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疾病中第六大致残原因。许多研究表明，混合年龄的BD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BD的老年人患痴呆症的风险可能会增加。一些研究人员认为BD是一种神经退行性过程。虽然有越来越多的证据表明，在混合年龄的成人BD患者中，局部脑萎缩和中枢神经系统（CNS）细胞丢失（神经元和神经胶质细胞），但尚不清楚这些变化是否是疾病生物学本身的产物，而不是与其他合并症（例如，血管疾病）的相互作用。很可能BD患者的脑组织容易受到衰老和“毒性”损伤的影响，这些损伤在老年表现为认知功能障碍。修订后的新研究者R 01（MH 084921）重点关注影响老年BD患者认知功能的因素。本研究的目的是确定老年BD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。作为本研究的一部分，我们将检查锂和丙戊酸盐的潜在神经保护和/或神经营养作用，这些作用可能会缓解认知功能障碍和认知能力下降的表达。在拟议研究的五年中，将收集100名50岁及以上BD I或II受试者和50名年龄、教育和医疗负担匹配的精神健康对照者的纵向临床、神经心理学、生物学和MRI数据。所有受试者将每年随访一次，持续3年，并将在基线和Y 03随访时进行脑部MRI。将在多个领域（信息处理速度、执行功能、语言、视觉空间能力、记忆和注意力）评估认知功能，并随时间进行跟踪。将检查与BD相关的特定因素（疾病持续时间、情绪发作的次数/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BD、血管疾病和其他病理因素与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，该大学在双相情感障碍和晚年情绪障碍方面有着良好的研究记录。 公共卫生相关性：双相情感障碍影响着大约600万美国成年人（约占美国18岁及以上人口的3%）。这项研究的重点是确定可能与双相情感障碍老年人认知能力加速下降有关的因素，以及阻止或逆转这些认知变化的潜在治疗方法。从这项研究中获得的知识不仅可以使双相情感障碍患者受益，还可以使更广泛的老年人群体受益，这些老年人患有与神经变性和过早认知下降相关的疾病。

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. PUBLIC HEALTH RELEVANCE: Bipolar Disorder affects approximately 6 million American adults (or about 3 percent of the U.S. population age 18 and older). This study focuses on identifying factors that may be related to accelerated cognitive decline in older adults with Bipolar Disorder and potential treatments that will stop or reverse these cognitive changes. The knowledge gained from this research may benefit not only patients with Bipolar Disorder, but the broader population of older adults at high risk for disorders associated with neurodegeneration and premature cognitive decline.