数字化语言标志物区分阿尔茨海默病和轻度认知功能障碍的疾病效应与老化效应初探

Digital language markers distinguish the pathological effect of Alzheimer′s disease and mild cognitive impairment from the aging effect

目的分析阿尔茨海默病(AD)和轻度认知功能障碍(MCI)患者的数字化语言标志物特点,并探讨数字化语言标志物对于区分AD和MCI患者疾病效应和老化效应的意义。方法纳入北京协和医院认知障碍门诊临床诊断的AD患者14例、MCI患者16例,同时纳入年龄、性别、教育水平相当的认知正常的18名老人及19名青年人作为对照组。采集动物流畅性测验电子语音数据,在传统产词量、聚类和转换指标的基础上加入反应时间、语义相似度和词频等新的评估指标进行分析。统计方法采用多重线性回归分析,采用强迫进入法进行回归模型的检验。结果多重回归分析结果表明,在控制了教育年限后,4组间在11个指标(除后15 s有效产词量、串联总数、首词反应时间、平均语义相似度外)上均差异有统计学意义(均P<0.001)。与其余3组相比,AD组在有效产词量、有效率、重复率、前15 s有效产词量、亚类数、单个词产出时间和亚类间转换间隔上均差异有统计学意义(均P<0.001)。此外,与认知正常青年组相比,AD组转换次数显著减少,语义最大距离显著缩短(P=0.001,P<0.001);AD和MCI组的亚类内转换间隔均显著延长(P<0.001,P=0.001);AD组、MCI组和认知正常老年组的词频均显著增高(均P<0.001);MCI组的有效产词量和亚类数显著减少(P=0.002,P=0.003);MCI和认知正常老年组的单个词产出时间均显著延长(均P<0.001)。结论AD患者在语义流畅性测验任务上的表现不仅受到病理的影响,也受到正常老化的影响以及两者的共同作用。病理指标包括:有效产词量、有效率、重复率、前15 s有效产词量、亚类数、亚类间转换间隔以及单个词产出时间。这些结果为鉴别AD特异性效应提供了新的思路。

Objective To characterize the digital language markers in Alzheimer′s disease (AD) and mild cognitive impairment (MCI) patients, and to explore the pathological effect and aging effect on these markers.Methods AD (n=14) and MCI (n=16) patients from memory clinic in Peking Union Medical College Hospital, age-matched cognitively normal elderly adults (n=18) and youthful adults (n=19) as controls participated in the study. The digital speech data of animal fluency test were collected. Novel language markers such as response time, semantic similarity and word frequency were analyzed in addition to the traditional word production, clustering and switching indicators by trained professionals. Multiple linear regression analysis with multiple comparison was used to test the associations of language markers with the cognitive status, adjusting for education.Results The results of multiple regression analysis showed that, after adjusting for the years of education, statistically significant differences existed in 11 language markers among the four groups (P<0.001), except for the effective word production in the last 15 s, cluster size, the first word response time and the average semantic similarity. Compared to other three groups, AD group differed significantly in effective word production, effective rate, repetitive rate, effective word production in the first 15 s, the number of subcategories, single word production time and inter-subcategory switching interval (P<0.001). In addition, compared to cognitively normal youthful group, AD group had less number of switching and shorter semantic maximum distance (P=0.001, P<0.001);both AD and MCI groups had longer intra-subcategory switching interval (P<0.001, P=0.001);AD, MCI and cognitively normal elderly groups had significantly higher word frequency (P<0.001);MCI group had significantly less number of effective word production and subcategories (P=0.002, P=0.003);both MCI and cognitively normal elderly groups had significantly longer single word production time (P<0.001).Conclusions The performance of AD patients on the semantic fluency test task was affected by both pathological effect and normal aging effect. Pathological indicators included effective word production, effective rate, repetition rate, effective word production in the first 15 s, the number of subcategories, inter-subcategory switching interval and single word production time. These results provide a new approach to identify the specific effects of AD dementia.