载脂蛋白E基因型对老年认知损伤转归影响的队列研究

China is a country with the world's largest, fast-growing old population, as well as a dementia risk country. Mild cognitive impairment is the early manifestation of dementia, therefore, the study on senile mild cognitive impairment prognosis and influencing factors is of great significance on the early prevention of dementia. At present, the Alzheimer's research lacks population-based cohort follow-up, and early intervention research. This topic is a population cohort study based on the combined research of field investigation and laboratory testing, the basic research and applied interventions, as well as the biological and psychosocial factors, with the purpose to study different genotypes in elderly patients with cognitive impairment outcomes, and to study a variety of family and social factors on senile cognitive impairment prognosis. In particular, this research, through 4-year follow-up study, focuses on different genotypes of age-related cognitive impairments in the natural prognosis and intervention effect with and without intervention, to reveal the effects of senile cognitive impairment prognosis factors, especially the apolipoprotein E genotype on elderly patients with cognitive impairment prognosis influence. This is the main innovation and feature of this study. The research provides scientific basis for the further development of senile dementia early intervention, and has vital significance and practical value in seeking effective ways concerning prevention and control on senile dementia.

我国是世界上老年人口最多、增长最快的国家之一,也是老年痴呆症的高危国家。轻度认知功能损伤是老年痴呆的早期表现，研究老年轻度认知功能损伤转归及影响因素,对早期预防老年痴呆具有重要意义。目前，针对老年痴呆的研究，缺乏人群队列随访，缺乏早期非药物干预研究。本课题在人群队列研究的基础上，把现场调查与实验室检测相结合，把基础研究与应用干预相结合，把生物与社会心理因素相结合，研究不同基因型老年认知功能损伤转归，研究各种家庭社会因素对老年认知损伤转归的影响，特别是通过4年随访，研究在有、无干预两种情况下不同基因型的老年认知损伤的自然预后和干预效果，阐明影响老年认知功能损伤转归的因素，特别是载脂蛋白E基因型对老年认知功能损伤转归的影响程度，这是本课题主要创新点和特色。本课题的研究为进一步开展老年痴呆早期干预提供科学依据，对寻找预防和控制老年痴呆发生的有效途径具有重要意义和实用价值。

本课题为了解老年人中Apo E基因型的分布情况,分析Apo EE4基因型与老年认知损伤的关系态势老年认知损伤的危险因素。随机选取老年人546例,根据MoCA Version量表测评的内容，进行老年认知损伤的早期筛查,分离其白血细胞基因组DNA,用PCR技术扩增Apo E带有多态性位点，检测其基因型。并对189例轻度认知功能损伤老年人和正常老年人进行病例对照研究，采用logistic分析方法，研究轻度认知功能损伤的危险因素。结果发现在老年人群中,Apo EE3/3为最常见的基因型,而E2/2最少见。在认知损伤的老人中,Apo EE4等位基因频率明显高于对照组(P<0105),Apo EE4与老年认知损伤的相关；logistic分析发现，体力劳动者、离异丧偶、独居、高血压、糖尿病、与子女关系淡漠、抑郁倾向、携带Apo EE4基因是老年人MCI发生的危险因素，较高月收入、坚持体育锻炼是MCI发生保护因素。本研究结果表明需要加强对Apo EE4老年人及有危险因素的老年人进行早期干预，预防痴呆的发生。