淀粉样蛋白和血管标志物对皮质下血管性痴呆认知功能衰退的影响
Effects of amyloid and vascular markers on cognitive decline in subcortical vascular dementia.
作者信息
Ye Byoung Seok, Seo Sang Won, Kim Jung-Hyun, Kim Geon Ha, Cho Hanna, Noh Young, Kim Hee Jin, Yoon Cindy W, Woo Sook-Young, Kim Sook Hui, Park Hee Kyung, Kim Sung Tae, Choe Yearn Seong, Lee Kyung Han, Kim Jae Seung, Oh Seung Jun, Kim Changsoo, Weiner Michael, Lee Jae-Hong, Na Duk L
机构信息
From the Departments of Neurology (B.S.Y., S.W.S., J.-H.K., H.J.K., D.L.N.), Radiology (S.T.K.), and Nuclear Medicine (Y.S.C., K.H.L.), Samsung Medical Center, Sungkyunkwan University School of Medicine; the Departments of Neurology (B.S.Y.) and Preventive Medicine (C.K.), Yonsei University College of Medicine; the Neuroscience Center (S.W.S., H.J.K., D.L.N.), Samsung Medical Center; the Ewha Womans University School of Medicine (G.H.K.); the Department of Neurology (H.C.), Yonsei University Gangnam Hospital, Seoul; the Department of Neurology (Y.N.), Gachon University Gil Medical Center; the Department of Neurology (C.W.Y.), Inha University School of Medicine, Incheon; the Biostatistics Team (S.-y.W.), Samsung Biomedical Research Institute; Merck, Sharp, and Dohme (MSD) (S.H.K.), Seoul; the Department of Neurology (H.K.P.), Inje University Ilsan Paik Hospital, Goyang; the Departments of Nuclear Medicine (J.S.K., S.J.O.) and Neurology (J.-H.L.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; and Center for Imaging of Neurodegenerative Disease (M.W.), University of California, San Francisco.
出版信息
Neurology. 2015 Nov 10;85(19):1687-93. doi: 10.1212/WNL.0000000000002097. Epub 2015 Oct 14.
OBJECTIVE
To determine the independent and synergistic effects of amyloid and small vessel disease (SVD) burden on longitudinal cognitive decline in patients with subcortical vascular dementia (SVaD).
METHODS
A longitudinal cohort study was conducted involving patients from outpatient clinics of 2 tertiary referral centers. Sixty-one patients with SVaD were prospectively recruited and underwent MRI, 11C-Pittsburgh compound B (PiB) PET at baseline, and a 3-year annual neuropsychological follow-up. Effects of PiB positivity and SVD markers (white matter hyperintensities [WMH], lacunes, and microbleeds) on longitudinal cognitive decline were evaluated using generalized estimation equation after controlling for age, sex, education, APOE4 allele, and follow-up interval.
RESULTS
When individual neuropsychological tests were used as outcome measures, PiB positivity was associated with faster cognitive decline in attention, visuospatial, visual memory, and global cognition function. Higher WMH burden was associated with faster cognitive decline in attention, visuospatial, visual recognition memory, and semantic/phonemic fluency function, whereas lacunes and microbleeds had no significant effects. When global dementia rating (Clinical Dementia Rating sum of boxes) was considered as an outcome measure, however, only PiB positivity was associated with faster cognitive decline. Significant interactions between PiB positivity and higher SVD burden were found to affect cognitive decline in semantic word fluency (from WMH burden) and global dementia rating (from microbleed burden).
CONCLUSIONS
In SVaD patients, amyloid burden, independently or interactively with SVD, contributed to longitudinal cognitive decline. Amyloid deposition was the strongest poor prognostic factor.
目的
确定淀粉样蛋白和小血管疾病（SVD）负担对皮质下血管性痴呆（SVaD）患者纵向认知衰退的独立及协同作用。
方法
进行了一项纵向队列研究，纳入来自2个三级转诊中心门诊的患者。前瞻性招募了61例SVaD患者，在基线时进行了MRI、11C-匹兹堡化合物B（PiB）PET检查，并进行了为期3年的年度神经心理学随访。在控制年龄、性别、教育程度、APOE4等位基因和随访间隔后，使用广义估计方程评估PiB阳性和SVD标志物（白质高信号[WMH]、腔隙和微出血）对纵向认知衰退的影响。
结果
当将个体神经心理学测试作为结局指标时，PiB阳性与注意力、视觉空间、视觉记忆和整体认知功能的更快认知衰退相关。较高的WMH负担与注意力、视觉空间、视觉识别记忆和语义/音素流畅性功能的更快认知衰退相关，而腔隙和微出血则无显著影响。然而，当将整体痴呆评定（临床痴呆评定框总和）作为结局指标时，只有PiB阳性与更快的认知衰退相关。发现PiB阳性与较高的SVD负担之间存在显著交互作用，影响语义单词流畅性（来自WMH负担）和整体痴呆评定（来自微出血负担）的认知衰退。
结论
在SVaD患者中，淀粉样蛋白负担独立或与SVD相互作用导致纵向认知衰退。淀粉样蛋白沉积是最强的不良预后因素。
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