Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert
Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert
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DOI：
10.1016/j.neuroimage.2020.116607
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发表时间：
2020-05-01
期刊：
影响因子：
5.7
通讯作者：
Ferreira, Daniel
中科院分区：
文献类型：
--
作者：
Nemy, Milan;Cedres, Nira;Ferreira, Daniel
胆碱能系统的完整性在正常衰老和神经系统疾病（包括阿尔茨海默病和血管性认知障碍）中的认知下降中起着核心作用。以往的神经影像学研究主要集中在基底前脑胆碱能神经元的完整性或其亚区Meynert基底核（NBM）。使用扩散张量成像数据的纤维束成像可以实现NBM白色物质投影的建模。我们调查了262名认知正常个体（39-77岁，53%为女性）的NBM体积、NBM白色物质投射、小血管疾病（SVD）和年龄对注意力和记忆力表现的贡献。我们开发了一个多模态MRI管道，用于NBM分割和NBM白色物质投影的基于扩散的跟踪，并计算了白色物质低密度（WM-hypo）作为SVD的标记。我们成功地跟踪途径，密切类似的空间布局的胆碱能系统，如在以前的尸检和DTI纤维束成像研究。我们发现高WM-低负荷与年龄较大、男性以及注意力和记忆力较低有关。高WM-低负荷也与胆碱能系统的完整性降低有关，超出了年龄的影响。在一个多变量模型中，年龄和完整性的NBM白色物质的预测是更强的贡献者比WM-低负荷和NBM体积的性能在注意力和记忆。我们的结论是NBM白色物质投射的完整性在认知老化中起着重要作用。这和其他现代神经影像学方法提供了新的机会，重新评估认知老化的胆碱能假说。
The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer's disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39-77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.