Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Alzheimers Dement. 2018 Aug;14(8):998-1004. doi: 10.1016/j.jalz.2018.03.007. Epub 2018 Apr 19.
We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using a direct magnetic resonance imaging marker of myelin.
Brains of young and old controls, and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed.
MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects.
We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging-based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, and relationship of functional status to myelination status. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials.
我们使用一种直接的磁共振成像髓鞘标志物研究了衰老、轻度认知障碍（MCI）和痴呆症中的脑脱髓鞘。
使用我们最近开发的髓鞘水分分数（MWF）图谱技术对年轻和老年对照组以及患有 MCI、阿尔茨海默病或血管性痴呆的老年患者的大脑进行扫描，该技术提供了比以前可比方法更高的准确性。构建了 MWF、直接且特异性的髓鞘测量、弛豫时间和磁化转移比、间接且非特异性测量的图谱。
与老年对照组相比，MCI 患者的 MWF 降低。阿尔茨海默病或血管性痴呆患者的脱髓鞘更为严重。如预期的那样，MWF 降低伴随着磁化转移比降低和弛豫时间增加。年轻受试者的髓鞘含量大于老年受试者。
我们相信这是使用提供基于磁共振成像的髓鞘定量测量的方法首次在 MCI、阿尔茨海默病和血管性痴呆中证明髓鞘丢失。我们的发现增加了髓鞘化可能代表 MCI 和痴呆症病理学的重要生物标志物的新证据。这项研究支持通过使用这种定量磁共振成像方法在疾病进展的临床研究中以及与髓鞘状态的功能状态关系中研究髓鞘化在 MCI 和痴呆症中的作用。此外，MWF 图谱可能允许髓鞘作为临床试验中的治疗靶点。
