Vascular Cognitive and Motor Decline: Impact of aPL

描述(申请人提供)：脑血管疾病是最常见的老年神经系统疾病之一，随着人口趋势的变化，其患病率正在增加。脑血管疾病最常见的两个后果是认知和运动能力下降，这是造成不良健康结果和死亡率的主要原因。确定相关因素，特别是那些可以治疗的因素，是研究人员在老龄化问题上的优先事项。最近的数据表明，抗磷脂抗体(APL)随着年龄的增长而增加，约35%的80岁以上的人存在抗磷脂抗体。虽然APL使中风的风险增加了大约两倍，但它们与认知和运动功能下降的关系尚不清楚，这可能是通过与临床和亚临床脑血管疾病的关联来实现的。拟议的流行病学研究将利用1100名居住在社区的女性和男性的队列，他们被纵向跟踪，随访率高，尸检比率高(R01AG17917)，以检验APL与认知和运动能力下降有关的假设。这项研究还将探讨APL与脑血管疾病的关系，包括通过死前补充神经成像和死后神经病理学评估的亚临床脑血管疾病，以及在控制这种疾病后APL与认知和运动障碍的关系程度。这可能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，这项研究将检查炎症标志物和血脑屏障通透性改变的作用。这项拟议的研究将APL和其他标记物与老年人的认知和运动能力下降以及脑血管疾病联系起来，将提供关于APL在常见神经衰老疾病中的作用的新知识。由于APL是常见的可治疗的血管因素，这项研究将提供新的数据，有可能通过改变当前的临床实践范式和减轻老龄化中神经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上升，其最常见的两个后果--认知和运动能力下降--都是导致健康状况不佳和死亡率下降的主要原因。相关因素的识别是老龄化研究人员的首要任务。这些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的研究，将填补该领域知识的空白，并有可能提供改善公众健康的数据。一个重要的

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