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从轻度认知障碍到阿尔茨海默病的转化时间的多变量模型。

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

机构信息

Department of Experimental Psychology, Cognitive Processes and Speech Therapy, Complutense University of Madrid, Madrid, Spain.

Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Polytechnic University of Madrid, Madrid, Spain.

出版信息

Geroscience. 2020 Dec;42(6):1715-1732. doi: 10.1007/s11357-020-00260-7. Epub 2020 Sep 4.

Abstract

The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the "progressive" MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) the "stable" MCI group (n = 75; mean time of follow-up 31.37 ± 14.58 months). Kaplan-Meier survival analyses were applied to explore each variable's relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were "unfavorable" (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.

摘要

本研究旨在确定哪些人口统计学、遗传学、认知、神经生理学和神经解剖因素的组合可能预测从轻度认知障碍 (MCI) 到阿尔茨海默病 (AD) 的进展时间的差异。为此,对 121 名 MCI 患者进行了为期 5 年的随访。根据他们的临床结果,MCI 被分为两个亚组:(i)“进展性”MCI 组(n=46;平均进展时间 17±9.73 个月)和 (ii)“稳定”MCI 组(n=75;平均随访时间 31.37±14.58 个月)。应用 Kaplan-Meier 生存分析探讨每个变量与向 AD 进展的关系。一旦发现潜在的预测因素,就会使用 Cox 回归分析来计算一个简约模型来估计进展时间的差异。最终模型包括三个变量(按相关性顺序排列):左海马旁回体积(校正颅内体积后,LP_ICV)、延迟回忆(DR)和左枕下回个体 alpha 峰值频率(LIOL_IAPF)。那些 LP_ICV 体积、DR 评分和 LIOL_IAPF 值低于定义的截值的 MCI 患者,向 AD 进展的风险分别高出 6 倍、5.5 倍和 3 倍。此外,当三个变量的类别为“不利”(即低于截值)时,100%的病例在随访结束时进展为 AD。我们的结果强调了神经生理学标志物作为转化预测因子(LIOL_IAPF)的相关性,以及结合不同性质标志物的多变量模型对预测从 MCI 到痴呆的进展时间的重要性。

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