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Showing content from https://pubmed.ncbi.nlm.nih.gov/35599493/ below:

Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults

Meta-Analysis

Affiliations

• ¹ German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
• ² Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
• ³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
• ⁴ Framingham Heart Study, Framingham, MA, USA.
• ⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
• ⁶ Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.
• ⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
• ⁸ DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
• ⁹ Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
• ¹⁰ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
• ¹¹ Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
• ¹² Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
• ¹³ Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁴ Department of Neurology, Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁵ Department of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA.
• ¹⁶ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
• ¹⁷ Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.

• PMID: 35599493
• PMCID: PMC9472289
• DOI: 10.3233/JAD-220356

Item in Clipboard

Meta-Analysis

Katharina Wittfeld et al. J Alzheimers Dis. 2022.

• ¹ German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
• ² Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
• ³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
• ⁴ Framingham Heart Study, Framingham, MA, USA.
• ⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
• ⁶ Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.
• ⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
• ⁸ DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
• ⁹ Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
• ¹⁰ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
• ¹¹ Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
• ¹² Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
• ¹³ Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁴ Department of Neurology, Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA.
• ¹⁵ Department of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA.
• ¹⁶ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
• ¹⁷ Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.

• PMID: 35599493
• PMCID: PMC9472289
• DOI: 10.3233/JAD-220356

Item in Clipboard

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 [β] [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.

Keywords: Alzheimer’s disease endophenotype; C-reactive protein; cohort study; epidemiology; hippocampus; insulin-like growth factor; neuroimaging; white matter hyperintensity.

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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

Forest plots of cohort-specific and…

Forest plots of cohort-specific and meta-analysis results for the associations between (A) IGF-1 and MRI measures, and (B) IGFBP-3 and MRI measures. Beta estimates and 95% confidence intervals (CI) are presented graphically in the center, where the square represents beta coefficients and the error bars the 95% confidence intervals per cohort according to the text on the right column. Meta-analysis results derived from random-effects (RE) models are presented with diamonds and italicized text. Models are adjusted for age, age-squared, sex, time between blood draw and MRI, waist-to-hip ratio, systolic blood pressure, hypertension treatment, diabetes mellitus, current smoking, and prevalent cardiovascular disease. *p<0.05 after FDR correction. Abbreviations: FHS: Framingham Heart Study Generation 3, SHIP: Study of Health in Pomerania Trend, RE Meta-Analysis: random effects meta-analysis, IGF-1: insulin-like growth factor 1, IGFBP-3: insulin-like growth factor binding protein-3, GM: gray matter, WM: white matter, WMH: white matter hyperintensity.

Forest plots…

Forest plots of cohort-specific and meta-analysis results for the associations between (A) IGF-1 and MRI measures in participants with CRP concentrations <75

percentile, (B) IGF-1 and MRI measures in participants with CRP concentrations ≥75

percentile, (C) IGFBP-3 and MRI measures in participants with CRP concentrations <75

percentile, and (D) IGFBP-3 and MRI measures in participants with CRP concentrations ≥75

percentile. Beta estimates and 95% confidence intervals (CI) are presented graphically in the center, where the square represents beta coefficients and the error bars the 95% confidence intervals per cohort according to the text on the right column. Meta-analysis results derived from random-effects (RE) models are presented with diamonds and italicized text. Models are adjusted for age, age-squared, sex, time between blood draw and MRI, waist-to-hip ratio, systolic blood pressure, hypertension treatment, diabetes mellitus, current smoking, and prevalent cardiovascular disease. *p<0.05 after FDR correction. Meta-analysis results are derived from random-effects models and presented in italic.

Abbreviations: FHS Gen 3: Framingham Heart Study Generation 3, SHIP-TREND: Study of Health in Pomerania TREND, IGF-1: insulin-like growth factor 1, IGFBP-3: insulin-like growth factor binding protein-3, GM: gray matter, WM: white matter, WMH: white matter hyperintensity, CRP: C-reactive protein

Forest plots of…

Forest plots of cohort-specific and meta-analysis results for the interactions of (A) IGF-1 and dichotomized CRP on MRI measures and (B) IGFBP-3 and dichotomized CRP on MRI measures. CRP was dichotomized according to the 75^th percentile (<75^th percentile, ≥75^th percentile). Beta estimates and 95% confidence intervals (CI) are presented graphically in the center, where the square represents beta coefficients and the error bars the 95% confidence intervals per cohort according to the text on the right column. Meta-analysis results derived from random-effects (RE) models are presented with diamonds. Models are adjusted for age, age-squared, sex, time between blood draw and MRI, waist-to-hip ratio, systolic blood pressure, hypertension treatment, diabetes mellitus, current smoking, and prevalent cardiovascular disease. Abbreviations: FHS Gen 3: Framingham Heart Study Generation 3, SHIP-TREND: Study of Health in Pomerania TREND, IGF-1: insulin-like growth factor 1, IGFBP-3: insulin-like growth factor binding protein-3, GM: gray matter, WM: white matter, WMH: white matter hyperintensity, CRP: C-reactive protein

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• Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.

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• The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

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• Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer's Disease Mice via Transcriptomic and Cellular Analysis.

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