Alzheimer’s Research & Therapy (Aug 2023)

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
https://doi.org/10.1186/s13195-023-01288-5
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 10

Abstract

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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.

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