Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art

Abstract

Introduction: Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also the ability to minimize the potentially hazardous off-target effects.

Areas covered: This review covers the role of intranasal insulin therapy for cognitive impairment and neurodegeneration, particularly AD. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The review provides evidence that brain insulin resistance is an important and early abnormality in AD, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy.

Expert opinion: Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy and specificity of intranasal insulin therapy.

Keywords::

• Alzheimer's disease
• diabetes mellitus
• insulin-like growth factor
• insulin resistance, insulin sensitizers
• intranasal insulin
• mild cognitive impairment
• obesity
• peroxisome proliferator-activated receptor agonists

Declaration of interest

This paper was sponsored by AA-11431 and AA-12908 from the National Institutes of Health.

Notes

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