载脂蛋白 E、思维障碍和 SPARE-AD 可预测已确诊帕金森病患者的认知能力下降。
APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease.
机构信息
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
Mov Disord. 2018 Feb;33(2):289-297. doi: 10.1002/mds.27204. Epub 2017 Nov 23.
BACKGROUND
People with PD are at high risk of developing cognitive impairment and dementia. Cross-sectional studies have identified candidate biomarkers associated with cognitive decline. However, longitudinal studies on this topic are rarer, and few have investigated the use of biomarker panels encompassing multiple modalities. The objective of this study was to find baseline predictors of cognitive decline in longitudinally followed, nondemented Parkinson's disease patients.
METHODS
We performed a prospective cohort study of 100 PD patients with a median disease duration of 6.4 years. All participants were nondemented at baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical, and MRI-based imaging modalities for their association with longitudinal cognitive decline for up to 8 years. We investigated biomarkers individually, as well as in a multivariate linear mixed-effects model encompassing multimodal biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the primary outcome. Annual consensus process-derived cognitive diagnosis was used for Cox proportional hazards modeling of risk for cognitive decline.
RESULTS
In multivariate analysis, the presence of the APOE E4 allele, thought disorder, and an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality for recognition of early Alzheimer's disease index) best predicted cognitive decline, with APOE E4 genotype exerting the greatest effect. The presence of the APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P < 0.05). The APOE genotype effect was not specific to any Mattis Dementia Rating Scale-2 domain.
CONCLUSIONS
Our results confirm the importance of Alzheimer's disease biomarkers as risk factors for cognitive decline in established Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.
背景
帕金森病（PD）患者发生认知障碍和痴呆的风险较高。横断面研究已经确定了与认知能力下降相关的候选生物标志物。然而，关于这一主题的纵向研究较少，而且很少有研究调查涵盖多种模式的生物标志物组合的使用。本研究的目的是在纵向随访的非痴呆帕金森病患者中寻找认知下降的基线预测因子。
方法
我们对 100 名 PD 患者进行了前瞻性队列研究，中位疾病持续时间为 6.4 年。所有患者在基线时均未出现痴呆。我们检查了来自临床、遗传、生化和基于 MRI 的成像模式的 16 种基线生物标志物，以了解其与纵向认知能力下降的关系，随访时间最长可达 8 年。我们单独检查了生物标志物，以及纳入多模态生物标志物的多变量线性混合效应模型，以随时间变化的 Mattis 痴呆评定量表-2 （Mattis Dementia Rating Scale-2）变化作为主要结局。使用年度共识过程衍生的认知诊断对认知下降的风险进行 Cox 比例风险建模。
结果
在多变量分析中，APOE E4 等位基因的存在、思维障碍和阿尔茨海默病样脑萎缩（识别早期阿尔茨海默病指数的异常空间模式）最佳预测认知下降，APOE E4 基因型的影响最大。APOE E4 等位基因的存在与认知诊断恶化的风险增加 3.5 倍相关（HR，3.53；95%CI，1.52-8.24；P<0.05）。APOE 基因型的影响并非特定于任何 Mattis 痴呆评定量表-2 域。
结论
我们的结果证实了阿尔茨海默病生物标志物作为既定帕金森病认知下降风险因素的重要性。© 2017 国际帕金森病和运动障碍学会。
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