Institute for Regenerative Medicine, University of Zurich, Schlieren, Switzerland; Hospital for Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
Neurobiol Aging. 2018 Mar;63:152-161. doi: 10.1016/j.neurobiolaging.2017.12.004. Epub 2017 Dec 12.
Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Aβ) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown. Thirty cognitively normal older adults (age = 70 ± 5.6 years, Mini-Mental State Examination = 29.2 ± 1) received 11-C-Pittsburgh Compound B positron emission tomography for estimating Aβ-plaque density, 7 Tesla fluid-attenuated inversion recovery magnetic resonance imaging for quantifying white matter hyperintensity volume as a marker of small vessel cerebrovascular disease and high-resolution magnetic resonance spectroscopic imaging at 7 Tesla, based on free induction decay acquisition localized by outer volume suppression to investigate tissue-specific neurometabolism in the posterior cingulate and precuneus. Aβ (β = 0.45, p = 0.018) and white matter hyperintensities (β = 0.40, p = 0.046) were independently and interactively (β = -0.49, p = 0.026) associated with a higher ratio of mI over NAA (mI/NAA) in the posterior cingulate and precuneus gray matter but not in the white matter. Our data suggest that cerebrovascular disease and Aβ burden are synergistically associated with AD-related gray matter neurometabolism in older adults.
阿尔茨海默病（AD）是导致老年人认知功能障碍的最常见原因。AD 的病理标志物，如β淀粉样蛋白（Aβ）聚集和神经代谢变化，表现为肌醇（mI）和 N-乙酰天门冬氨酸（NAA）水平改变，通常在认知功能障碍出现前数年就已发生。此外，脑血管疾病在 AD 中很早就发生，但血管和神经代谢脑改变之间的相互作用在很大程度上尚不清楚。30 名认知正常的老年人（年龄=70±5.6 岁，简易精神状态检查=29.2±1）接受了 11-C-Pittsburgh 化合物 B 正电子发射断层扫描，以估计 Aβ 斑块密度，接受 7T 液体衰减反转恢复磁共振成像，以量化白质高信号体积作为小血管脑血管疾病的标志物，以及在 7T 下进行基于自由感应衰减采集的高分辨率磁共振波谱成像，通过外部体积抑制进行局部定位，以研究后扣带回和楔前叶的组织特异性神经代谢。Aβ（β=0.45，p=0.018）和白质高信号（β=0.40，p=0.046）与后扣带回和楔前叶灰质中 mI/NAA 比值升高独立相关（β=0.49，p=0.026），并与灰质中 mI/NAA 比值升高相互作用（β=-0.49，p=0.026），但与白质中 mI/NAA 比值升高无关。我们的数据表明，脑血管疾病和 Aβ 负担与老年人 AD 相关的灰质神经代谢呈协同相关。
