Andrew J Westwood1, Alexa Beiser, Charles Decarli, Tamara B Harris, Tai C Chen, Xue-Mei He, Ronenn Roubenoff, Aleksandra Pikula, Rhoda Au, Lewis E Braverman, Philip A Wolf, Ramachandran S Vasan, Sudha Seshadri. 1. From the Department of Neurology (A.J.W., A.B., A.P., R.A., P.A.W., S.S.) and Sections of Preventative Medicine and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine; Department of Biostatistics (A.B.), Boston University School of Public Health, Boston; Framingham Heart Study (A.B., A.P., R.A., P.A.W., R.S.V., S.S.), Framingham, MA; University of California at Davis (C.D.), Sacramento, CA; National Institute on Aging (T.B.H.), Bethesda, MD; Boston University Medical Center (T.C.C., X.-m.H., L.E.B.), Section of Endocrinology, Diabetes, and Nutrition, Boston; Novartis Institutes for Biomedical Research (R.R.), Cambridge, MA.
Abstract
OBJECTIVE: To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages. METHODS: Dementia-free Framingham participants from generation 1 (n = 789, age 79 ± 4 years, 64% women) and generation 2 (n = 2,793, age 61 ± 9 years, 55% women; total = 3,582, age 65 ± 11 years, 57% women) had serum IGF-1 measured in 1990-1994 and 1998-2001, respectively, and were followed prospectively for incident dementia and AD dementia. Brain MRI was obtained in stroke- and dementia-free survivors of both generations 1 (n = 186) and 2 (n = 1,867) during 1999-2005. Baseline IGF-1 was related to risk of incident dementia using Cox models and to total brain and hippocampal volumes using linear regression in multivariable models adjusted for age, sex, APOE ε4, plasma homocysteine, waist-hip ratio, and physical activity. RESULTS: Mean IGF-1 levels were 144 ± 60 μg/L in generation 1 and 114 ± 37 μg/L in generation 2. We observed 279 cases of incident dementia (230 AD dementia) over a mean follow-up of 7.4 ± 3.1 years. Persons with IGF-1 in the lowest quartile had a 51% greater risk of AD dementia (hazard ratio = 1.51, 95% confidence interval: 1.14-2.00; p = 0.004). Among persons without dementia, higher IGF-1 levels were associated with greater total brain volumes (β/SD increment in IGF-1 was 0.55 ± 0.24, p = 0.025; and 0.26 ± 0.06, p < 0.001, for generations 1 and 2, respectively). CONCLUSION: Lower serum levels of IGF-1 are associated with an increased risk of developing AD dementia and higher levels with greater brain volumes even among middle-aged community-dwelling participants free of stroke and dementia. Higher levels of IGF-1 may protect against subclinical and clinical neurodegeneration.
OBJECTIVE: To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages. METHODS:Dementia-free Framingham participants from generation 1 (n = 789, age 79 ± 4 years, 64% women) and generation 2 (n = 2,793, age 61 ± 9 years, 55% women; total = 3,582, age 65 ± 11 years, 57% women) had serum IGF-1 measured in 1990-1994 and 1998-2001, respectively, and were followed prospectively for incident dementia and AD dementia. Brain MRI was obtained in stroke- and dementia-free survivors of both generations 1 (n = 186) and 2 (n = 1,867) during 1999-2005. Baseline IGF-1 was related to risk of incident dementia using Cox models and to total brain and hippocampal volumes using linear regression in multivariable models adjusted for age, sex, APOE ε4, plasma homocysteine, waist-hip ratio, and physical activity. RESULTS: Mean IGF-1 levels were 144 ± 60 μg/L in generation 1 and 114 ± 37 μg/L in generation 2. We observed 279 cases of incident dementia (230 AD dementia) over a mean follow-up of 7.4 ± 3.1 years. Persons with IGF-1 in the lowest quartile had a 51% greater risk of AD dementia (hazard ratio = 1.51, 95% confidence interval: 1.14-2.00; p = 0.004). Among persons without dementia, higher IGF-1 levels were associated with greater total brain volumes (β/SD increment in IGF-1 was 0.55 ± 0.24, p = 0.025; and 0.26 ± 0.06, p < 0.001, for generations 1 and 2, respectively). CONCLUSION: Lower serum levels of IGF-1 are associated with an increased risk of developing AD dementia and higher levels with greater brain volumes even among middle-aged community-dwelling participants free of stroke and dementia. Higher levels of IGF-1 may protect against subclinical and clinical neurodegeneration.
Authors: E R Denton; M Holden; E Christ; J M Jarosz; D Russell-Jones; J Goodey; T C Cox; D L Hill Journal: J Comput Assist Tomogr Date: 2000 Jan-Feb Impact factor: 1.826
Authors: Miranda G Dik; Saskia M F Pluijm; Cees Jonker; Dorly J H Deeg; Marie Z Lomecky; Paul Lips Journal: Neurobiol Aging Date: 2003 Jul-Aug Impact factor: 4.673
Authors: Markus Schubert; Derek P Brazil; Deborah J Burks; Jake A Kushner; Jing Ye; Carrie L Flint; Janet Farhang-Fallah; Pieter Dikkes; Xavier M Warot; Carlos Rio; Gabriel Corfas; Morris F White Journal: J Neurosci Date: 2003-08-06 Impact factor: 6.167
Authors: Maria Clara Selles; Juliana T S Fortuna; Maria F Zappa-Villar; Yasmin P R de Faria; Amanda S Souza; Claudia K Suemoto; Renata E P Leite; Roberta D Rodriguez; Lea T Grinberg; Paula C Reggiani; Sergio T Ferreira Journal: Mol Neurobiol Date: 2019-11-23 Impact factor: 5.590
Authors: T Doi; H Makizako; K Tsutsumimoto; R Hotta; S Nakakubo; K Makino; T Suzuki; H Shimada Journal: J Nutr Health Aging Date: 2018 Impact factor: 4.075
Authors: Vincent Chouraki; Sarah R Preis; Qiong Yang; Alexa Beiser; Shuo Li; Martin G Larson; Galit Weinstein; Thomas J Wang; Robert E Gerszten; Ramachandran S Vasan; Sudha Seshadri Journal: Alzheimers Dement Date: 2017-06-08 Impact factor: 21.566
Authors: Kendra L Puig; Joshua A Kulas; Whitney Franklin; Sharlene G Rakoczy; Giulio Taglialatela; Holly M Brown-Borg; Colin K Combs Journal: Neurobiol Aging Date: 2016-01-06 Impact factor: 4.673