The cause-effect relationship between bone loss and Alzheimer's disease using statistical modeling
The cause-effect relationship between bone loss and Alzheimer's disease using statistical modeling
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DOI：
10.1016/j.mehy.2018.10.024
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发表时间：
2019-01-01
影响因子：
4.7
通讯作者：
Burns, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Loskutova, Natalia;Watts, Amber S.;Burns, Jeffrey M.
背景：动物研究提供了强有力的证据，表明中枢神经系统通过下丘脑的作用通过两个不同的途径直接调节骨重塑，即神经（由瘦素介导）臂和神经体液（由神经激素和生长因子介导）臂。 AD 对骨量中枢调节机制的影响尚不清楚。目的：测试评估阿尔茨海默病 (AD) 下丘脑萎缩和骨质流失之间关系的模型，以及通过神经（瘦素）和神经体液（胰岛素样生长因子 -1、IGF-1）机制的潜在调节。假设：AD 相关的下丘脑结构变化改变骨重塑的神经和神经体液调节系统，并导致早期骨质流失AD.设计：通过路径分析和纵向中介模型对为期两年的纵向研究中获得的数据进行二次数据分析。参与者：作为堪萨斯大学大脑老化项目的一部分收集数据，该项目是一项为期两年的观察性研究，对象为 71 名早期 AD 老年人和 69 名非痴呆对照者。测量：人口统计学特征和骨密度、身体成分和下丘脑体积、瘦素、生长激素和 IGF-1 血清水平的测量结果：AD组下丘脑萎缩和骨质流失呈相关性。数据模型表明，骨质流失可能先于大脑发生可测量的变化。 AD 患者的瘦素在两年内增加，并且瘦素的增加与下丘脑萎缩有关。然而，瘦素或 IGF-1 水平的变化并不介导下丘脑萎缩和骨质流失之间的关系。结论：这项研究扩展了之前的发现，表明 AD 中的骨质流失可能与下丘脑的神经退行性变化（萎缩）有关。需要进一步的研究来探索脑萎缩的作用和骨质流失的介导机制。进一步探索骨质流失与AD之间的时间关系可能具有重要的诊断价值。
Background: Animal studies provide strong evidence that the CNS directly regulates bone remodeling through the actions of the hypothalamus via two distinct pathways, the neural (mediated by leptin) arm and neurohumoral (mediated by neurohormones and growth factors) arm. The impact of AD on central regulatory mechanisms of bone mass is not known.Objectives: To test a model that assesses the relationship between hypothalamic atrophy and bone loss in Alzheimer's disease (AD) and potential mediation through neural (leptin) and neurohumoral (insulin-like growth factor -1, IGF-1) mechanisms.Hypotheses: AD-related hypothalamic structural change alters neural and neurohumoral regulatory systems of bone remodeling and contributes to bone loss in early AD.Design: A secondary data analysis of data obtained in a two-year longitudinal study with path analysis and longitudinal mediation modeling.Participants: The data were collected as a part of the University of Kansas Brain Aging Project, a two-year observational study of 71 older adults with early stage AD and 69 non-demented controls.Measurements: Demographic characteristics and measures of bone density, body composition, and hypothalamic volume, serum levels of leptin, growth hormone, and IGF-1 were collected.Results: Hypothalamic atrophy and bone loss were observed in AD group and were associated. Data modeling suggests that bone loss may precede measurable changes in the brain. Leptin increased over two years in AD and the increase in leptin was associated with hypothalamic atrophy. However, changes in leptin or IGF-1 levels did not mediate the relationship between hypothalamic atrophy and bone loss.Conclusions: This study extends previous findings by suggesting that bone loss in AD may be related to neuro-degenerative changes (atrophy) in the hypothalamus. Further studies are needed to explore the role of brain atrophy and mediating mechanisms in bone loss. Further exploring temporal relationship between bone loss and AD may have an important diagnostic value.