PET AMYLOID PLAQUE IMAGING IN LATE LIFE DEPRESSION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 晚年抑郁症（LLD）是一种常见的使人衰弱的问题，可能表明发生认知障碍的风险较高。 我们目前的基金“血管性抑郁症的治疗结果”MH 60697收集了大量LLD患者（n=120）和对照组（n=40）的样本，以前瞻性地检查白色疾病、脑血管危险因素和认知功能。 然而，LLD是一种异质性疾病，对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初期痴呆的表现症状。 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，是可能导致不良结局的重要因素，包括LLD的治疗抵抗。 一种用于体内脑淀粉样蛋白成像的新型药物，[11 C]PIB，提供了确定LLD受试者是否具有异常脑淀粉样蛋白结合的机会。 我们有初步数据显示LLD中PIB +状态增加3倍：3/10例LLD患者vs 2/20例对照为PIB +。另外2/5抗抑郁药无应答者（NR）vs 1/5应答者（R）PIB+。 在目前的提案中，我们使用[11 C]PIB的PET成像来收集初步数据，以调查与对照受试者相比，脑PIB结合是否与LLD相关，特别是在LLD治疗无应答者和长期抑郁症患者中。 如果这个PET数据支持我们的假设，我们将使用这个试点数据集作为更大的资助申请的基础，以进一步探索这些关系。 我们还从最初的“治疗结果”研究中获得了许多其他关键的神经影像学、认知和临床数据，并将探讨它们在多大程度上为LLD提供了显著的预测作用。 将招募已完成标准抗抑郁药治疗研究的65-85岁非痴呆LLD受试者（n=50）进行PET和[11 C]PIB成像、MRI、认知测试和临床测量确定。 将对治疗无应答的抑郁受试者（n = 25）与应答者（n=25）和非痴呆非抑郁对照样本（n=25）进行比较。 目的1：与对照组相比，LLD受试者的灰质[11 C]PIB结合水平升高。 目的2：与应答者相比，更多数量的无应答者将具有升高的灰质[11 C]PIB结合。 目的3：其他措施，包括抑郁症的终生持续时间，发病年龄和共病血管危险因素将进行探讨。 本研究的成功完成将使效应量和把握度计算在设计确定性研究以确定LLD是否与PIB +患者数量增加相关时至关重要。

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 .