"RISK FACTORS AND STAGES OF COGNITIVE DECLINE"

该项目的目标是澄清从正常状态到明确定义的中间状态以及从中间状态到阿尔茨海默病（AD）或AD和血管性痴呆（AD/VaD）的认知转变，以及影响这些转变的风险因素和保护因素。AD和AD/VaD的发展分为3个阶段，可以使用变点模型进行回顾性识别：相对认知稳定阶段，加速认知衰退阶段和临床痴呆阶段。基于理论上的考虑，我们已经开发和测试了两个预期的操作定义， 认知障碍的中间状态。第一种是记忆性认知障碍（ACI）， 患病率为21%，是我们样本中遗忘型轻度认知障碍（MCI）患病率的4倍多，并与10%的年痴呆转化率相关。第二，不太好的中间阶段，非遗忘性认知障碍（NACI）的患病率为15%。这些结构扩大了预防干预的潜在对象库。此外，新出现的证据表明，AD和AD/VaD的危险因素的影响可能取决于疾病的阶段。该项目建议在疾病阶段模型的背景下评估五类风险因素。风险因素类别包括可改变的心血管风险因素、临床和神经心理学指标， 社会人口统计学和选择的行为测量、生物标志物（炎症、血栓形成、脂质谱和血浆Abeta）以及神经成像。最终，这项研究应有助于将流行病学研究转化为临床试验和公共卫生实践，更好地定义导致痴呆症的中间状态，并在与一级和二级预防模型相关的框架内评估风险因素。

The goal of the project is to clarify the cognitive transitions that lead from normality to well-defined intermediate states and from intermediate states to Alzheimer's Disease (AD) or AD and Vascular Dementia (AD/VaD) as well as the risk factors and protective factors that influence those transitions. AD and AD/VaD develop in 3 stages which can be retrospectively identified using change point models: a stage of relative cognitive stability, a stage of accelerated cognitive decline and a stage of clinical dementia. Based on theoretical considerations, we have developed and tested two prospective operational definitions for intermediate states of Cognitive Impairment. The first, Anmestic Cognitive Impairment (ACI) has a prevalence of 21%, more than 4 times the prevalence of amnestic Mild Cognitive Impairment (MCI) in our sample, and is associated with a 10% annual conversion rate to dementia. A second, less well characterized intermediate stage, Nonamnestic Cognitive Impairment (NACI) has a prevalence of 15%. These constructs expand the pool of potential subjects for preventive interventions. In addition, emerging evidence suggests that the influence of risk factors on AD and AD/VaD may depend upon the stage of illness. This project proposes to assess five categories of risk factors in the context of a stage of illness model. Risk factor categories include modifiable cardiovascular risk factors, clinical and neuropsychological measures, sociodemographic and selected behavioral measures, biological markers (inflammation, thrombosis, lipid profiles and plasma Abeta) as well as neuroimaging. Ultimately, this research should facilitate the translation of epidemiologic research into clinical trials and public health practice by better defining the intermediate states that lead to dementia and assessing risk factors in a framework tied to models of primary and secondary prevention.