Section of Endocrinology, Diabetes, Nutrition, and Weight Management, Boston University Chobanian & Avedisian School of Medicine (BUCASM), Boston, MA, USA.
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.
J Alzheimers Dis. 2023;95(2):561-572. doi: 10.3233/JAD-230289.
Cardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process.
To determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology.
We included dementia and stroke free participants from the Framingham Heart Study Third Generation and Offspring cohorts who had accelerometery and brain MRI data (n = 2,507, 53.9% women, mean age 53.9 years). We examined mediation by the 2017-revised Framingham Stroke Risk Profile (FSRP, using weights for age, cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications, and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of physical inactivity with brain aging, adjusting for age, age-squared, sex, accelerometer wear time, cohort, time from exam-to-MRI, and season. We similarly assessed mediation by an epigenetic age-prediction algorithm, GrimAge, in a smaller sample of participants who had DNA methylation data (n = 1,418).
FSRP and HOMA-IR explained 8.3-20.5% of associations of higher moderate-to-vigorous physical activity (MVPA), higher steps, and lower sedentary time with higher brain volume. Additionally, FSRP and GrimAge explained 10.3-22.0% of associations of physical inactivity with lower white matter diffusivity and FSRP explained 19.7% of the association of MVPA with lower free water accumulation.
Our results suggest that cardiometabolic risk factors and epigenetic patterns partially mediate the associations of physical inactivity with lower brain volume, higher white matter diffusivity, and aggregation of free water in the extracellular compartments of the brain.
身体活动不足的个体中，心血管代谢风险因素和表观遗传模式增加，与大脑衰老过程加速有关。
确定心血管代谢风险因素和表观遗传模式是否介导身体活动不足与不利的大脑形态之间的关联。
我们纳入了弗雷明汉心脏研究第三代和后代队列中无痴呆和中风的参与者，他们有加速度计和脑 MRI 数据（n=2507，53.9%为女性，平均年龄 53.9 岁）。我们使用年龄、心血管疾病、房颤、糖尿病和吸烟状况、降压药物和收缩压的权重，通过 2017 年修订的弗雷明汉中风风险评分（FSRP），以及胰岛素抵抗的稳态模型（HOMA-IR），检验了模型中身体活动不足与大脑老化之间关联的中介作用，调整了年龄、年龄平方、性别、加速度计佩戴时间、队列、从检查到 MRI 的时间和季节。我们还在一个较小的有 DNA 甲基化数据的参与者样本中（n=1418），通过 GrimAge 评估了中介作用。
FSRP 和 HOMA-IR 解释了更高强度的中等到剧烈体力活动（MVPA）、更高的步数和更低的久坐时间与更高的大脑体积之间关联的 8.3-20.5%。此外，FSRP 和 GrimAge 解释了身体活动不足与较低的白质扩散率之间关联的 10.3-22.0%，FSRP 解释了 MVPA 与较低的游离水积聚之间关联的 19.7%。
我们的结果表明，心血管代谢风险因素和表观遗传模式部分介导了身体活动不足与较低的大脑体积、较高的白质扩散率以及脑细胞外间隙游离水的聚集之间的关联。
