背景:MRI上可见的白质高强度(WMH)体积增加是阿尔茨海默病(AD)的常见发现。我们假设临床前AD中的WMH与表现为微出血(MCH)的晚期血管淀粉样变性有关。
目的:1)评估基线WMH体积与基线MCH之间的关系。2)评估A4试验双盲阶段纵向WMH积累与末次MRIMCH之间的关系。
方法:多中心,随机化,双盲,安慰剂对照,在临床前AD患者中,在4.5年内,每4周一次输注solanezumab与安慰剂进行比较的3期研究。定义为在临床上明显的认知障碍阶段之前有脑淀粉样蛋白升高的证据,具有可选的开放标签扩展期限。
方法:抗淀粉样蛋白治疗无症状阿尔茨海默病(A4)研究。
方法:1157名认知未受损的老年人(平均年龄=71.9岁[SD=4.8岁],59%的妇女,59%APOEε4携带者)。
方法:使用线性回归模型来评估基线MCH量(0、1、2)对WMH体积的影响。线性混合效应模型用于评估末次MRIMCH对纵向WMH的影响。所有模型都校正了年龄,性别,灰质体积,皮质淀粉样蛋白PET,APOEε4状态,和治疗组。
结果:与没有MCH的个体相比,具有一个以上MCH的个体的基线WMH体积更大(t=4.8,p<0.001)。在最后一次MRI中,具有一个(t=2.3,p=0.025)和一个以上MCH(t=6.7,p<0.001)的个体中WMH的纵向增加大于没有MCH的个体。
结论:这些结果表明WMH和MCH之间有很强的关联,脑淀粉样血管病和ARIA-H的常见表现这些结果表明,增加的WMH体积可能代表血管淀粉样变性的早期迹象,可能在MCH出现之前。
BACKGROUND: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer\'s disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as
microhemorrhages (MCH).
OBJECTIVE: 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial.
METHODS: A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period.
METHODS: Anti-Amyloid Treatment in Asymptomatic Alzheimer\'s Disease (A4) study.
METHODS: A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers).
METHODS: A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group.
RESULTS: Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH.
CONCLUSIONS: These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.