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

双相情感障碍及其合并症对老年人认知的影响

• 批准号: 8207196
• 负责人: Ariel Gerard Gildengers
• 金额: $ 39.23万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8207196
• 关键词: Adult; Affect; Age; Alcohol or Other Drugs use; Alzheimer' s Disease; American; Amygdaloid structure; Atrophic; Attention; Biological; Biology; Bipolar Disorder; Brain; Cells; Clinical; Cognition; Cognitive; Cognitive deficits; Comorbidity; Data; Dementia; Developed Countries; Diffusion Magnetic Resonance Imaging; Disease; Elderly; Exposure to; General Population; Hippocampus (Brain); Impaired cognition; Investigation; Knowledge; Language; Lead; Linear Regressions; Lithium; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Medical; Medical Education; Memory; Methods; Modeling; Mood Disorders; Moods; Nerve Degeneration; Neuraxis; Neuroglia; Neurons; Pathologic; Patients; Pharmaceutical Preparations; Population; Prefrontal Cortex; Process; Property; Research; Research Personnel; Resolution; Risk; Severities; Signal Transduction; Stabilizing Agents; Statistical Methods; Structure; Symptoms; Temporal Lobe; Testing; Time; Universities; Vascular Diseases; Visuospatial; age effect; aged; base; brain tissue; cerebral atrophy; cognitive change; cognitive function; disability; executive function; follow-up; high risk; information processing; neuropsychological; normal aging; premature; processing speed; public health relevance; valproate; white matter

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.

描述（由申请人提供）：躁郁症（BD）是发达国家所有医疗疾病中残疾的第六个主要原因。许多研究表明，BD的混合年龄患者的认知缺陷在解决情绪症状后持续存在。此外，与普通人群相比，患有BD的长者可能会增加痴呆症的风险。一些研究人员认为，BD是一个神经退行性过程。尽管有越来越多的证据表明在混合老化的BD成年人中，有区域性脑萎缩和中枢神经系统（CNS）细胞损失（神经元和神经胶质），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的相互作用（例如，血管疾病）。 BD患者的脑组织很容易受到衰老和“有毒”侮辱的影响，这些侮辱在老年时表现为认知功能障碍。该修订后的新研究者R01（MH084921）的重点是理解影响BD老年人认知功能的因素。这项研究的目的是确定BD老年人的认知功能障碍在多大程度上是该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的相互作用，例如阿尔茨海默氏病。作为这项研究的一部分，我们将检查锂和丙戊酸的潜在神经保护作用和/或神经营养作用，这些作用可能调节认知功能障碍和下降的表达。在拟议的研究五年中，将在50岁及以上的BD I或II和50个心理健康的对照组中收集纵向临床，神经心理学，生物学和MRI数据，并在年龄，教育和医疗负担中匹配50个精神健康的对照。所有受试者将每年遵循3年，并在基线和Y03随访时进行大脑MRI。认知功能将在多个领域（信息处理速度，执行功能，语言，视觉空间能力，记忆和注意力）进行评估，并随着时间的流逝而进行跟踪。将检查与BD相关的特定因素（疾病的持续时间，情绪发作的数量/严重程度，医疗负担，药物使用和药物暴露），以识别基线认知功能的相关性，后续过程的预测因素以及BD，血管疾病，血管疾病以及其他病理学因素和大脑整合性的相关性。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用于基线分析的线性回归方法和纵向的广义混合效应模型。这项研究将在匹兹堡大学进行，该大学在进行双相情感障碍和晚期情绪障碍研究方面有很强的记录。 公共卫生相关性：躁郁症影响约600万美国成年人（约占18岁及以上的美国人口）。这项研究的重点是识别可能与双相情感障碍和潜在治疗的老年人加速认知下降有关的因素，这些因素将阻止或扭转这些认知变化。从这项研究中获得的知识不仅可能使躁郁症患者受益，而且使与神经退行性相关的疾病风险高的老年人人口更广泛。