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AD 相关基因(APOE 和TOMM40)和血管风险因子对社区老年人认知功能的影响
其他题名The Effects of AD-related Genes (APOE and TOMM40) and Vascular Risks on Cognition in Community-dwelling Older Adults
侯剑华
学位类型硕士
导师李娟
2017-04
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业发展与教育心理学
关键词老年人 认知 载脂蛋白E 基因(APOE) 线粒体跨外膜转位酶40 基 因(TOMM40) 血管风险
摘要

目的:老年人认知功能随着年龄的增长而逐渐衰退。老年人认知功能的衰退严重影响到他们的日常功能,而且还造成严重的经济负担。有大量研究表明,老年人认知功能的衰退除了增龄的影响外,还受到大量其他风险因素的影响,包括携带痴呆风险基因,血管风险因素以及不良的生活方式等。因此识别和探索这些风险因素影响社区老年人认知衰退的模式是至关重要的公共卫生议题。淀粉样蛋白沉积是伴随着老化过程而产生的重要生物标志物,它不仅仅存在于AD 患者病理过程中,还存在于健康老年人的老化过程中。APOE、TOMM40 和血管风险因素在淀粉样蛋白产生和清除过程中起重要作用。同时大量临床研究发现,淀粉样蛋白的沉积过程与认知功能的进行性变化也密切相关。本研究采用纵向前瞻设计,探讨了AD 相关基因(APOE 和TOMM40)以及血管风险因子对社区老年人基线认知以及认知功能随时间衰退的影响。
方法:本研究在北京三个市辖区的老年人当中随机取样,总共包含365 名被试纳入到基线分析。采用纵向前瞻设计,对社区老年人进行人口学调查、神经心理学测验、血生化测验、情绪情感测验、临床医师评定和基因分型,通过对不同时间点的比较,考察AD 相关基因(APOE 和TOMM40)和血管风险因子对社区老年人基线认知功能以及认知功能随时间衰退的影响。
结果:在控制年龄、性别、受教育程度以及抑郁得分后,对基线认知功能分析发现:(1)数字倒背测验: APOE 和血管风险因素存在交互作用,即在APOE风险基因存在的时候,血管风险因子与测验成绩显著负相关,在APOE 风险基因不存在的时候,血管风险因子与测验成绩无显著相关。(2)联想学习测验:APOE和血管风险因素的交互作用存在,即在APOE 风险基因存在的时候,血管风险因子与测验成绩显著负相关,在APOE 风险基因不存在的时候,血管风险因子与测验成绩无显著相关。(3)对于其他认知领域,没有发现基因-血管风险对基线测验成绩有显著影响;同样在控制年龄、性别、受教育程度以及抑郁得分后对追踪数据的分析发现:(1)数字倒背测验:APOE 和血管风险因素存在主效应,即与APOE 风险基因非携带者相比,携带者的数字倒背测验成绩衰退越快;与低血管风险因素组相比,高血管因素风险被试成绩衰退越快。(2)联想学习测验:APOE和血管风险因素的交互作用存在,即在APOE 风险基因存在的时候,血管风险因子与测验成绩变化显著负相关,在APOE 风险基因不存在的时候,血管风险因子与测验成绩变化无显著相关。(3)对于其他认知领域,没有发现基因-血管风险对测验成绩的衰退有显著影响;
结论:(1)APOE 与血管风险因子对社区老年人基线认知有影响,表现在工作记忆和联结记忆上。与未携带APOE 风险基因组相比,风险基因携带者的工作记忆和联结记忆成绩才会随着血管风险因子的增加而下降。(2) APOE 与血管风险因子对社区老年人认知衰退速率有影响,表现在工作记忆和联结记忆上。APOE 和血管风险因子独立作用于工作记忆的衰退上。而与未携带APOE 风险基因组相比,风险基因携带者联结记忆成绩衰退速率才会随着血管风险因子的增加而提高。(3)TOMM40 对社区老年人基线认知水平和认知衰退都没有影响。

其他摘要

Objective: Cognitive function gradually declines along with ageing. Numerous studies have confirmed that several risking factors, besides ageing, affect cognitive decline course, including AD-related genes, vascular risks and unhealthy lifestyle. Cognitive decline exerts great impact on quality of daily life and causes growing financial burden. So it is important to distinguish and investigate how these risking factors influence such decline process, which is a vital public health issue. Amyloid deposition is an important bio-marker, which demonstrates in the process of healthy ageing and pathological ageing. AD-related genes and vascular risking factors play key roles in amyloid deposition which is close related to cognitive ageing. Thus we adopted prospective longitudinal design to investigate the effects of AD-related genes and vascular risking factors on cognition among community-dwelling older adults.
Methods: In this study, a total of 365 community-dwelling older adults were recruited in the baseline analysis. Prospective longitudinal design was adopted to assess how AD-related genes and vascular risking factors influence the baseline of cognition and the slope of cognitive decline with the application of basic demographical information test, neuropsychological test, clinical assessment and blood sample.
Results: After controlling age, gender, years of education and CESD score, baseline results showed(1)regarding digital span(backward), significant negative association was detected between vascular risking factor and working memory performance among APOE ε4 carriers. (2)regarding associative learning test, significant negative association was also detected between vascular risking factor and associative memory performance among APOE ε4 carriers. (3)regarding the tests for other cognitive domains, no significant results were in baseline analysis. In the follow-up analysis, after controlling age, gender, years of education and CESD score, results showed (1) regarding digital span(backward), only main effect of APOE and vascular risking factor was detected. ( 2 ) regarding associative learning test, significant negative association was also detected between vascular risking factor and associative memory decline among older adults with APOE ε4. (3)regarding the tests for other cognitive domains, no significant results were in follow-up analysis. Conclusions: These results suggest(1)APOE and vascular risking factors could influence baseline working memory and associative memory performance among community-dwelling older adults. Among APOE ε4 carriers, baseline performance was negatively related to vascular risking factors. (2) APOE and vascular risking factors could influence working memory and associative memory decline rate among community-dwelling older adults. APOE and vascular risking factors independently influence the working memory decline rate. Regarding associative memory decline, the negative correlation was only found among APOE ε4 carriers. (3)It seems that TOMM40 might be irrelevant to baseline cognition and cognition decline among Chinese older adults.

语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/21497
专题认知与发展心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
侯剑华. AD 相关基因(APOE 和TOMM40)和血管风险因子对社区老年人认知功能的影响[D]. 北京. 中国科学院研究生院,2017.
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