PMID- 35599493 OWN - NLM STAT- MEDLINE DCOM- 20220707 LR - 20230930 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 88 IP - 1 DP - 2022 TI - Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults. PG - 311-322 LID - 10.3233/JAD-220356 [doi] AB - BACKGROUND: Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. OBJECTIVE: To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation. METHODS: We included participants from the Framingham Heart Study (n = 1,852, mean age 46+/-8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50+/-13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons. RESULTS: Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [beta] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes. CONCLUSION: Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife. FAU - Wittfeld, Katharina AU - Wittfeld K AD - German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany. AD - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. FAU - Raman, Mekala R AU - Raman MR AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Framingham Heart Study, Framingham, MA, USA. FAU - Conner, Sarah C AU - Conner SC AD - Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. FAU - Aslam, Asra AU - Aslam A AD - Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA. FAU - Teumer, Alexander AU - Teumer A AD - Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. AD - Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland. FAU - Nauck, Matthias AU - Nauck M AD - DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. AD - Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Hosten, Norbert AU - Hosten N AD - Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. FAU - Habes, Mohamad AU - Habes M AD - Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA. AD - Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Neurology, Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA. FAU - DeCarli, Charles AU - DeCarli C AD - Department of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA. FAU - Vasan, Ramachandran S AU - Vasan RS AD - Framingham Heart Study, Framingham, MA, USA. AD - Department of Medicine, Boston University School of Medicine, Boston, MA, USA. AD - Department of Epidemiology, Boston University School of Public Health, Boston MA, USA. FAU - Beiser, Alexa S AU - Beiser AS AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Framingham Heart Study, Framingham, MA, USA. AD - Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. FAU - Himali, Jayandra J AU - Himali JJ AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Framingham Heart Study, Framingham, MA, USA. AD - Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. AD - Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA. FAU - Seshadri, Sudha AU - Seshadri S AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Framingham Heart Study, Framingham, MA, USA. AD - Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA. FAU - Grabe, Hans J AU - Grabe HJ AD - German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany. AD - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. FAU - Satizabal, Claudia L AU - Satizabal CL AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Framingham Heart Study, Framingham, MA, USA. AD - Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA. LA - eng GR - UH3 NS100605/NS/NINDS NIH HHS/United States GR - R01 AG054076/AG/NIA NIH HHS/United States GR - HHSN268201500001C/HL/NHLBI NIH HHS/United States GR - T32 GM074905/GM/NIGMS NIH HHS/United States GR - T32 HL125232/HL/NHLBI NIH HHS/United States GR - R01 HL077477/HL/NHLBI NIH HHS/United States GR - R01 AG049607/AG/NIA NIH HHS/United States GR - R01 AG033193/AG/NIA NIH HHS/United States GR - R01 HL127659/HL/NHLBI NIH HHS/United States GR - R01 NS017950/NS/NINDS NIH HHS/United States GR - UF1 NS125513/NS/NINDS NIH HHS/United States GR - HHSN268201500001I/HL/NHLBI NIH HHS/United States GR - RF1 AG054409/AG/NIA NIH HHS/United States GR - P30 AG066546/AG/NIA NIH HHS/United States GR - U01 AG052409/AG/NIA NIH HHS/United States GR - UH2 NS100605/NS/NINDS NIH HHS/United States GR - N01HC25195/HL/NHLBI NIH HHS/United States GR - 75N92019D00031/HL/NHLBI NIH HHS/United States GR - P30 AG010129/AG/NIA NIH HHS/United States GR - R01 AG031287/AG/NIA NIH HHS/United States GR - U01 AG049505/AG/NIA NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Biomarkers) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Adult MH - *Alzheimer Disease/diagnostic imaging MH - Biomarkers MH - C-Reactive Protein/metabolism MH - Female MH - Humans MH - Inflammation/diagnostic imaging MH - *Insulin-Like Growth Factor Binding Protein 3 MH - Insulin-Like Growth Factor I/analysis MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged PMC - PMC9472289 MID - NIHMS1833978 OTO - NOTNLM OT - Alzheimer's disease endophenotype OT - C-reactive protein OT - cohort study OT - epidemiology OT - hippocampus OT - insulin-like growth factor OT - neuroimaging OT - white matter hyperintensity COIS- CONFLICTS OF INTEREST HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care. Dr. Seshadri is a consultant for Biogen Dr. Charles DeCarli is a consultant to Novartis on a safety trial for heart failure Other authors have nothing to report EDAT- 2022/05/24 06:00 MHDA- 2022/07/08 06:00 PMCR- 2022/09/14 CRDT- 2022/05/23 02:53 PHST- 2022/05/24 06:00 [pubmed] PHST- 2022/07/08 06:00 [medline] PHST- 2022/05/23 02:53 [entrez] PHST- 2022/09/14 00:00 [pmc-release] AID - JAD220356 [pii] AID - 10.3233/JAD-220356 [doi] PST - ppublish SO - J Alzheimers Dis. 2022;88(1):311-322. doi: 10.3233/JAD-220356.