Ighodaro Eseosa T, Abner Erin L, Fardo David W, Lin Ai-Ling, Katsumata Yuriko, Schmitt Frederick A, Kryscio Richard J, Jicha Gregory A, Neltner Janna H, Monsell Sarah E, Kukull Walter A, Moser Debra K, Appiah Frank, Bachstetter Adam D, Van Eldik Linda J, Nelson Peter T
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
J Cereb Blood Flow Metab. 2017 Jan;37(1):201-216. doi: 10.1177/0271678X15621574. Epub 2016 Jan 6.
Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor.
脑小动脉硬化病理的危险因素和认知后遗症尚未完全明确。为了解决这一问题，我们使用了来自国家阿尔茨海默病协调中心和阿尔茨海默病神经影像倡议数据集的多模态数据。先前的研究表明，与年轻队列相比，“最年长者”存在不同的神经退行性疾病结局和临床病理相关性证据。因此，我们使用国家阿尔茨海默病协调中心数据集，根据死亡年龄将两组的临床和神经病理学数据进行了分析：<80岁（n = 1008）和≥80岁（n = 1382）。在两个年龄组中，严重脑小动脉硬化均与整体认知测试表现较差相关。高血压（而非糖尿病）是较年轻组的脑小动脉硬化危险因素。在死亡年龄≥80岁的组中，一种先前与衰老相关的海马硬化有关的ABCC9基因变异（rs704180）也与脑小动脉硬化有关。一项事后动脉自旋标记神经成像实验表明，ABCC9基因型与脑血流量受损有关；在来自阿尔茨海默病神经影像倡议的一个便利样本（n = 15，纯合个体）中，非风险基因型携带者与风险基因型携带者相比，表现出更高的全脑血流量。我们得出结论，脑小动脉硬化与认知状态改变和一种新的血管遗传危险因素有关。
