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

Salzmann, Antoine, James, Sarah-Naomi, Williams, Dylan M, Richards, Marcus, Cadar, Dorina, Schott, Jonathan M, Coath, William, Sudre, Carole H, Chaturvedi, Nishi and Garfield, Victoria (2021) Investigating the relationship between IGF-I, IGF-II, and IGFBP-3 concentrations and later-life cognition and brain volume. Journal of Clinical Endocrinology and Metabolism, 106 (6). pp. 1617-1629. ISSN 0021-972X

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Abstract

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.

Item Type: Article
Keywords: IGF-I, IGF-II, aging, brain volume, cognition, epidemiology, Age Factors, Aging, Brain, Cognition, Cohort Studies, Female, History, 20th Century, History, 21st Century, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Male, Middle Aged, Organ Size, United Kingdom
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 30 May 2022 13:07
Last Modified: 30 May 2022 13:15
URI: http://sro.sussex.ac.uk/id/eprint/106189

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