The regions of the brain such as the hippocampus and the frontal cortex are densely populated with insulin receptors.  As well they are found in synapses in which insulin signaling participates in synaptic remodeling and synaptogenesis (1,2). In parallel insulin regulates the utilization of glucose in the hippocampus and other regions of the brain to promote optimal memory in normal metabolism (3).  In AD, it has been shown that reduced levels of insulin and insulin activity exist (4,5).  Interestingly insulin has a tight relationship to amyloid beta, a toxic peptide responsible for the onset of the disease.  Insulin can regulate the levels of amyloid beta to deliver protection from the degenerative nature of the peptide on neurons (6-8).

A pilot clinical trial published in the archives of neurology titled,  Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment, has shown insulin’ ability to be a protective new therapy in the fight against AD.  The trial hosted 104 participants, of which 30 participated in the use of a placebo, while insulin at 20IU and 40IU were delivered to 36 and 38 participants respectively.  The insulin was administered through a nasal drug delivery device for a total of 4 months. Surprisingly the 20IU and 40IU group experienced improved memory recall and preserved general cognition.

It was very important to identify a method of administration of insulin properly and direct to the brain without disrupting blood sugar levels.  When taken as a nasal spray it reaches the brain in just a few minutes with no apparent adverse affects on the body. Although a very promising study, it is still a preliminary study, more research will have to be carried out to ensure the safety and effectiveness of insulin as a therapy for longterm use against AD.

1. Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008;58(5):708-719. PUBMED
2. Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim Biophys Acta. 2009;1792(5):482-496. PUBMED
3. McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Sherwin RS. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem. 2010;93(4):546-553. PUBMED
4. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998;50(1):164-168. FREE FULL TEXT
5. Steen E, Terry BM, Rivera EJ; et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis. 2005;7(1):63-80. PUBMED
6. De Felice FG, Vieira MN, Bomfim TR; et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009;106(6):1971-1976. FREE FULL TEXT
7. Gasparini L, Gouras GK, Wang R; et al. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001;21(8):2561-2570. FREE FULL TEXT
8. Lee CC, Kuo YM, Huang CC, Hsu KS. Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging. 2009;30(3):377-387. PUBMED

In April 2008, Nature published results of an informal online survey of readers’ use of cognition-enhancing drugs, namely Ritalin, Provigil, and beta-blockers. As we all know, online polls are notoriously slippery, but the results are nonetheless illuminating. One in five respondents claimed to have used had “used drugs for non-medical reasons to stimulate their focus, concentration or memory.” Furthermore, 80% of respondents felt that healthy adults should be able to take these drugs as a matter of personal choice, while 69% were willing to risk mild side effects to take such drugs.

A recent article by Magaret Talbot in the Guardian newspaper echoes these findings, pointing out that neuroenhancers (smart drugs) are endemic in college campuses throughout the United States. Talbot highlights a 2002 study from Cambridge University where 30 volunteers were given Modafinil (originally developed to treat narcolepsy) and then tested on a battery of cognitive tests. The  group performed better on several important measures of cognitive ability relative to controls, leading to the conclusion that “Modafinil offers significant potential as a cognitive enhancer”. Recent studies of drugs developed to treat ADHD and Alzheimer’s have produced similar results. In short, not only are people taking the drugs, they are are also benefiting from it.

So if these drugs work, why are we not all taking them? Well, for one thing we still don’t know much about the long-term impact – but this is a criticism that can be aimed at every new medication. This issue aside, the idea of taking cognitive enhancers strikes me as unsettling. The prospect of taking drugs even when we are not sick seems to stem from the white collar obsession with productivity. In many respects, it speaks of desperation – to wring out the last drops of perspiration from an over-taxed mind. I don’t see a promise of inspiration, but rather the depressing proposition of grinding efficiency. If life is about finding a balance, neuroenhancers seem to tilt the scales in an unhealthy direction.