Magnetic Resonance Physics of Aging and Dementia Unit, Laboratory of Clinical Investigations, National Institute on Aging, National Institutes of Health, NIA, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA.
Magnetic Resonance Physics of Aging and Dementia Unit, Laboratory of Clinical Investigations, National Institute on Aging, National Institutes of Health, NIA, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA.
Neuroimage. 2020 Dec;223:117369. doi: 10.1016/j.neuroimage.2020.117369. Epub 2020 Sep 12.
Most magnetic resonance imaging (MRI) studies investigating the relationship between regional brain myelination or axonal density and aging have relied upon nonspecific methods to probe myelin and axonal content, including diffusion tensor imaging and relaxation time mapping. While these studies have provided pivotal insights into changes in cerebral architecture with aging and pathology, details of the underlying microstructural alterations have not been fully elucidated. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific multicomponent relaxometry method for imaging of myelin water fraction (MWF), a marker of myelin content, and NODDI, an emerging multicomponent diffusion technique, for neurite density index (NDI) imaging, a proxy of axonal density. We investigated age-related differences in MWF and NDI in several white matter brain regions in a cohort of cognitively unimpaired participants over a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by a decrease at older ages, in agreement with previous work. We found a similarly complex regional association between NDI and age, with several cerebral structures also exhibiting a quadratic, inverted U-shape, relationship. This novel observation suggests an increase in axonal density until the fourth decade of age followed by a rapid loss at older ages. We also observed that these age-related differences in MWF and NDI vary across different brain regions, as expected. Finally, our study indicates no significant association between MWF and NDI in most cerebral structures investigated, although this association approached significance in a limited number of brain regions, indicating the complementary nature of their information and encouraging further investigation. Overall, we find evidence of nonlinear associations between age and myelin or axonal density in a sample of well-characterized adults, using direct myelin and axonal content imaging methods.
大多数研究大脑区域髓鞘形成或轴突密度与衰老之间关系的磁共振成像 (MRI) 研究依赖于弥散张量成像和弛豫时间映射等非特异性方法来探测髓鞘和轴突含量。虽然这些研究为了解衰老和病理学过程中大脑结构的变化提供了重要的见解，但潜在的微观结构变化的细节尚未完全阐明。在本研究中，我们使用 BMC-mcDESPOT 分析，这是一种直接且特异性的多分量弛豫测量法，用于成像髓鞘水分数 (MWF)，这是髓鞘含量的标志物，以及 NODDI，这是一种新兴的多分量扩散技术，用于成像神经丝密度指数 (NDI)，这是轴突密度的替代物。我们在认知未受损参与者的队列中，在广泛的年龄范围内，研究了几个大脑白质区域的 MWF 和 NDI 与年龄相关的差异。我们的结果表明，在所有研究的大脑区域中，MWF 与年龄之间存在二次、倒 U 型关系，表明髓鞘形成一直持续到中年，然后在老年时减少，与先前的研究结果一致。我们发现 NDI 与年龄之间也存在类似的复杂区域关联，一些大脑结构也表现出二次、倒 U 型关系。这一新颖的观察结果表明，轴突密度在 40 岁之前增加，然后在老年时迅速丧失。我们还观察到，MWF 和 NDI 的这些与年龄相关的差异在不同的大脑区域中有所不同，这是意料之中的。最后，我们的研究表明，在大多数研究的大脑结构中，MWF 和 NDI 之间没有显著的相关性，尽管在少数大脑区域中这种相关性接近显著，这表明它们的信息具有互补性，并鼓励进一步研究。总体而言，我们在一组特征明确的成年人样本中使用直接的髓鞘和轴突含量成像方法，发现了年龄与髓鞘或轴突密度之间存在非线性关联的证据。
