成纤维细胞生长因子 23 与认知障碍：健康、衰老和人体成分研究。
Fibroblast growth factor 23 and cognitive impairment: The health, aging, and body composition study.
机构信息
Tufts Medical Center, Boston, MA, United States of America.
University of Washington, Seattle, WA, United States of America.
出版信息
PLoS One. 2020 Dec 11;15(12):e0243872. doi: 10.1371/journal.pone.0243872. eCollection 2020.
BACKGROUND
Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue.
METHODS
In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho.
RESULTS
The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2.
CONCLUSION
Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.
背景
成纤维细胞生长因子 23（FGF-23）是一种调节磷和维生素 D 代谢的激素，其浓度随着肾功能的下降而增加。过量的成纤维细胞生长因子 23 可能通过促进血管疾病或通过对神经元组织的直接作用来影响大脑功能。
方法
在功能良好的老年人的健康衰老和身体成分研究中，对 2738 个人的完整血清 FGF-23 进行了检测。通过使用改良的迷你精神状态检查（3MSE）和数字符号替代测试（DSST）评估认知功能，3MSE 是一项全面认知功能测试，DSST 主要是一项执行功能测试。使用逻辑回归和泊松回归分别评估 FGF-23 与基线认知功能和认知障碍发生率之间的关系，并根据人口统计学、基线估计肾小球滤过率（eGFR）、尿白蛋白/肌酐比、合并症和其他矿物质代谢指标（包括可溶性 klotho）进行调整。
结果
平均（标准差）年龄为 74（3）岁，女性占 51%，黑人占 39%。中位数（25%，75%）FGF-23 浓度为 47pg/ml（37，60）。392 人通过 3MSE 有明显的认知障碍，461 人通过 DSST 有明显的认知障碍。在这两个认知测试中，FGF-23 与基线认知功能之间没有观察到关联。通过 3MSE 有 277 人出现认知障碍，通过 DSST 有 333 人出现认知障碍。在完全调整的模型中，基线 FGF-23 浓度每增加两倍，与 3MSE 发生认知障碍的风险无关（IRR=1.02[0.88，1.19]完全调整模型）或与 DSST 无关（IRR=0.98[0.84，1.15]）。当按 eGFR 大于或小于 60ml/min/1.73m2 进行分层分析时，我们没有发现差异。
结论
在这项功能良好的老年人群体中，完整的 FGF-23 与基线认知功能或认知障碍发生率无关。
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