Vascular Cognitive and Motor Decline: Impact of aPL

血管认知和运动衰退：aPL 的影响

• 批准号: 8234526
• 负责人: Zoe Arvanitakis
• 金额: $ 64.85万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234526
• 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; Functional disorder; 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; Woman; aging population; cerebrovascular; clinical practice; cognitive function; cohort; disability; disorder control; follow-up; improved; inflammatory marker; men; mortality; motor impairment; nervous system disorder; neuroimaging; neuropathology; trend; vascular factor; white matter

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Cerebrovascular disease is increasing in prevalence with the aging population, and cognitive and motor decline, its' two most common consequences, are both major contributors to poor health outcomes and mortality. Identification of associated factors is priority for researchers in aging. These study relating blood vascular factors to cognitive and motor decline, and cerebrovascular disease, will fill a gap in knowledge in the field and has potential to provide data which will improve public health. an important

描述（由申请人提供）：脑血管疾病是衰老的最常见神经系统疾病之一，并且随着人口趋势的变化而越来越多。脑血管疾病的两个最常见的后果是认知和运动下降，这是造成健康结果和死亡率不佳的主要原因。确定相关因素，尤其是可获得治疗的因素，是研究人员衰老的优先事项。最近的数据表明，衰老的抗磷脂抗体（APL）增加，大约有80岁以上的人中约有35％。尽管APL增加了大约两倍的中风风险，但它们与认知和运动功能下降的关系可能是通过与临床和亚临床脑血管疾病的关联而尚不清楚。拟议的流行病学研究将利用1,100个社区居住的男女队列，这些男性和男性的随访率很高，并以高尸检率（R01AG17917）进行尸检，以测试APL与APL相关的假设与认知和运动的下降有关。该研究还将检查APL与脑血管疾病的关系，包括通过互补的前验尸神经成像和验尸神经病理学评估的亚临床脑血管疾病，以及在控制这种疾病后与APL与认知和运动障碍有关的程度。这表明除了将APL，认知和运动功能障碍联系起来的脑血管疾病以外，神经生物学机制的存在。最后，由于除血管以外的其他因素可能会影响关系，因此该研究将检查炎症制造者和血脑屏障渗透性改变的作用。拟议的研究将APL和其他标记与认知和运动的下降有关，以及在较老的社区居民中的脑血管疾病，将提供有关APL在常见的衰老常见神经系统状况中的作用的新知识。由于APL是可用治疗的常见血管因素，因此本研究将提供新的数据，从而通过转移当前的临床实践范式并减轻衰老中神经系统疾病的负担来改善公共卫生。 公共卫生相关性：脑血管疾病的患病率与人口老龄化，认知和运动下降（其两种最常见的后果）都是造成健康状况不佳和死亡率的主要原因。鉴定相关因素是研究人员衰老的优先级。这些研究将血管因素与认知和运动下降以及脑血管疾病有关，将填补该领域知识的空白，并具有提供可以改善公共卫生的数据。一个重要的