Project 1: Amyloid Imaging in Subjective Cognitive Decline

项目1：SCD摘要： 流行病学证据表明，主观记忆在衰老中的主诉 会导致认知能力下降和/或发展为痴呆症。还有就是 越来越多的证据表明，阿尔茨海默病(AD)生物标记物，包括淀粉样β蛋白(A�)病理， 与其他健康老年人的主观认知主诉相关的临床状态 被描述为主观认知下降(SCD)。在AD研究界，对SCD AS的兴趣与日俱增 潜在的最早可检测到的AD症状进一步推动了越来越早的目标 干预和二级预防试验中的风险识别。然而，临床前AD的边界转移 接近正常认知老化带来了许多挑战。主观记忆方面的投诉和担忧有 在老年人中很常见，甚至可能是正常的。到目前为止，我们缺乏有关如何执行以下操作的信息数据 最好区分主观认知主诉的病因，包括正常的认知老化。 个性特征和情绪症状的个体差异被认为是 主观认知抱怨；这些心理因素如何相互作用，以及它们是否独立于 阿尔茨海默病的潜在病理生理学机制尚不清楚。拟议项目的目标是进一步了解 关于SCD和A�病理可能是如何联系的。为了实现这一目标，我们将招募和研究56个样本 年长的志愿者在医疗环境中出现时存在记忆或其他认知方面的担忧 下降，但谁也有正常的客观测试表现。我们将检验SCD是 与匹兹堡化合物B(PIB)评估的A�阳性个体的较高比例有关- PET成像，与年龄和教育程度匹配的认知正常对照组进行比较 担忧。此外，我们假设�阳性(与�阴性相比)的SCD将与1相关。 问卷测量的变量，包括人格特征“情绪不稳定”(即“神经质”)， 情景记忆主诉和日常生活中的功能障碍程度；以及2)其他AD生物标志物变量 反映大脑变化，包括结构和功能磁共振，以及更具挑战性的细微缺陷 认知测试。在可能的程度上，探索性目标是比较轻度认知障碍的发生率。 作为基线A�状态的函数，通过临床核心随访来评估损害。该项目将提供 为进一步的纵向研究奠定基础，长期目标是确定哪些生物标记物和 SCD的心理特征预示着临床进展为MCI和AD。本项目的调查结果 将进一步告知模型AD-病理生理序列与非常早期的行为和 症状性变化。

Project 1: SCD Abstract: Epidemiologic evidence suggests that subjective memory complaints in aging confer some degree of risk for subsequent cognitive decline and/or progression to dementia. There is also accumulating evidence that Alzheimer Disease (AD)-biomarkers, including amyloid-beta (A�) pathology, are associated with subjective cognitive complaints in otherwise healthy older individuals a clinical state described as Subjective Cognitive Decline (SCD). In the AD research community, growing interest in SCD as potentially the earliest detectable symptoms of AD is further fueled by the goal of increasingly earlier identification of risk in intervention and secondary prevention trials. However, a boundary shift of preclinical AD closer toward normal cognitive aging poses many challenges. Subjective memory complaints and concerns are common, perhaps even normative, among older adults. To date, we lack informative data addressing how to best to distinguish among etiologies of subjective cognitive complaints, including normal cognitive aging. Individual differences in personality traits and mood symptoms are known to be important correlates of subjective cognitive complaints; how these psychological factors interact and whether they are independent of underlying AD pathophysiology is not yet understood. The goal of the proposed Project is to further knowledge about how SCD and A� pathology may be associated. To achieve this, we will recruit and study a sample of 56 older volunteers who have presented in a medical setting with concerns about memory or other cognitive decline, but who also have normal objective test performance. We will test the hypothesis that SCD is associated with a higher proportion of A�-positive individuals, as assessed by Pittsburgh compound B (PiB)- PET imaging, compared to age- and education-matched cognitively normal controls without presenting concerns. Further, we hypothesize that A�-positive (compared to A�-negative) SCD will be associated with 1) questionnaire-measured variables, including the personality trait `emotional instability (i.e.,`neuroticism'), episodic memory complaints and degree of dysfunction in daily life; and 2) other AD-biomarker variables reflective of brain changes, including structural and functional MRI, and subtle deficits on more challenging cognitive tests. To the degree possible, an exploratory aim is to compare rates of incident mild cognitive impairment (MCI) through Clinical Core follow-up, as a function of baseline A� status. This Project will provide the foundation for further longitudinal study, with the longer-term goal of determining which biomarker and psychological features of SCD are predictive of clinical progression to MCI and AD. Findings from this Project will further inform models of the AD-pathophysiological sequence in relation to very early behavioral and symptomatic change.