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.

项目摘要： 脑血管疾病是衰老的最常见神经系统疾病之一，正在增加 随着人口趋势的变化而患病率。脑血管的两个最常见的后果 疾病是认知和运动下降的，这是造成健康状况不佳和死亡率的主要贡献者。 确定相关因素，尤其是可用治疗的因素，是研究人员的优先事项 在衰老中。最近的数据表明，抗磷脂抗体（APL）的衰老增加，并且存在于 80岁以上的人中约有35％。而APL将中风的风险增加了大约两倍，但 与认知和运动功能下降有关，也许是通过与临床和 亚临床脑血管疾病尚不清楚。拟议的流行病学研究将利用 1,100名社区居民的队列以高度随访的速度跟踪， 谁以高尸检率进行尸检（R01AG17917），以测试APL相关的假设 认知和运动下降。该研究还将检查APL与脑血管疾病的关系， 包括通过互补前验尸神经影像和 验尸神经病理学，以及APL与认知和运动障碍有关的程度 控制这种疾病。这表明除了神经生物学机制以外的存在 将APL和认知和运动功能障碍联系起来的脑血管疾病。最后，因为有影响的因素 除血管外可能影响关系外，该研究将研究炎症制造者的作用和 血脑屏障的渗透性改变。拟议的研究，将APL和其他标记与认知和其他标记有关 较老的社区居民的运动衰落和脑血管疾病将提供新知识 关于APL在衰老的常见神经系统状况中的作用。因为APL是常见的血管 可用治疗的因素，本研究将提供新数据，有可能改善 通过转移当前的临床实践范例并减轻神经系统疾病的负担来公共卫生 老化。