Ding Jie, Sigurðsson Sigurður, Jónsson Pálmi V, Eiriksdottir Gudny, Charidimou Andreas, Lopez Oscar L, van Buchem Mark A, Guðnason Vilmundur, Launer Lenore J
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
Icelandic Heart Association, Kopavogur, Iceland.
JAMA Neurol. 2017 Sep 1;74(9):1105-1112. doi: 10.1001/jamaneurol.2017.1397.
With advancing age, an increased visibility of perivascular spaces (PVSs) on magnetic resonance imaging (MRI) is hypothesized to represent impaired drainage of interstitial fluid from the brain and may reflect underlying cerebral small vessel disease (SVD). However, whether large perivascular spaces (L-PVSs) (>3 mm in diameter) visible on MRI are associated with SVD and cognitive deterioration in older individuals is unknown.
To examine whether L-PVSs are associated with the progression of the established MRI markers of SVD, cognitive decline, and increased risk of dementia.
DESIGN, SETTING, AND PARTICIPANTS: The prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study assessed L-PVSs at baseline (September 1, 2002, through February 28, 2006) on MRI studies of the brain in 2612 participants. Participants returned for additional MRI from April 1, 2007, through September 30, 2011, and underwent neuropsychological testing at the 2 time points a mean (SD) of 5.2 (0.2) years apart. Data analysis was conducted from August 1, 2016, to May 4, 2017.
The presence, number, and location of L-PVSs.
Incident subcortical infarcts, cerebral microbleeds, and progression of white matter hyperintensities detected on MRI; cognitive decline defined as composite score changes between baseline and follow-up in the domains of memory, information processing speed, and executive function; and adjudicated incident dementia cases diagnosed according to international guidelines.
Of the 2612 study patients (mean [SD] age, 74.6 [4.8] years; 1542 [59.0%] female), 424 had L-PVSs and 2188 did not. The prevalence of L-PVSs was 16.2% (median number of L-PVSs, 1; range, 1-17). After adjusting for age, sex, and interval between baseline and follow-up scanning, the presence of L-PVSs was significantly associated with an increased risk of incident subcortical infarcts (adjusted risk ratio, 2.54; 95% CI, 1.76-3.68) and microbleeds (adjusted risk ratio, 1.43; 95% CI, 1.18-1.72) and a greater 5-year progression of white matter hyperintensity volume. The presence of L-PVSs was also associated with a steeper decline in information processing speed and more than quadrupled the risk of vascular dementia. All associations persisted when further adjusted for genetic and cerebrovascular risk factors. The associations with cognitive outcomes were independent of educational level, depression, and other SVD MRI markers.
Large PVSs are an MRI marker of SVD and associated with the pathogenesis of vascular-related cognitive impairment in older individuals. Large PVSs should be included in assessments of vascular cognitive impairment in the older population and as potential targets for interventions.
随着年龄增长，磁共振成像（MRI）上血管周围间隙（PVS）的可视性增加被认为代表脑间质液引流受损，可能反映潜在的脑小血管疾病（SVD）。然而，MRI上可见的大血管周围间隙（L-PVS，直径>3mm）是否与老年人的SVD和认知衰退相关尚不清楚。
研究L-PVS是否与SVD既定的MRI标志物进展、认知衰退及痴呆风险增加相关。
设计、背景和参与者：前瞻性、基于人群的年龄、基因/环境易感性-雷克雅未克研究在2612名参与者的脑部MRI研究中于基线期（2002年9月1日至2006年2月28日）评估L-PVS。参与者于2007年4月1日至2011年9月30日再次接受MRI检查，并在平均（标准差）间隔5.2（0.2）年的两个时间点接受神经心理学测试。数据分析于2016年8月1日至2017年5月4日进行。
L-PVS的存在、数量和位置。
MRI检测到的新发皮质下梗死、脑微出血和白质高信号进展；认知衰退定义为记忆、信息处理速度和执行功能领域基线与随访之间的综合评分变化；以及根据国际指南判定的新发痴呆病例。
2612名研究患者（平均[标准差]年龄74.6[4.8]岁；1542名[59.0%]为女性）中，424名有L-PVS，2188名没有。L-PVS的患病率为16.2%（L-PVS中位数为1；范围为1-17）。在调整年龄、性别以及基线与随访扫描之间的间隔后，L-PVS的存在与新发皮质下梗死风险增加（调整风险比，2.54；95%CI，1.76-3.68）和微出血（调整风险比，1.43；95%CI，1.18-1.72）以及白质高信号体积5年更大进展显著相关。L-PVS的存在还与信息处理速度更急剧下降相关，且血管性痴呆风险增加四倍多。在进一步调整遗传和脑血管危险因素后，所有关联均持续存在。与认知结局的关联独立于教育水平、抑郁和其他SVD MRI标志物。
大PVS是SVD的MRI标志物，与老年人血管相关认知障碍的发病机制相关。大PVS应纳入老年人群血管性认知障碍的评估，并作为潜在的干预靶点。
