Intranasal insulin treatment might boost cognition in people with mild cognitive impairment

Meta-analysis of 29 studies across multiple disorders.


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Since the brain was long believed to be an insulin-insensitive organ, most insulin research for decades has concentrated chiefly on the action of insulin in peripheral tissues. It has been demonstrated that central insulin delivery significantly impacts controlling cognition. This may be accomplished by influencing long-term potentiation and long-term depression processes through insulin signaling pathways or by causing the release of numerous neurotrophic substances to aid in the survival of neurons.

According to some theories, several metabolic and cognitive problems have been linked to abnormal brain insulin signaling. Intranasal insulin (INI) is a non-invasive method that limits peripheral side effects while enabling analysis and manipulation of insulin signaling in the brain.

A recent investigation examined how INI affected patients from various patient categories and healthy people. They show that INI may have pro-cognitive advantages for combined global cognition in AD and MCI patients.

No statistically significant effect was seen for each of the cognitive subdomains. INI administration over a longer period of time might provide additional therapeutic advantages over administration in the short term. This is the first review to combine data from populations of healthy people and patient groups, offering valuable early evidence for this new and developing subject.

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standard and methodology, researchers did a systematic review and meta-analysis. On July 22, 2021, a review procedure was transmitted to the PROSPERO international prospectively registered systematic database. The initial investigation was carried out between 2000 and July 2021.

All identified publications from the systematic search were reviewed by three authors independently; inclusion or exclusion of a study needed consent from at least two authors. Any discrepancies were settled by conversation and a second look at the source materials.

The Cochrane Risk of Bias (RoB) tool was used to assess bias in the context of our outcomes of interest. Seven evidence-based domains were assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.

The primary outcome was the effect of INI on cognition as assessed by individual cognitive domains. A measure of global cognition was calculated by averaging the effect sizes of all individual cognitive domains for each study. The effect size for global cognition for each study was then entered into another meta-analysis to obtain a pooled effect of global cognition across studies for each patient population.

The number of individual cognitive domains varied per study.

Our initial search identified 2654 results. Following title and abstract screening, 52 studies were assessed for full-text eligibility. A total of 32 studies met the inclusion criteria for this review, and 26 of these studies, with 1,726 patients and healthy individuals.

Twenty-nine studies in healthy individuals and those with Alzheimer’s disease (AD)/mild cognitive impairment (MCI), mental health disorders, and 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.

No significant effects of INI were found for global cognition among studies with healthy individuals and other patient populations.

Journal Reference:

  1. Wu S, Stogios N, Hahn M, Navagnanavel J, Emami Z, Chintoh A, et al. (2023) Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and Meta-analysis. PLoS ONE 18(6): e0286887. DOI: 10.1371/journal.pone.0286887