Zhang Xuan, Meirelles Osorio D, Li Zhiguang, Yaffe Kristine, Bryan R Nick, Qiu Chengxuan, Launer Lenore J
Laboratory of Epidemiology and Population Sciences Intramural Research Program, National Institute on Aging, Baltimore, MD, United States.
Departments of Psychiatry and Behavioral Sciences, Neurology, and Epidemiology, University of California, San Francisco, San Francisco, CA, United States.
Front Dement. 2023 Mar 13;2:1110553. doi: 10.3389/frdem.2023.1110553. eCollection 2023.
Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife.
Baseline ( = 612) and five-year follow-up ( = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors.
Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes.
Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.
脑源性神经营养因子水平在身体活跃的人群中较高，而在认知功能障碍人群中较低。本研究调查了脑源性神经营养因子是否介导或改变了中年时期久坐时间与磁共振成像估计的脑容量之间的关联。
基线（n = 612）和五年随访（n = 418）数据来自多中心青年成人冠状动脉风险发展研究的脑磁共振成像子研究，包括黑人和白人参与者（年龄50.3岁，51.6%为女性，38.6%为黑人）。久坐时间（每天小时数）被分为四分位数，低四分位数≤4.3（参照），高四分位数>8.4。研究结果为基线时的全脑、白质、灰质、海马体积以及白质各向异性分数，以及从基线开始的5年变化百分比。该研究使用一般线性回归模型来检验脑源性神经营养因子（自然对数转换）对久坐时间与脑结果之间关联的中介和调节作用。作者对回归模型进行了年龄、性别、种族、颅内体积、教育程度和血管因素的调整。
横断面分析显示，久坐时间最长的基线参与者与久坐时间最短的人群相比，全脑体积较小（-12.2立方厘米；95%置信区间：-20.7，-3.7）、灰质体积较小（-7.8立方厘米；95%置信区间：-14.3，-1.3）以及海马体积较小（-0.2立方厘米；95%置信区间：-0.3，0.0）。脑源性神经营养因子水平并未介导脑测量指标与久坐时间之间的关联。研究发现脑源性神经营养因子可调节久坐时间与全脑和白质体积之间的关联，使得久坐时间高和低的人群之间的脑容量差异随着脑源性神经营养因子水平的升高而减小。纵向分析显示，较高的基线脑源性神经营养因子水平与较少的脑容量下降相关。纵向关联在久坐时间方面没有差异，并且脑源性神经营养因子并未介导或调节久坐时间与脑测量指标变化之间的关联。
较高的脑源性神经营养因子水平可能缓冲久坐时间对大脑的负面影响。
