恢复期老年抑郁症伴发aMCI患者向AD转化的风险评估及预警研究

Late-life depression (LLD) and Alzheimer's disease (AD) are the two major diseases that influence the health of the elderly.28.5% remitted late-life depression patients met the diagnostic criteria of amnestic mild cognitive impairment (aMCI) simultaneously. LLD and aMCI are both independent risk factors for AD. Individuals with LLD and aMCI (LLD+aMCI) are at a markedly increased risk of converting to AD. However, we have no idea how to identify individuals at high risk for AD. In our preliminary work, we found that pathophysiological processes underlying depression, including decreased levels of BDNF, increased levels of cortisol and proinflammatory factors are significantly associated with cognitive impairment of patients with LLD+aMCI. We intend to perform a longitudinal, 3-year follow-up cohort study in patients with remitted LLD+aMCI. We are going to detect the effective predictors according systematic screen for risk factors that may affect the cognitive outcome of LLD and aMCI , including clinical characteristics, cognitive impairment, genetics, pathophysiological factors of depression associated with cognitive impairment, the volume of the hippocampus and metabolite levels of hippocampus. Then we will establish risk evaluation system and forewarning model for LLD+aMCI converting to AD. This study will provide new strategy for risk assessment and early identification of high-risk AD patients from LLD+aMCI individuals. It is significant for improvement of the elderly health status and reducing disease burden.

老年抑郁症（LLD）和阿尔茨海默病（AD ）是危害老年人健康的重大疾病。LLD进入恢复期后有28.5%的患者同时符合遗忘型轻度认知障碍（aMCI）的诊断。LLD和aMCI均为AD的独立危险因素，当LLD患者伴发aMCI（LLD+aMCI）时，转化为AD的风险显著增高，但目前仍无法识别其中的高危者。本项目前期研究发现，抑郁的病理生理变化，如低BDNF、高皮质醇及高促炎因子水平与LLD+aMCI认知损害密切相关。本项目拟建立恢复期LLD+aMCI患者队列，进行3年随访研究，从影响LLD和aMCI认知结局的因素进行系统筛查（包括临床特征、神经心理、遗传、抑郁相关的导致认知损害的因素、海马神经影像特征），以筛选出敏感指标体系，建立LLD+aMCI转化为AD的风险评估系统及预警模型。本研究将为LLD+aMCI患者的AD风险评价及高危者的早期识别提供有效方法，对促进老年人健康、减轻疾病负担有重要意义。

老年抑郁症（LLD）和阿尔茨海默病（AD）是危害老年人健康的重大疾病，给社会发展带来沉重的疾病负担。当LLD伴发认知功能障碍时，转化为痴呆的风险显著增高，但目前仍无法识别其中的高危者。本研究通过构建LLD患者序列，进行3年随访研究，建立包括临床特征、遗传、神经心理、体液指标、神经影像、嗅觉、电生理多指标数据库。本研究发现：（1）LLD进入恢复期后仍有34%的患者同时MCI诊断，3年随访后，46.5%的患者出现痴呆风险增高；（2）LLD伴有认知功能下降是痴呆的高风险人群；（3）痴呆高风险组的LLD患者年龄更大、受教育程度更低、情绪低落持续时间更长、认知功能受损更明显、血浆胆固醇水平下降；（2）血清皮质醇水平、双侧海马灰质体积、嗅觉识别得分、正性EMMN波幅可有效预测LLD患者痴呆风险增高；（3）通过探寻预测LLD患者痴呆风险增高的独立风险指标，共筛选出13个敏感指标体系，指标组合预测痴呆风险增高的准确率达82.1%。（4）将13个敏感指标纳入Cox回归模型，最终筛选出包括受教育年数、情绪低落持续时间、HAMD-17项总分、胱抑素水平、胆固醇水平、神经心理测评中记忆、视空间领域得分的7个变量，构建Cox比例风险回归模型。（5）采用支持向量机的方法，构建数学预警模型，预测LLD痴呆风险增高的准确率达86.36%。本研究为LLD患者痴呆风险增高评价及高危者的早期识别提供有效方法，对促进老年人健康、减轻疾病负担具有重要意义。