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

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The insulin/insulin-like signalling (IIS) pathways, including Insulin-like Growth Factors (IGFs), varies with age. However, their association with late-life cognition and neuroimaging parameters is not well characterised.Using data from the British 1946 birth cohort we investigated associations of IGF-I, -II and IGFBP-3 (measured at 53 and 60-64 years) with cognitive performance (word learning test (WLT) and visual letter search (VLS) – at 60-64y and 69y) and cognitive state (Addenbrooke’s Cognitive Exam-III (ACE-III) – at 69-71y), 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.Higher IGF-I and IGF-II at 53y was associated with higher ACE-III scores (ß 0.07 95%CI [0.02,0.12]; scoreACE-III 89.48 [88.86,90.1], respectively). IGF-II at age 53y was additionally associated with higher WLT scores (scoreWLT 20 [19.35,20.65]). IGFBP-3 at 60-64y was associated with favourable VLS score at 60-64y and 69y (ß 0.07 [0.01,0.12]; ß 0.07 [0.02,0.12], respectively), higher memory and cognitive state at 69y (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 60-64y was associated with lower VLS scores at 69y (ß -0.08, [-0.15,-0.02]).Increased measure in IIS parameters (IGF-I, -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 to memory, processing speed and WMHV; and IGF-I/IGFBP-3 molar ratio with slower processing speed). IGFs and IGFBP-3 are associated with favourable cognitive function outcomes.

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Authors: Antoine Salzmann, Sarah-Naomi James, Dylan M Williams, Marcus Richards, Dorina Cadar, Jonathan M Schott, William Coath, Carole H Sudre, Nishi Chaturvedi, Victoria Garfield