Vascular Cognitive and Motor Decline: Impact of aPL

描述（由申请人提供）：脑血管疾病是老年人最常见的神经系统疾病之一，随着人口统计学趋势的变化，其患病率正在增加。脑血管疾病的两个最常见的后果是认知和运动能力下降，这是导致不良健康结局和死亡率的主要因素。确定相关因素，特别是那些治疗方法，是研究人员在老龄化的优先事项。最近的数据表明，抗磷脂抗体（aPL）的增加，在老化，并存在于约35%的人超过80岁。虽然aPL使中风风险增加约两倍，但其与认知和运动功能下降的关系（可能通过与临床和亚临床脑血管疾病的相关性）尚不清楚。拟议的流行病学研究将利用一个由1，100名社区居住的女性和男性组成的队列，这些女性和男性接受了高随访率的纵向随访，并以高尸检率进行尸检（R01AG 17917），以检验aPL与认知和运动功能下降相关的假设。该研究还将研究aPL与脑血管疾病的关系，包括通过补充性生前神经成像和死后神经病理学评估的亚临床脑血管疾病，以及控制这种疾病后aPL与认知和运动障碍的相关程度。这表明存在脑血管疾病以外的神经生物学机制，将aPL与认知和运动功能障碍联系起来。最后，由于血管以外的其他因素可能会影响关系，该研究将检查炎症和改变血脑屏障通透性的制造商的作用。拟议中的研究，aPL和其他标志物的认知和运动能力下降，脑血管疾病的老年人，社区居民，将提供新的知识的作用，aPL在常见的神经系统疾病的老化。由于aPL是常见的血管因素，治疗是可用的，这项研究将提供新的数据，有可能通过改变目前的临床实践模式和减少衰老中神经系统疾病的负担来改善公共健康。 公共卫生相关性：随着人口老龄化，脑血管疾病的患病率正在增加，认知和运动能力下降是其两个最常见的后果，也是导致健康状况不佳和死亡的主要原因。识别相关因素是老龄化研究者的首要任务。这些研究将血管因素与认知和运动能力下降以及脑血管疾病联系起来，将填补该领域的知识空白，并有可能提供改善公众健康的数据。一个重要

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