PDF(Pubmed)
Abstract：
Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer\'s disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults.
Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ42, Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed.
All autonomic networks were positively associated with Aβ42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected.
The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.
Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ42, Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed.
All autonomic networks were positively associated with Aβ42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected.
The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.
摘要：
背景：自主神经功能的高阶调节是通过特定皮质和皮质下脑区域的协调活动来维持的，统称为中央自主网络(CAN)。在阿尔茨海默病（AD）和痴呆中经常观察到自主神经变化，但迄今为止,尚无研究调查血浆AD生物标志物是否与高危老年人的CAN功能连接变化相关.
方法：从社区招募独立生活的老年人（N=122），没有严重的神经或精神疾病。参与者接受了静息态脑功能磁共振成像，并应用了基于体素的荟萃分析得出的CAN网络，同情,和副交感神经CAN连接使用CONN功能工具箱。将感觉运动网络连接性作为阴性对照进行研究。淀粉样蛋白（Aβ42，Aβ40）的血浆水平，神经丝轻链（NfL），采用数字免疫分析法对胶质纤维酸性蛋白(GFAP)进行检测。使用针对人口统计学协变量和载脂蛋白E（APOE）基因型调整的多元线性回归研究了血浆AD生物标志物与网络内功能连通性之间的关系。还评估了与APOE4载体状态的相互作用效应。
结果：所有自主神经网络均与Aβ42/40比值呈正相关，并且在调整年龄后仍然如此。性别,和APOE4运营商状态。总体和副交感神经网络与GFAP呈负相关。副交感神经CAN和GFAP之间的关系受APOE4载体状态的调节，其中具有低副交感神经CAN连通性的APOE4携带者显示最高的血浆GFAP浓度(B=910.00,P=.004)。感觉运动连接与任何血浆AD生物标志物无关，如预期。
结论：本研究结果表明，CAN功能与血浆AD生物标志物水平相关。具体来说,较低的CAN功能连接与血浆Aβ42/40降低相关，提示脑淀粉样变性，在有AD风险的APOE4携带者中血浆GFAP增加。这些发现可能表明在非常早期的AD中更高阶的自主神经和副交感神经功能障碍,这可能有临床意义。
方法：从社区招募独立生活的老年人（N=122），没有严重的神经或精神疾病。参与者接受了静息态脑功能磁共振成像，并应用了基于体素的荟萃分析得出的CAN网络，同情,和副交感神经CAN连接使用CONN功能工具箱。将感觉运动网络连接性作为阴性对照进行研究。淀粉样蛋白（Aβ42，Aβ40）的血浆水平，神经丝轻链（NfL），采用数字免疫分析法对胶质纤维酸性蛋白(GFAP)进行检测。使用针对人口统计学协变量和载脂蛋白E（APOE）基因型调整的多元线性回归研究了血浆AD生物标志物与网络内功能连通性之间的关系。还评估了与APOE4载体状态的相互作用效应。
结果：所有自主神经网络均与Aβ42/40比值呈正相关，并且在调整年龄后仍然如此。性别,和APOE4运营商状态。总体和副交感神经网络与GFAP呈负相关。副交感神经CAN和GFAP之间的关系受APOE4载体状态的调节，其中具有低副交感神经CAN连通性的APOE4携带者显示最高的血浆GFAP浓度(B=910.00,P=.004)。感觉运动连接与任何血浆AD生物标志物无关，如预期。
结论：本研究结果表明，CAN功能与血浆AD生物标志物水平相关。具体来说,较低的CAN功能连接与血浆Aβ42/40降低相关，提示脑淀粉样变性，在有AD风险的APOE4携带者中血浆GFAP增加。这些发现可能表明在非常早期的AD中更高阶的自主神经和副交感神经功能障碍,这可能有临床意义。
