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.
Neurology. 2014 May 6;82(18):1613-9. doi: 10.1212/WNL.0000000000000382. Epub 2014 Apr 4.
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.
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.
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).
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.
将血清胰岛素样生长因子-1（IGF-1）与无痴呆社区样本中阿尔茨海默病（AD）痴呆的发病风险和脑容量联系起来，该样本跨越中年和老年。
第一代（n=789，年龄 79±4 岁，64%为女性）和第二代（n=2793，年龄 61±9 岁，55%为女性；总计 3582 人，年龄 65±11 岁，57%为女性）的无痴呆Framingham 参与者分别于 1990-1994 年和 1998-2001 年检测血清 IGF-1，并前瞻性随访以确定发生痴呆和 AD 痴呆的风险。在 1999-2005 年期间，从第一代（n=186）和第二代（n=1867）的中风和痴呆幸存者中获得了脑 MRI。使用 Cox 模型将基线 IGF-1 与发病风险相关联，并使用多元回归模型将总脑和海马体积与 IGF-1 相关联，这些模型经过了年龄、性别、APOE ε4、血浆同型半胱氨酸、腰围-臀围比和体力活动的调整。
第一代 IGF-1 水平的平均值为 144±60μg/L，第二代 IGF-1 水平的平均值为 114±37μg/L。在平均 7.4±3.1 年的随访期间，我们观察到 279 例发生痴呆（230 例 AD 痴呆）。IGF-1 处于最低四分位数的人发生 AD 痴呆的风险增加 51%（危险比=1.51，95%置信区间：1.14-2.00；p=0.004）。在没有痴呆的人群中，较高的 IGF-1 水平与总脑容量增加有关（IGF-1 的每标准差增量分别为 0.55±0.24，p=0.025 和 0.26±0.06，p<0.001，分别为第一代和第二代）。
血清 IGF-1 水平较低与 AD 痴呆的发病风险增加有关，而水平较高与脑容量增加有关，即使在无中风和痴呆的中年社区居民中也是如此。较高水平的 IGF-1 可能有助于预防亚临床和临床神经退行性变。
