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


METHODS
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.


CONCLUSIONS
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.
Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Departments of Pathology (Neuropathology), Neurology, and Neurosurgery , Pierre Galletti Research Building, Claverick Street, Room 419, Providence, RI 02903 , USA +1 401 444 7364 ; +1 401 444 2939 ; Suzanne_DeLaMonte_MD@Brown.edu.
Suzanne M
SM
de la Monte
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007333:Insulin Resistance / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin