal Insulin in Improving Cognition in Mild Cognitive Impairment or Dementia: a Systematic Review and Meta-analysis

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2022 Sep 29

PMID 36172480

Authors

Cong Long

Xuke Han

YunJiao Yang

Tongyi Li

Qian Zhou

Qiu Chen

Affiliations

Soon will be listed here.

Abstract

Background: Insulin regulates many aspects of brain function related to mild cognitive impairment (MCI) or dementia, which can be delivered to the brain center via intranasal (IN) devices. Some small, single-site studies indicated that intranasal insulin can enhance memory in patients with MCI or dementia. The pathophysiology of Alzheimer's disease (AD) and diabetes mellitus (DM) overlap, making insulin an attractive therapy for people suffering from MCI or dementia.

Objective: The goal of the study is to evaluate the effectiveness of IN insulin on cognition in patients with MCI or dementia.

Methods: We searched the electronic database for randomized controlled trials (RCTs) that verified the effects of insulin on patients with MCI or dementia.16 studies (899 patients) were identified.

Results: The pooled standard mean difference (SMD) showed no significant difference between IN insulin and placebo groups; however, statistical results suggested a difference between study groups in the effects of ADCS-ADL; AD patients with APOE4 (-) also showed improved performance in verbal memory; other cognitions did not improve significantly.

Conclusion: In view of IN insulin's promising potential, more researches should be conducted at a larger dose after proper selection of insulin types and patients.

Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022353546.

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References

Craft S, Baker L, Montine T, Minoshima S, Watson G, Claxton A . Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2011; 69(1):29-38. PMC: 3260944. DOI: 10.1001/archneurol.2011.233. View

Chapman C, Schioth H, Grillo C, Benedict C . Intranasal insulin in Alzheimer's disease: Food for thought. Neuropharmacology. 2017; 136(Pt B):196-201. PMC: 10523803. DOI: 10.1016/j.neuropharm.2017.11.037. View

Rosenbloom M, Barclay T, Pyle M, Owens B, Cagan A, Anderson C . A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease. CNS Drugs. 2014; 28(12):1185-9. DOI: 10.1007/s40263-014-0214-y. View

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

Reger M, Watson G, Frey 2nd W, Baker L, Cholerton B, Keeling M . Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2005; 27(3):451-8. DOI: 10.1016/j.neurobiolaging.2005.03.016. View

Sasaoka T, Wada T, Tsuneki H . [Insulin resistance and cognitive function]. Nihon Rinsho. 2014; 72(4):633-40. View

Biessels G, Staekenborg S, Brunner E, Brayne C, Scheltens P . Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2005; 5(1):64-74. DOI: 10.1016/S1474-4422(05)70284-2. View

Rosenbloom M, Barclay T, Kashyap B, Hage L, OKeefe L, Svitak A . A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. Drugs Aging. 2021; 38(5):407-415. DOI: 10.1007/s40266-021-00845-7. View

Craft S, Raman R, Chow T, Rafii M, Sun C, Rissman R . Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2020; 77(9):1099-1109. PMC: 7309571. DOI: 10.1001/jamaneurol.2020.1840. View

10.

Lu J, Xu Z . Efficacy of Intranasal Insulin in Improving Cognition in Mild Cognitive Impairment and Alzheimer Disease: A Systematic Review and Meta-analysis. Am J Ther. 2019; 26(6):e756-e762. DOI: 10.1097/MJT.0000000000000926. View

11.

Zhao W, Townsend M . Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochim Biophys Acta. 2008; 1792(5):482-96. DOI: 10.1016/j.bbadis.2008.10.014. View

12.

Hely M, Reid W, Adena M, Halliday G, Morris J . The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008; 23(6):837-44. DOI: 10.1002/mds.21956. View

13.

Gwizdala K, Ferguson D, Kovan J, Novak V, Pontifex M . Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise. Metab Brain Dis. 2021; 36(6):1289-1303. DOI: 10.1007/s11011-021-00727-2. View

14.

Chen Y, Deng Y, Zhang B, Gong C . Deregulation of brain insulin signaling in Alzheimer's disease. Neurosci Bull. 2014; 30(2):282-94. PMC: 5562654. DOI: 10.1007/s12264-013-1408-x. View

15.

Reger M, Watson G, Green P, Wilkinson C, Baker L, Cholerton B . Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2007; 70(6):440-8. DOI: 10.1212/01.WNL.0000265401.62434.36. View

16.

Aarsland D, Creese B, Politis M, Chaudhuri K, Ffytche D, Weintraub D . Cognitive decline in Parkinson disease. Nat Rev Neurol. 2017; 13(4):217-231. PMC: 5643027. DOI: 10.1038/nrneurol.2017.27. View

17.

Novak P, Pimentel Maldonado D, Novak V . Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study. PLoS One. 2019; 14(4):e0214364. PMC: 6483338. DOI: 10.1371/journal.pone.0214364. View

18.

Pontiroli A, Alberetto M, Secchi A, Dossi G, Bosi I, Pozza G . Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. Br Med J (Clin Res Ed). 1982; 284(6312):303-6. PMC: 1495887. DOI: 10.1136/bmj.284.6312.303. View

19.

Kopf D, Frolich L . Risk of incident Alzheimer's disease in diabetic patients: a systematic review of prospective trials. J Alzheimers Dis. 2009; 16(4):677-85. DOI: 10.3233/JAD-2009-1011. View

20.

Cha D, Best M, Bowie C, Gallaugher L, Woldeyohannes H, Soczynska J . A randomized, double-blind, placebo-controlled, crossover trial evaluating the effect of intranasal insulin on cognition and mood in individuals with treatment-resistant major depressive disorder. J Affect Disord. 2016; 210:57-65. DOI: 10.1016/j.jad.2016.12.006. View