EFFCTS OF PIOGLITAZONE ON CGNTV FNCTION IN PTS W/MTBLC SYNDRM&MILD CGNTV IMPRMNT

吡格列酮对 MTBLC 综合征 PTS 患者 CGNTV 功能的影响

• 批准号: 7719533
• 负责人: PATRICIA HEYN
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719533
• 关键词: 2,4-thiazolidinedione; Age; Amyloid; Area; Biological Markers; Blood Vessels; Brain; Caregivers; Central obesity; Cognition; Cognitive; Collection; Computer Retrieval of Information on Scientific Projects Database; Computers; Data; Development; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Elderly; Exercise; Funding; Glucose Transporter; Grant; Health Care Costs; Healthcare Systems; Impaired cognition; Incidence; Inflammation; Inflammatory; Institution; Insulin; Insulin Receptor; Insulin Resistance; Intervention; Link; Localized; Measures; Memory; Memory impairment; Metabolic; Metabolic syndrome; Neurons; Neuropsychological Tests; Patients; Pilot Projects; Pioglitazone; Placebo Control; Plasma; Population; Prevalence; Production; Protocols documentation; Public Health; Quality of life; Randomized; Recruitment Activity; Research; Research Personnel; Resources; Score; Societies; Source; Staging; Testing; Thiazolidinediones; United States National Institutes of Health; Work; cognitive function; functional disability; glucose transport; improved; mild neurocognitive impairment; older patient; prevent; response; theories

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. Alzheimer¿??s Disease (AD) is a devastating disorder with impressive effects on patients, caregivers, the healthcare system and society as a whole. The incidence of AD increases with age and as the population ages, the prevalence will grow rapidly. New data suggests that there is a distinguishable prodromal state of AD, called mild cognitive impairment (MCI). MCI is defined as subjective and objective memory impairment without functional impairment. While all patients with AD go through a stage of MCI, not all MCI patients progress to AD. However, progression from MCI to AD is estimated to be ~15% per year. Metabolic Syndrome (MS) is a collection of inter-related metabolic abnormalities with the cardinal feature being insulin resistance (IR). Because of its strong relation to inactivity and central obesity, the prevalence of MS is growing rapidly and it is estimated to occur in ~50% of older adults. Recently, several large studies have linked MS to the development of cognitive impairment. Plausible theories to support this relationship include: 1) localized distribution of insulin receptors and neuronal production of insulin and glucose transport proteins in brain areas related to memory; 2) IR-related changes in insulin transport into the CNS; 3) effects of insulin on the amyloid cascade in the CNS; and 4) the pro-inflammatory state associated with MS. This pilot study proposes to investigate whether intervention to treat MS in older patients with co-existing MCI can improve, stabilize or lessen the decline in cognitive function compared to controls. The planned intervention, Pioglitazone (Pio), which is a thiazolidinedione (TZD),has been shown to improve MS, including IR, and also has been demonstrated to have positive effects on cognition. TZDs may work by: improving IR and enhancing glucose transporter-related glucose transport in specific brain areas; improving vascular reactivity; or reducing inflammation. We propose a double-blinded, placebo-controlled, randomized pilot study to investigate (compared to controls) the effect of Pio treatment on: a) cognitive function in older adults with co-existing MCI and MS; b) possible mechanisms of these effects on cognition (improved IR); c) associations between plasma levels of Amyloid¿??¿? and inflammatory biomarkers, and their possible relationships to improvements in IR and cognition. Fifty patients will be recruited and followed for 6-months of treatment. Cognitive funtion (CF) will be assessed by standardized computer testing and focused neuropsychologic testing; changes in IR will be measured by the HOMA score. The findings from this study will support Dr. Heyn¿??s Junior Investigator carreer towards the development of a full-scale NIH R01 study that will include: (1) variable doses of pioglitazone tailored to the IR response, (2) addition of exercise to the intervention protocol, which is known to be beneficial for both cognitive function and IR, and (3) inclusion of patients with diabetes. An intervention that can delay or prevent cognitive decline will be of great public health significance through decreasing the high health care costs related to Alzheimer¿??s disease and in improving the quality of life of elderly patients.

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。 老年痴呆症？阿尔茨海默病（AD）是一种毁灭性的疾病，对患者、护理人员、医疗保健系统和整个社会都有着令人印象深刻的影响。AD的发病率随着年龄的增长而增加，随着人口老龄化，患病率将迅速增长。新的数据表明，AD有一种可区分的前驱状态，称为轻度认知障碍（MCI）。MCI定义为不伴有功能损害的主观和客观记忆损害。虽然所有AD患者都经历MCI阶段，但并非所有MCI患者都进展为AD。然而，从MCI到AD的进展估计为每年约15%。代谢综合征（MS）是一组相互关联的代谢异常，其主要特征是胰岛素抵抗（IR）。由于其与不活动和向心性肥胖密切相关，MS的患病率正在迅速增长，估计约50%的老年人发生MS。最近，几项大型研究将MS与认知障碍的发展联系起来。支持这一关系的合理理论包括：1）胰岛素受体的局部分布和与记忆相关的脑区中胰岛素和葡萄糖转运蛋白的神经元产生; 2）IR相关的胰岛素转运到CNS的变化; 3）胰岛素对CNS中淀粉样蛋白级联的影响;和4）与MS相关的促炎状态。该初步研究提出调查在患有共存MCI的老年患者中治疗MS的干预是否可以改善，与对照组相比，稳定或减轻认知功能下降。计划的干预，吡格列酮（Pio），这是一种噻唑烷二酮（TZD），已被证明可以改善MS，包括IR，也已被证明对认知有积极的影响。TZD可以通过以下方式工作：改善IR和增强特定脑区域中葡萄糖转运蛋白相关的葡萄糖转运;改善血管反应性;或减轻炎症。 我们提出了一项双盲、安慰剂对照、随机化的初步研究，以调查（与对照组相比）Pio治疗对以下方面的影响：a）MCI和MS并存的老年人的认知功能; B）这些影响对认知（改善IR）的可能机制; c）血浆淀粉样蛋白水平之间的关联？和炎症生物标志物，以及它们与IR和认知改善的可能关系。将招募50名患者，并随访6个月的治疗。 认知功能（CF）将通过标准化计算机测试和集中的神经心理学测试进行评估; IR的变化将通过HOMA评分进行测量。这项研究的结果将支持Heyn博士？？的初级研究者进行了一项全面的NIH R 01研究，该研究将包括：（1）根据IR反应量身定制的吡格列酮的可变剂量，（2）在干预方案中增加运动，已知其对认知功能和IR均有益，以及（3）纳入糖尿病患者。一种可以延缓或预防认知能力下降的干预措施，通过降低与阿尔茨海默病相关的高昂医疗费用，将具有重大的公共卫生意义。对改善老年患者的生活质量具有重要意义。