Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 12:14:963933.
doi: 10.3389/fnagi.2022.963933. eCollection 2022.

Efficacy of intranasal insulin in improving cognition in mild cognitive impairment or dementia: a systematic review and meta-analysis

Cong Long  1   2 , Xuke Han  1   2 , Yunjiao Yang  1   2 , Tongyi Li  1   2 , Qian Zhou  1   2 , Qiu Chen  1
Affiliations

Efficacy of intranasal insulin in improving cognition in mild cognitive impairment or dementia: a systematic review and meta-analysis

Cong Long et al. Front Aging Neurosci. .

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.

Keywords: MCI (mild cognitive impairment); cognitive; dementia; intranasal insulin; meta-analysis; systematic review.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The flowchart of the study selection process.
Figure 2
Figure 2
Risk of bias summary for each risk of bias item for each included study.
Figure 3
Figure 3
Risk of bias graph authors' judgments about each risk of bias item, presented as a percentage across all induded studies.
Figure 4
Figure 4
Publication bias of studies. (A) Funnel Plot of Standard Error by Std diff in means (Plot observed and imputed); (B) The results of Egger's tests. In this case the intercept (BO) is 0.28494, 95% confidence interval (−0.76470, 1.33458), with t = 0.58223, df = 14. The 1-tailed p-value (recommended) is 0.28483, and the 2-tailed p-value is 0.56967. The results of Egger's tests indicates that there is no publication bias.
Figure 5
Figure 5
Forest plot of pooled standard mean difference (SMD) for combined cognitive score. The pooled SMD was 0.103 [16 studies; 95% confidence interval (CI), −0.05 to 0.25; P = 0.18), showing no significant difference between IN insulin and placebo groups (weights and heterogeneity test are from random-effects model).
Figure 6
Figure 6
Forest plot for the Effects of ADAS-cog (Alzheimer's Disease's Assessment Scale–cognitive subscale). There was no difference between study groups: SMD = 0.15, 95% CI = −0.04 to 0.34; P = 0.12).
Figure 7
Figure 7
Forest plot for the effects of cognitive performance. (A) Forest plot for the effects of the Alzheimer's Disease Cooperative Study–activities of daily living Statistical (ADCS-ADL): results suggested a difference between study groups: (3 studies): SMD = 0.26, 95% CI = 0.05 to 0.47; P = 0.01); (B) Forest plot for the effects of Mini-mental Atate Examination (MMSE): SMD favoured Insulin but not statistically different of the effects (2 studies): SMD = 0.07, 95% CI = −0.50 to 0.64; P = 0.81; (C) Forest plot for the effects of Montreal Cognitive Assessment (MoCA): No differences between study groups of the effects (2 studies): SMD = −0.01, 95% CI = −0.81 to 0.79; P = 0.98; (D) Forest plot for the effects of Unified Parkinson's Disease Rating Scale (UPDRS): There was no difference between study groups (2 studies): SMD = −0.41, 95% CI = −1.00 to 0.18; P = 0.17).
See this image and copyright information in PMC

References

    1. Aarsland D., Creese B., Politis M., Chaudhuri K. R., Ffytche D. H., Weintraub D., et al. . (2017). Cognitive decline in Parkinson disease. Nat. Rev. Neurol. 13, 217–231. 10.1038/nrneurol.2017.27 - DOI - PMC - PubMed
    1. Anonymous (2008). Treatment with intranasal insulin improves memory in early Alzheimer's. disease. China Medical News 23:1
    1. Arnold S. E., Arvanitakis Z., Macauley-Rambach S. L., Koenig A. M., Wang H. Y., Ahima R. S., et al. . (2018). Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat. Rev. Neurol. 14, 168–181. 10.1038/nrneurol.2017.185 - DOI - PMC - PubMed
    1. Bayés M., Rabasseda X., Prous J. R. (2006). Gateways to clinical trials. Methods Find. Exp. Clin. Pharmacol. 28, 719–740. - PubMed
    1. Biessels G. J., Despa F. (2018). Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat. Rev. Endocrinol. 14, 591–604. 10.1038/s41574-018-0048-7 - DOI - PMC - PubMed

Publication types

LinkOut - more resources