PET Amyloid Plaque Imaging in Late Life Depression

PET 淀粉样斑块成像在晚年抑郁症中的应用

• 批准号: 7078207
• 负责人: YVETTE I SHELINE
• 金额: $ 17.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7078207
• 关键词: Alzheimer' s disease; amyloid proteins; antidepressants; behavioral /social science research tag; bioimaging /biomedical imaging; biomarker; cardiovascular disorder risk; clinical research; cognition disorders; comorbidity; gray matter; human old age (65+); human subject; magnetic resonance imaging; major depression; neuroimaging; neuropsychological tests; positron emission tomography; prognosis; protein binding; psychological aspect of aging; psychopharmacology; radiotracer; sertraline; Alzheimer' s disease; amyloid proteins; antidepressants; behavioral /social science research tag; bioimaging /biomedical imaging; biomarker; cardiovascular disorder risk; clinical research; cognition disorders; comorbidity; gray matter; human old age (65+); human subject; magnetic resonance imaging; major depression; neuroimaging; neuropsychological tests; positron emission tomography; prognosis; protein binding; psychological aspect of aging; psychopharmacology; radiotracer; sertraline

DESCRIPTION (provided by applicant): 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 heterogeneous 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 dementia. 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) were PIB+. In our current proposal, we use PET imaging of [11C] P1B 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 hypotheses, 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 (sertraline) 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). AIM1: Compared with controls, LLD subjects will have elevated gray matter [11C] PIB binding. AIM2: 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, untreated episodes 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.

描述（由申请人提供）：生命后期抑郁症（LLD）是一个常见且令人衰弱的问题，可能表明患有认知障碍的风险更高。我们目前的“血管抑郁症治疗结果” MH60697收集了大量的LLD患者和对照组（n = 40）的样本（n = 120），以检查白质疾病，脑血管危险因素和认知功能。但是，LLD是一种异质性疾病，开发的危险因素知之甚少。血管疾病和起步性痴呆都是常见的合并症综合征。实际上，LLD抑郁症状可能是起步痴呆的症状。另外，LLD可能是AD的独立危险因素。因此，可能是在DAT之前数年之前的初期痴呆症是可能导致不良预后的重要因素，包括LLD的治疗耐药性。 [11C] PIB在体内成像脑淀粉样蛋白的新型药物为确定患有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中的PIB+状态增加了3倍：3/10 LLD患者与2/20对照是PIB+。进一步的2/5抗抑郁药非反应器（NR）与1/5响应者（R）为PIB+。在当前的建议中，我们使用[11C] P1B的PET成像来收集初步数据，以调查与对照组受试者相比，脑PIB结合升高是否与LLD相关，尤其是在LLD治疗无反应者和长期抑郁症患者中。如果此PET数据显示对我们的假设的支持，我们将使用此试验数据集作为更大的赠款应用程序的基础，以进一步探索这些关系。我们还从我们的原始“治疗结果”研究中获得了许多其他关键的神经影像，认知和临床数据，并将探索它们为LLD提供重要的预测效应的程度。已完成使用标准抗抑郁药（舍曲林）的治疗研究的65-85 y/o（n = 50）的非训练的LLD受试者将被招募，用于使用PET和[11C] PIB，MRI，认知测试和确定临床测量的[11C] PIB，MRI，MRI，认知测试和确定。对治疗没有反应的抑郁受试者（n = 25）将与反应者（n = 25）和非痴呆的不抑制比较样本进行比较（n = 25）。 AIM1：与对照组相比，LLD受试者的灰质[11C] PIB结合将升高。 AIM2：与响应者相比，较高数量的非反应者将具有升高的灰质[11C] PIB结合。 AIM 3：将探讨其他措施，包括抑郁症的寿命持续时间，未处理的抑郁症发作，发病年龄和合并症血管危险因素。这项研究的成功完成将允许效应大小和功率计算在设计确定的研究中至关重要，以确定LLD是否与PIB+患者数量增加有关。