Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 and risk of postoperative cognitive dysfunction.

Jue Jiang,Jia Yan,Zhifeng Chen,Hong Jiang,Bing Liang,Ying Zhang

doi:10.1186/s40064-015-1586-2

Abstract

Insulin-like growth factor (IGF)-1 is implicated in learning and memory. Experimental studies have suggested that the IGF-1 system is beneficial in cognition, especially in Alzheimer’s disease (AD), by opposing Aβ amyloid processing and hyperphosphorylated tau toxicity. Low IGF-I and insulin-like growth factor binding protein (IGFBP)-3 serum levels are significantly associated with AD. To assess the relationship between circulating IGF-I and IGFBP3 levels and change of postoperative cognition. The study was performed in patients scheduled for elective head and neck carcinoma surgery under general anesthesia. On the day before the operation and postoperative days 1, 3 and 7, mini-mental state examination (MMSE) was performed by the same doctor, and blood samples were collected at 08:00 h after overnight fasting. The circulating levels of IGF-1 and IGFBP3 were measured by enzyme-linked immunosorbent assay. One hundred and two patients completed all four MMSE tests and forty-four of them completed all the four blood samples collection. Postoperative circulating IGF-1 level, ratio of IGF-1/IGFBP3 and MMSE score significantly decreased, whereas IGFBP3 level significantly increased compared with preoperative values in total patients. The change trends of circulating IGF-1 level and MMSE score were similar. Preoperative circulating IGF-1 level, ratio and MMSE score were significantly lower in POCD group compared to non-POCD group. There was no significant difference in preoperative level of circulating IGFBP3 between the two groups. Preoperative circulating IGF-1 level was negatively correlated with age and positively with MMSE. Logistic regression analysis revealed that lower preoperative IGF-1 level and elderly patients increased the odds of POCD. Down-regulation of circulating IGF-1 level may be involved in the mechanism of postoperative cognitive dysfunction. Older patients had lower circulating IGF-1 levels and were more susceptible to POCD.

Highlights

Since Savageau first described an association between postoperative cognitive dysfunction (POCD), surgery and anesthesia exposure in 1982 (Hartmann et al 2007), many studies have documented the onset of POCD, which manifests as a decline in brain function, typically resolving within 12 months
Serum insulin-like growth factor (IGF)-I levels positively correlate with cognitive status (Aleman et al 1999), and a similar correlation in mice unveiled a trophic action of circulating IGF-I on glutamate neurotransmission affecting synaptic plasticity and non-POCD groups. **P < 0.01, *P < 0.05
IGF-1 can be produced in the brain (Alvarez et al 2007), but it is mainly produced in the liver, and can enter the brain via the blood–brain barrier (Creyghton et al 2004)

Summary

Introduction

Since Savageau first described an association between postoperative cognitive dysfunction (POCD), surgery and anesthesia exposure in 1982 (Hartmann et al 2007), many studies have documented the onset of POCD, which manifests as a decline in brain function, typically resolving within 12 months. Evidence gathered from human studies shows a positive correlation between insulin-like growth factor (IGF)-I levels and mental ability (Lan et al 2012), while cognitive impairment has been found in human patients affected by growth hormone/IGF-I deficiency (Hanning 2005). Measurement of circulating IGFBP3 levels, in addition to IGF-1 levels, allows the amount of bioavailable IGF-1 to be determined (Alvarez et al 2006). In contrast to IGFBP1 to IGFBP6, which bind to the IGFs (Firth and Baxter 2002), IGFBP7 is a critical regulator of memory consolidation that can attenuate the function of ILPs (Agbemenyah et al 2013) and can directly bind to the IGF-1R and thereby inhibit its activity (Evdokimova et al 2012). The relationship between circulating IGFBP7 level and POCD had been discussed in previous work (Jiang et al 2015)

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Conclusion