Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic.
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Faculty of Psychology, University of La Laguna, La Laguna, Tenerife, Spain.
Neuroimage. 2020 May 1;211:116607. doi: 10.1016/j.neuroimage.2020.116607. Epub 2020 Feb 6.
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.
胆碱能系统的完整性在正常衰老和包括阿尔茨海默病和血管性认知障碍在内的神经退行性疾病中的认知能力下降中起着核心作用。大多数先前的神经影像学研究都集中在胆碱能基底前脑的完整性上，或者其亚区——梅内尔特基底核（NBM）上。使用弥散张量成像数据的束流追踪可能使 NBM 白质投射的建模成为可能。我们研究了 NBM 体积、NBM 白质投射、小血管疾病（SVD）和年龄对 262 名认知正常个体（39-77 岁，53%为女性）的注意力和记忆力表现的影响。我们开发了一种用于 NBM 分割和基于扩散的 NBM 白质投射追踪的多模态 MRI 管道，并计算了白质低信号（WM-hypo）作为 SVD 的标志物。我们成功地追踪了与先前的尸检和 DTI 束流追踪研究中所见的胆碱能系统的空间布局非常相似的途径。我们发现，WM-hypo 负荷高与年龄较大、男性和注意力及记忆力表现较差有关。WM-hypo 负荷高还与胆碱能系统的完整性降低有关，这种相关性超出了年龄的影响。在多变量模型中，年龄和 NBM 白质投射的完整性比 WM-hypo 负荷和 NBM 体积对注意力和记忆力表现的贡献更大。我们的结论是，NBM 白质投射的完整性在认知衰老中起着基础性的作用。这一发现和其他现代神经影像学方法为重新评估认知衰老的胆碱能假说提供了新的机会。
