Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27705, USA.
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27705, USA.
Mech Ageing Dev. 2023 Apr;211:111791. doi: 10.1016/j.mad.2023.111791. Epub 2023 Feb 14.
There is growing literature on applications of biodemographic models, including stochastic process models (SPM), to studying regularities of age dynamics of biological variables in relation to aging and disease development. Alzheimer's disease (AD) is especially good candidate for SPM applications because age is a major risk factor for this heterogeneous complex trait. However, such applications are largely lacking. This paper starts filling this gap and applies SPM to data on onset of AD and longitudinal trajectories of body mass index (BMI) constructed from the Health and Retirement Study surveys and Medicare-linked data. We found that APOE e4 carriers are less robust to deviations of trajectories of BMI from the optimal levels compared to non-carriers. We also observed age-related decline in adaptive response (resilience) related to deviations of BMI from optimal levels as well as APOE- and age-dependence in other components related to variability of BMI around the mean allostatic values and accumulation of allostatic load. SPM applications thus allow revealing novel connections between age, genetic factors and longitudinal trajectories of risk factors in the context of AD and aging creating new opportunities for understanding AD development, forecasting trends in AD incidence and prevalence in populations, and studying disparities in those.
越来越多的文献应用生物人口学模型,包括随机过程模型(SPM),来研究与衰老和疾病发展有关的生物变量的年龄动态规律。阿尔茨海默病(AD)是 SPM 应用的绝佳候选,因为年龄是这种异质复杂特征的主要风险因素。然而,这种应用在很大程度上是缺乏的。本文开始填补这一空白,并将 SPM 应用于来自健康与退休研究调查和与医疗保险相关数据的 AD 发病和体重指数(BMI)纵向轨迹的数据。我们发现,与非携带者相比,APOE e4 携带者对 BMI 轨迹偏离最佳水平的变化更不稳健。我们还观察到与 BMI 偏离最佳水平相关的适应性反应(弹性)的年龄相关性下降,以及与 BMI 围绕均值的变异性以及累积的全身适应负荷相关的其他成分的 APOE 和年龄依赖性。因此,SPM 应用允许在 AD 和衰老的背景下揭示年龄、遗传因素和风险因素的纵向轨迹之间的新联系,为理解 AD 发展、预测人群中 AD 发病率和患病率的趋势以及研究这些差异创造了新的机会。