Spielberg Jeffrey M, Sadeh Naomi, Leritz Elizabeth C, McGlinchey Regina E, Milberg William P, Hayes Jasmeet P, Salat David H
Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware, 19716.
Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Massachusetts, 02130.
Hum Brain Mapp. 2017 Jun;38(6):3249-3261. doi: 10.1002/hbm.23587. Epub 2017 Mar 31.
Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Mean = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc.
越来越多的证据表明，血清胆固醇和其他心血管疾病风险因素会加剧与年龄相关的认知衰退的正常轨迹。然而，这种情况发生的神经机制在很大程度上仍然未知。为了了解胆固醇对脑网络的影响，我们将图论应用于一大群早中年退伍军人（N = 206，平均年龄 = 32岁）的静息态功能磁共振成像（fMRI）数据。出现了一个以颞上沟岸为中心的网络，该网络显示出与年龄相关的去耦合（即随着年龄增长网络连接性降低），但仅在临床总胆固醇升高（≥180 mg/dL）的参与者中出现。至关重要的是，这个网络中的去耦合与更大的日常功能障碍相对应，并介导了与年龄相关的心理运动速度下降。最后，对网络组织的检查揭示了颞上沟岸存在与年龄相关的去分化模式，同样仅在胆固醇水平较高的情况下出现。更具体地说，年龄与模块内通信减少（以内模块度Z分数为指标）和模块间通信增加（以参与系数为指标）相关，但仅在临床胆固醇升高的参与者中如此。后续分析表明，所有这些发现都是由低密度脂蛋白（LDL）水平驱动的，而不是高密度脂蛋白（HDL）或甘油三酯，这很有意思，因为LDL水平与心血管疾病风险增加有关，而HDL水平似乎与此类疾病呈负相关。这些发现为胆固醇对脑健康的有害影响提供了新的见解，并表明胆固醇通过破坏与整合过程和行为控制相关回路的连接性，加速了年龄对神经轨迹的影响。《人类大脑图谱》38:3249 - 3261，2017年。© 2017威利期刊公司。
