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Investigating the relationship between IGF-I, IGF-II, and IGFBP-3 concentrations and later-life cognition and brain volume

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posted on 2023-06-10, 03:44 authored by Antoine Salzmann, Sarah-Naomi James, Dylan M Williams, Marcus Richards, Dorina CadarDorina Cadar, Jonathan M Schott, William Coath, Carole H Sudre, Nishi Chaturvedi, Victoria Garfield
Background The insulin/insulin-like signaling (IIS) pathways, including insulin-like growth factors (IGFs), vary with age. However, their association with late-life cognition and neuroimaging parameters is not well characterized. Methods Using data from the British 1946 birth cohort, we investigated associations of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3; measured at 53 and 60-64 years of age) with cognitive performance [word-learning test (WLT) and visual letter search (VLS) at 60-64 years and 69 years of age] and cognitive state [Addenbrooke’s Cognitive Exam III (ACE-III) at 69-71 years of age], and in a proportion, quantified neuroimaging measures [whole brain volume (WBV), white matter hyperintensity volume (WMHV), hippocampal volume (HV)]. Regression models included adjustments for demographic, lifestyle, and health factors. Results Higher IGF-I and IGF-II at 53 years of age was associated with higher ACE-III scores [ß 0.07 95% confidence interval (CI) (0.02, 0.12); scoreACE-III 89.48 (88.86, 90.1), respectively). IGF-II at 53 years of age was additionally associated with higher WLT scores [scoreWLT 20 (19.35, 20.65)]. IGFBP-3 at 60 to 64 years of age was associated with favorable VLS score at 60 to 64 and 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.02, 0.12), respectively], higher memory and cognitive state at 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.01, 0.13), respectively], and reduced WMHV [ß -0.1 (-0.21, -0.00)]. IGF-I/IGFBP-3 at 60 to 64 years of was associated with lower VLS scores at 69 years of age [ß -0.08 (-0.15, -0.02)]. Conclusions Increased measure in IIS parameters (IGF-I, IGF-II, and IGFBP-3) relate to better cognitive state in later life. There were apparent associations with specific cognitive domains (IGF-II relating to memory; IGFBP-3 relating to memory, processing speed, and WMHV; and IGF-I/IGFBP-3 molar ratio related to slower processing speed). IGFs and IGFBP-3 are associated with favorable cognitive function outcomes.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Clinical Endocrinology and Metabolism

ISSN

0021-972X

Publisher

Oxford University Press

Issue

6

Volume

106

Page range

1617-1629

Event location

United States

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2022-05-30

First Open Access (FOA) Date

2022-05-30

First Compliant Deposit (FCD) Date

2022-05-30