基于OCT-RNFL的MCI-AD个体化筛查模型的建立和验证

Early screening of subjects who suffering high risks of deteriorating to Alzheimer's disease (AD) in MCI (MCI-AD) is the key point of prevention for dementia. Retinal nerve fiber layer (RNFL) through optical coherence tomography (OCT) may reflect neuropathological change of AD in a rapid and non-invasive way, which in applicable in community screening. Our preliminary investigation showed that thickness of RNFL decreased significantly in MCI than cognitively normal subjects. The value of RNFL in screening MCI-AD need to be further investigated through prospective study. We use reciever operating characteristic (ROC) curve generalized lineat model to build the best individualized model based on OCT-RNFL index for screening MCI-AD. The validity and reliability of this OCT-RNFL based model in judging MCI-AD is dynamically inspected via correlation between model and cognitive-behavior as well brain imaging index in 18 months' follow-up period. This model may be one of sensitive,reliable and practicable measure of screening high-risk sbjects of AD in community. And the role of optic nurve-visual cortex-visual spatial network pathyway in the neural machanisms of MCI-AD will be futher investigated. It may help to provide scientific prove of this model in screening MCI-AD subjects.

早期诊断轻度认知功能损害中罹患老年性痴呆（AD）风险高的个体（MCI-AD）是痴呆二级预防的关键。光学相干断层扫描（OCT）对视神经纤维层（RNFL）结构的识别能反映AD的神经病理状态，且快速无创，适于社区大样本的筛查。基于我们前期证实的MCI RNFL厚度较对照组显著减少的研究基础，本研究进一步开展RNFL参数对MCI-AD敏感性的前瞻性分析。利用受试者工作特征曲线广义线性模型建立基于OCT-RNFL的MCI-AD的最优个体化筛查模型，并在18个月随访期内动态检验该模型对MCI-AD判别的敏感性和可靠性。同时对筛查获得MCI-AD个体的视神经纤维形态与视皮质/皮质网络功能的相关性进行深入分析，初步研究"视神经-视皮质-视空间网络"通路在MCI-AD神经病理机制中的作用，探索基于OCT-RNFL的个体化模型有效筛查MCI-AD的科学依据。

阿尔茨海默病（AD）是老年期痴呆最常见的类型，其所致精神行为障碍给社会和家庭带来了巨大负担。临床期AD至今仍缺乏有效治疗，现有药物、疫苗等均不能改善疾病预后，早期诊断AD是对其干预最关键的环节和最有效的措施。因此，探索和建立敏感高效的生物标记具有重要的临床价值。课题组前期通过光学相干断层扫描（OCT）发现轻度认知功能障碍（MCI）患者视网膜的视神经纤维层退化（RNFL-C）。基于此，本项目开展了一项较大规模为期25个月的前瞻性队列研究，随访评估社区老人认知功能变化、观察OCT-RNFL的变化规律以及头颅MRI-海马萎缩情况，建立“基于OCT-RNFL 的MCI-AD 的个体化筛查模型”， 并探索RNFL-C对于认知功能转化的预测价值（Front Cell Neurosci 2013, Curr Alzheimer Res 2014, J Alzheimers Dis 2014&2015）；同时通过与AD经典影像学生物标记MRI-海马萎缩的比对，以验证OCT-RNFL的有效性和可行性（研究结果待发表）。此外，本项目采集了手术患者脑脊液（CSF）标本，分析OCT-RNFL与Aß沉积或tau磷酸化的关联，以明确AD患者RNFL退化的神经病理机制（研究结果正在整理中）。通过本项目研究，建立了经济便捷、无创可重复的AD早期筛查模型，有利于延缓和逆转AD病情进展，及时开展有效干预和治疗。