Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank

Zhi Cao; Jiahao Min; Qilong Tan; Keyi Si; Hongxi Yang; Chenjie Xu

doi:10.1186/s13195-023-01288-5

Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank

Alzheimers Res Ther. 2023 Aug 22;15(1):140. doi: 10.1186/s13195-023-01288-5.

Authors

Zhi Cao^{1

2}, Jiahao Min¹, Qilong Tan^{2

3}, Keyi Si⁴, Hongxi Yang⁵, Chenjie Xu⁶

Affiliations

¹ School of Public Health, Hangzhou Normal University, NO.2318, Yuhangtang Road, Yuhang District, Hangzhou, 311121, China.
² School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
³ School of Public Health, Harbin Medical University, Harbin, China.
⁴ Department of Health Statistics, Naval Medical University, Shanghai, China.
⁵ School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
⁶ School of Public Health, Hangzhou Normal University, NO.2318, Yuhangtang Road, Yuhang District, Hangzhou, 311121, China. xuchenjie@hznu.edu.cn.

Abstract

Background: The effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features.

Methods: This prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest - dementia, stroke, and Parkinson's disease (PD) - at enrollment (2006-2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014.

Results: During a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose-response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (β = 2.98 × 10^-4, P < 0.001) and hippocampus (β = 3.37 × 10^-4, P = 0.002) and smaller white matter hyperintensity (β = -3.12 × 10^-3, P < 0.001).

Conclusions: Apart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.

Keywords: Brain volume; Dementia; IGF-1; Parkinson’s disease; Stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks
Brain / diagnostic imaging
Dementia* / diagnostic imaging
Dementia* / epidemiology
Humans
Insulin-Like Growth Factor I
Prospective Studies
Stroke*
United Kingdom / epidemiology

Substances

Insulin-Like Growth Factor I

Supplementary concepts

Insulin-Like Growth Factor I Deficiency