Vascular Cognitive and Motor Decline: Impact of aPL

血管认知和运动衰退：aPL 的影响

• 批准号: 8881036
• 负责人: Zoe Arvanitakis
• 金额: $ 52.74万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8881036
• 关键词: Address; Aged, 80 and over; Aging; Antibodies; Antiphospholipid Antibodies; Autopsy; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood specimen; Brain; C-reactive protein; Cardiolipins; Cell physiology; Cerebrovascular Disorders; Cessation of life; Clinical; Cognition; Cognitive; Cohort Studies; Communities; Consensus; Data; Disease; Elderly; Epidemiologic Studies; Epidemiology; Glycoproteins; Goals; Health; High Prevalence; Impaired cognition; Impairment; Infarction; Inflammation; International; Ischemic Stroke; Knowledge; Link; Literature; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Mediating; Memory; Microscopic; Motor; Neurologic; Neurologic Dysfunctions; Neuropsychological Tests; Outcome; Pathologic; Pathway interactions; Performance; Permeability; Persons; Prevalence; Public Health; Research Personnel; Risk; Role; Serine; Stroke; Systemic Lupus Erythematosus; Testing; Time; White Matter Hyperintensity; Woman; aging population; cerebrovascular; clinical practice; cognitive function; cohort; disability; disorder control; follow-up; improved; inflammatory marker; men; mortality; motor disorder; motor impairment; nervous system disorder; neuroimaging; neuropathology; trend; vascular factor

PROJECT SUMMARY: Cerebrovascular disease is among the most common neurological diseases of aging and is increasing in prevalence with changing demographic trends. The two most common consequences of cerebrovascular disease are cognitive and motor decline, which are major contributors to poor health outcomes and mortality. Identifying associated factors, particularly ones for which treatments are available, is a priority for researchers in aging. Recent data suggest that antiphospholipid antibodies (aPL) increase in aging, and are present in about 35% of persons over the age of 80 years. While aPL increase risk of stroke by about two-fold, their relation to decline in cognitive and motor function, perhaps through an association with both clinical and subclinical cerebrovascular disease, is unclear. The proposed epidemiologic study will take advantage of a cohort of 1,100 community-dwelling women and men who are followed longitudinally with a high follow-up rate, and who come to autopsy with a high autopsy rate (R01AG17917), to test the hypotheses that aPL are related to cognitive and motor decline. The study will also examine the relation of aPL to cerebrovascular disease, including subclinical cerebrovascular disease assessed by complementary ante-mortem neuroimaging and postmortem neuropathology, and the extent to which aPL are related to cognitive and motor impairment after controlling for this disease. This would suggest the existence of neurobiologic mechanisms other than cerebrovascular disease linking aPL and cognitive and motor dysfunction. Finally, because factors with effects other than vascular may influence relations, the study will examine the role of makers of inflammation and altered blood-brain barrier permeability. The proposed study, relating aPL and other markers to cognitive and motor decline, and cerebrovascular disease in older, community-dwelling persons, will provide new knowledge regarding the role of aPL in common neurological conditions of aging. Because aPL are common vascular factors for which treatments are available, this study will provide new data which has the potential to improve public health by shifting current clinical practice paradigms and reducing the burden of neurological disease in aging.

项目概要： 脑血管疾病是最常见的神经系统疾病之一， 随着人口趋势的变化。脑血管病最常见的两种后果 这些疾病是认知和运动能力下降，这是造成健康状况不佳和死亡率的主要因素。 确定相关因素，特别是那些可用治疗的因素，是研究人员的首要任务 在衰老。最近的数据表明，抗磷脂抗体（aPL）的增加，在老化，并存在于 80岁以上的人约占35%。虽然aPL使中风风险增加约两倍， 与认知和运动功能下降有关，可能与临床和 亚临床脑血管病，尚不清楚。拟议的流行病学研究将利用一个 对1 100名社区男女进行了纵向随访，随访率很高， 和尸检率高的人（R01AG17917），以检验aPL相关的假设 认知和运动能力下降这项研究还将研究aPL与脑血管疾病的关系， 包括通过补充性生前神经成像评估的亚临床脑血管疾病， 死后神经病理学，以及aPL与死后认知和运动障碍相关的程度。 控制这种疾病。这可能表明存在神经生物学机制，而不是 脑血管疾病与aPL和认知及运动功能障碍有关。最后，因为影响因素 除了血管可能影响的关系，该研究将检查炎症制造者的作用， 改变血脑屏障通透性这项研究将aPL和其他标记物与认知和 运动能力下降和脑血管疾病的老年人，社区居民，将提供新的知识， 关于aPL在常见的衰老神经系统疾病中的作用。因为aPL是常见的血管 这些因素的治疗是可用的，这项研究将提供新的数据，有可能改善 通过改变当前的临床实践模式和减少神经疾病的负担， 衰老