1 Department of Veterans Affairs Medical Centre, Centre for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
Brain. 2014 May;137(Pt 5):1550-61. doi: 10.1093/brain/awu043. Epub 2014 Mar 12.
Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.
阿尔茨海默病患者的脑血流通过动脉自旋标记磁共振成像测量减少，但尚不清楚这与淀粉样蛋白-β病理学有何关系。我们使用来自阿尔茨海默病神经影像学倡议的 182 名受试者，测试了健康对照者（n=51）、早期（n=66）和晚期（n=41）轻度认知障碍以及有痴呆的阿尔茨海默病患者中，淀粉样蛋白-β与局部脑血流的相关性。基于阿尔茨海默病从淀粉样蛋白-β积累开始，然后以不同轨迹的症状和继发性病理学进展的理论，我们测试了在不同诊断组中，脑血流是否在淀粉样蛋白-β阴性对照者和阳性者之间存在差异，以及淀粉样蛋白-β与脑血流和灰质体积的相关性是否不同。全局淀粉样蛋白-β负荷通过 florbetapir 正电子发射断层扫描测量，8 个预先定义的感兴趣区域的局部血流和体积测量。在大多数脑区，痴呆患者的脑血流减少。在多个区域，淀粉样蛋白-β负荷越高，脑血流越低，与诊断组无关。当比较淀粉样蛋白-β阳性者与阴性对照者时，我们发现几个诊断组的脑血流减少，包括楔前叶、内嗅皮质和海马（痴呆）、下顶叶皮质（晚期轻度认知障碍和痴呆）和下颞叶皮质（早期和晚期轻度认知障碍和痴呆）。淀粉样蛋白-β与脑血流和体积的相关性在疾病谱中不同，高淀粉样蛋白-β与对照组脑血流减少程度更大，以及晚期轻度认知障碍和痴呆时体积减少程度更大相关。除了疾病阶段外，淀粉样蛋白-β病理学还影响从对照组到痴呆患者的脑血流。淀粉样蛋白-β病理学与脑血流和体积的相关性不同，可能在早期阶段导致更多的血流损失，而在晚期疾病阶段则以体积损失为主。
