The Effects of Bipolar Disorder and its Comorbidities on Cognition in Older Adult

描述（由申请人提供）：双相情感障碍（BD）是发达国家所有医学障碍中第六大致残原因。许多研究表明，混龄双相障碍患者在情绪症状消退后仍存在认知缺陷。此外，与一般人群相比，患有双相障碍的老年人患痴呆症的风险可能更高。一些研究者认为双相障碍是一种神经退行性过程。尽管有越来越多的证据表明，混合性双相障碍老年患者存在区域性脑萎缩和中枢神经系统（CNS）细胞（包括神经元和神经胶质细胞）损失，但尚不清楚这些变化是疾病生物学本身的产物，还是与其他合共病（例如血管疾病）的相互作用。这可能是因为双相障碍患者的脑组织容易受到衰老和“有毒”损伤的影响，这些损伤在老年时表现为认知功能障碍。这项修订后的新研究者R01 （MH084921）的重点是了解影响老年双相障碍患者认知功能的因素。这项研究的目的是确定老年双相障碍患者的认知功能障碍在多大程度上是疾病生物学本身的产物，而不是与血管疾病和其他病理因素（如阿尔茨海默病）的相互作用。作为这项研究的一部分，我们将研究锂和丙戊酸盐的潜在神经保护和/或神经营养作用，这些作用可能会减缓认知功能障碍和衰退的表达。在5年的研究中，将收集100名50岁及以上BD I或II患者的纵向临床、神经心理学、生物学和MRI数据，以及50名年龄、教育程度和医疗负担相匹配的心理健康对照。所有受试者将每年随访3年，并在基线和Y03随访时进行脑MRI检查。认知功能将跨越多个领域（信息处理速度、执行功能、语言、视觉空间能力、记忆和注意力）进行评估，并随着时间的推移进行跟踪。将检查与双相障碍相关的特定因素（疾病持续时间、情绪发作次数/严重程度、医疗负担、物质使用和药物暴露），以确定基线认知功能的相关性、后续病程的预测因素，以及双相障碍、血管疾病和其他病理因素与大脑完整性之间的关系。此外，我们将研究这些因素如何与大脑结构相互作用以预测认知功能。假设检验的统计方法将包括基线分析的线性回归方法和纵向分析的广义混合效应模型。这项研究将在匹兹堡大学进行，该大学在开展双相情感障碍和晚年情绪障碍的研究方面有着良好的记录。

DESCRIPTION (provided by applicant): Bipolar disorder (BD) is the sixth leading cause of disability among all medical disorders in developed countries. Many studies have shown that mixed-aged patients with BD have cognitive deficits that persist after the resolution of mood symptoms. Further, elders with BD may be at increased risk for dementia compared to the general population. Some investigators have argued that BD is a neurodegenerative process. Although there is mounting evidence that shows regional brain atrophy and central nervous system (CNS) cell loss (both neurons and glia) in mixed aged adults with BD, it is not yet clear whether these changes are the product of the disease biology itself, versus an interaction with other comorbidities (for example, vascular disease). It is likely that the brain tissue of patients with BD is vulnerable to the effects of aging and "toxic" insults that manifest themselves in older age as cognitive dysfunction. This revised New Investigator R01 (MH084921) is focused on understanding the factors influencing cognitive function in older adults with BD. The aim of this study is to determine to what extent cognitive dysfunction in older adults with BD is a product of the disease biology itself, versus an interaction with vascular disease and other pathologic factors, such as Alzheimer's disease. As part of this investigation, we will examine the potential neuroprotective and/or neurotrophic effects of lithium and valproate that may moderate the expression of cognitive dysfunction and decline. Over the five years of the proposed study, longitudinal clinical, neuropsychological, biological, and MRI data will be collected in 100 subjects 50 years and older with BD I or II and 50 mentally healthy controls matched on age, education, and medical burden. All subjects will be followed annually for 3 years and will have brain MRI at baseline and Y03 follow-up. Cognitive function will be assessed across multiple domains (information processing speed, executive function, language, visuospatial ability, memory, and attention) and tracked over time. Specific factors associated with BD will be examined (duration of illness, number/severity of mood episodes, medical burden, substance use, and medication exposure) to identify correlates of baseline cognitive function, predictors of subsequent course, and the relationship between BD, vascular disease, and other pathologic factors and brain integrity. Further, we will examine how these factors interact with brain structure to predict cognitive function. Statistical methods for hypothesis testing will include linear regression methods for baseline analyses and generalized mixed-effects models for longitudinal. This study will be conducted at the University of Pittsburgh, which has a strong record of conducting research in bipolar disorder and late-life mood disorders.