Enhancement of Memory in Alzheimer Disease With Insulin and Somatostatin, but Not Glucose

Craft, Suzanne; Asthana, Sanjay; Newcomer, John W.; Wilkinson, Charles W.; Matos, Iris Tio; Baker, Laura D.; Cherrier, Monique M.; Lofgreen, Cassin; Latendresse, Shawn J.; Petrova, Andreana; Plymate, Stephen R.; Raskind, Murray A.; Grimwood, Karla; Veith, Richard C.

doi:10.1001/archpsyc.56.12.1135

Cited by 286 publications

(172 citation statements)

References 50 publications

(28 reference statements)

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…On the background of increasing evidence that Alzheimer's disease (AD) is a neuroendocrine disorder with strikingly reduced CNS expression of genes encoding insulin, IGF-I and IGF-II, as well as the insulin and IGF-I receptors , our finding of improved memory performance after intranasal intake of insulin and its analogs may be of significance for the treatment of memory impairments. This is supported by findings of facilitated recall of verbal memory after intravenous and intranasal treatment with insulin in memory-impaired adults (Craft et al, 1999;Reger et al, 2006). Most recently, also acute effects of intranasal insulin on declarative memory have been reported, demonstrating that recall of previously learned words was enhanced after administration of up to 40 IU of RH-I in patients suffering from AD (Reger et al, 2006).…”

Section: Discussionmentioning

confidence: 56%

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Benedict

Hallschmid

Schmitz

et al. 2006

Neuropsychopharmacol

257

154

View full text Add to dashboard Cite

There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and longterm (4 Â 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (po0.01) and the RH-I groups (po0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (po0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.

show abstract

Section: Discussionmentioning

confidence: 56%

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Benedict

Hallschmid

Schmitz

et al. 2006

Neuropsychopharmacol

257

154

View full text Add to dashboard Cite

show abstract

“…Existing evidence suggests that BDNFTrkB controlled SST-NPY levels may play a critical role in the progression of AD. First, SST-NPY containing interneurons have been implicated in learning and memory [93][94][95][96] and post-mortem brain studies of AD repeatedly observed a severe loss of SST immunoreactive neurons and axons. 31,95,[97][98][99][100] In addition, APPswe/PS1dE9 amyloid plaque producing mice show reduced SST levels in the cortex, 101 and this is likely mediated through the interference of amyloid-beta (Ab) with the BDNF-induced activation of the Ras-mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways.…”

Section: Discussionmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

View full text Add to dashboard Cite

“…How insulin abnormalities may contribute to the symptoms and pathogenesis have been examined in various experimental model systems and role for insulin has been established in molecular and neurophysiological features of memory processing (Zhao and Alkon, 2001). The giving of insulin while maintaining euglycaemia improves memory in both healthy adults and people with AD (Craft et al, 1999;Kern et al, 2001). Insulin also exerts neuroprotection via activation of Akt in neuronal cells (Kim and Han, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Insulin on Hydrogen Peroxide-Induced Oxidative Stress in C6 Glial Cells

Mahesh¹,

Kim²

2009

Biomolecules and Therapeutics

View full text Add to dashboard Cite

-Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. The objective of the present study was to investigate the protective effects of insulin under conditions of oxidative stress induced by hydrogen peroxide (H2O2) in C6 glial cells. Insulin at concentration of 10 −7 M could prevent 12 h H2O2-induced cell death. The formation of reactive oxygen species (ROS), nitric oxide (NO) and 2-thiobarbituric acid-reactive substances (TBARS) were significantly scavenged by insulin pre-treatment in C6 glial cells after H 2 O 2 -induced oxidative stress. Insulin significantly stimulated the phosphorylation of Akt in the cells and the activation of Akt was maintained in response to insulin under H2O2 incubation for 12 h. In conclusion, these results provide evidence that insulin acts as a free radical scavenger and stimulating Akt activity. These data suggest that insulin may be effective in degenerative diseases with oxidative stress.

show abstract

Enhancement of Memory in Alzheimer Disease With Insulin and Somatostatin, but Not Glucose

Abstract: These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD.

Cited by 286 publications

References 50 publications

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

The Protective Effects of Insulin on Hydrogen Peroxide-Induced Oxidative Stress in C6 Glial Cells

Contact Info

Product

Resources

About