PMID- 33631000 OWN - NLM STAT- MEDLINE DCOM- 20211102 LR - 20240320 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 106 IP - 6 DP - 2021 May 13 TI - Investigating the Relationship Between IGF-I, IGF-II, and IGFBP-3 Concentrations and Later-Life Cognition and Brain Volume. PG - 1617-1629 LID - 10.1210/clinem/dgab121 [doi] AB - 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. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Salzmann, Antoine AU - Salzmann A AUID- ORCID: 0000-0001-7877-9876 AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. FAU - James, Sarah-Naomi AU - James SN AUID- ORCID: 0000-0002-3800-4416 AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. FAU - Williams, Dylan M AU - Williams DM AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Richards, Marcus AU - Richards M AUID- ORCID: 0000-0001-9191-2192 AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. FAU - Cadar, Dorina AU - Cadar D AUID- ORCID: 0000-0003-1398-5841 AD - Department of Behavioural Science and Health, University College London, London, UK. FAU - Schott, Jonathan M AU - Schott JM AUID- ORCID: 0000-0003-2059-024X AD - Department of Neurodegenerative Disease, The Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. FAU - Coath, William AU - Coath W AUID- ORCID: 0000-0002-3976-9461 AD - Department of Neurodegenerative Disease, The Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. FAU - Sudre, Carole H AU - Sudre CH AD - Department of Neurodegenerative Disease, The Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. AD - School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK. FAU - Chaturvedi, Nishi AU - Chaturvedi N AUID- ORCID: 0000-0002-6211-2775 AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. FAU - Garfield, Victoria AU - Garfield V AUID- ORCID: 0000-0002-5127-0890 AD - MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK. LA - eng GR - EP-W-17-011/EPA/EPA/United States GR - MC_UU_0019/2/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00019/1/MRC_/Medical Research Council/United Kingdom GR - MC_UU_0019/3/MRC_/Medical Research Council/United Kingdom GR - R01 AG017644/AG/NIA NIH HHS/United States GR - MC_UU_12019/3/MRC_/Medical Research Council/United Kingdom GR - MC_ST_LHA_2019/MRC_/Medical Research Council/United Kingdom GR - CSUB19166/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00019/3/MRC_/Medical Research Council/United Kingdom GR - 15/0005250/BHF_/British Heart Foundation/United Kingdom PT - Historical Article PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (IGF1 protein, human) RN - 0 (IGF2 protein, human) RN - 0 (IGFBP3 protein, human) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 67763-97-7 (Insulin-Like Growth Factor II) SB - IM MH - Age Factors MH - Aging/physiology MH - Brain/*anatomy & histology/diagnostic imaging MH - Cognition/*physiology MH - Cohort Studies MH - Female MH - History, 20th Century MH - History, 21st Century MH - Humans MH - Insulin-Like Growth Factor Binding Protein 3/analysis/*blood MH - Insulin-Like Growth Factor I/analysis/*metabolism MH - Insulin-Like Growth Factor II/analysis/*metabolism MH - Male MH - Middle Aged MH - Organ Size MH - United Kingdom PMC - PMC8118585 OTO - NOTNLM OT - IGF-I OT - IGF-II OT - aging OT - brain volume OT - cognition OT - epidemiology EDAT- 2021/02/26 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/02/25 CRDT- 2021/02/25 17:17 PHST- 2020/10/14 00:00 [received] PHST- 2021/02/26 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/02/25 17:17 [entrez] PHST- 2021/02/25 00:00 [pmc-release] AID - 6149969 [pii] AID - dgab121 [pii] AID - 10.1210/clinem/dgab121 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2021 May 13;106(6):1617-1629. doi: 10.1210/clinem/dgab121.