PET AMYLOID PLAQUE IMAGING IN LATE LIFE DEPRESSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 晚年抑郁(LLD)是一种常见的、令人衰弱的问题，可能表明发生认知障碍的风险更高。我们目前的资助“血管性抑郁症的治疗结果”MH60697收集了LLD患者和对照组的大样本(n=120)和对照(n=40)，以前瞻性地检查白质疾病、脑血管危险因素和认知功能。然而，LLD是一种异质性疾病，其发展的危险因素知之甚少；血管疾病和早期痴呆都是常见的共病综合征。LLD抑郁症状实际上可能是早期痴呆的表现症状。另外，LLD可能是AD的独立危险因素。因此，早期痴呆，可能比DAT早几年，是一个可能导致不良结果的重要因素，包括LLD的治疗抵抗。 一种新的活体脑淀粉样蛋白显像剂[11C]PIB提供了确定LLD受试者是否存在脑淀粉样蛋白结合异常的机会。我们有初步数据显示，LLD患者PIB+状态增加了3倍：3/10 LLD患者与2/20对照组PIB+。另外2/5的抗抑郁药无反应者(NR)与1/5的反应者(R)PIB+。在目前的方案中，我们使用[11C]PIB的PET成像来收集初步数据，以调查与对照组相比，脑PIB结合升高是否与LLD有关，特别是在LLD治疗无效者和长期抑郁症患者中。如果这个PET数据显示支持我们的假设，我们将使用这个试点数据集作为更大的拨款申请的基础，以进一步探索这些关系。我们还从我们最初的“治疗结果”研究中获得了一些其他关键的神经成像、认知和临床数据，并将探索它们在多大程度上为LLD提供显著的预测效果。 年龄在65-85岁之间的非痴呆型LLD受试者(n=50)已经完成了一项使用标准抗抑郁药物的治疗研究，他们将被招募进行PET和[11C]PIB成像、MRI、认知测试和确定临床措施。治疗无效的抑郁症受试者(n=25)将与应答者(n=25)和非痴呆的非抑郁症对照样本(n=25)进行比较。目的1：与对照组相比，LLD受试者的灰质[11C]PIB结合量增加。目的2：与应答者相比，无应答者的灰质[11C]PIB结合量增加。目的3：探讨其他测量方法，包括终生抑郁持续时间、发病年龄和合并血管危险因素。这项研究的成功完成将允许进行效应大小和功率计算，这在设计确定LLD是否与PIB+患者数量增加有关的最终研究中至关重要。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Late life depression (LLD) is a common and debilitating problem that may indicate a higher risk for developing cognitive impairment. Our current grant "Treatment Outcome of Vascular Depression" MH60697 has gathered a large sample (n=120) of LLD patients and controls (n=40) to examine white matter disease, cerebrovascular risk factors and cognitive function prospectively. However, LLD is a heterogenous disorder with poorly understood risk factors for development; both vascular disease and incipient dementia are common comorbid syndromes. LLD depressive symptoms actually may be the presenting symptoms of incipient demenita. Alternatively, LLD may be an independent risk factor for AD. Thus, incipient dementia, perhaps years in advance of DAT, is an important factor that may contribute to poor outcome, including treatment resistance in LLD. A novel agent for imaging brain amyloid in vivo, [11C]PIB, presents the opportunity to determine whether subjects with LLD have abnormal brain amyloid binding. We have preliminary data showing a 3 fold increase in PIB + status in LLD: 3/10 LLD patients vs 2/20 controls were PIB +. Further 2/5 antidepressant non-responders (NR) vs 1/5 responders (R ) PIB+. In the current proposal, we use PET imaging of [11C]PIB to gather preliminary data to investigate whether compared with control subjects, elevated brain PIB binding will be associated with LLD, especially in LLD treatment non-responders and those with longstanding depression. If this PET data shows support for our hypothesis we will use this pilot dataset as a basis for a larger grant application to further explore these relationships. We also have a number of other key neuroimaging, cognitive and clinical data from our original "Treatment Outcome" study and will explore the extent to which they provide significant predictive effects for LLD. Nondemented LLD subjects age 65-85 y/o (n=50) who have completed a treatment study with a standard antidepressant will be recruited for imaging with PET and [11C]PIB, MRI, cognitive testing and ascertainment of clinical measures. Depressed subjects who did not respond to treatment (n=25) will be compared with responders (n=25) and with a non-demented non-depressed comparison sample (n=25). AIM 1: Compared with controls, LLD subjects will have elevated gray matter [11C]PIB binding. AIM 2: Compared with responders, a higher number of non-responders will have elevated gray matter [11C]PIB binding. AIM 3: Additional measures, including lifetime duration of depression, age of onset and comorbid vascular risk factors will be explored. Successful completion of this study will allow effect size and power calculations critical in designing a definitive study to determine whether LLD is associated with increased numbers of PIB + patients .