Vascular Risk Factors and Dementia in the Oldest-Old

描述(申请人提供)：许多研究报告称，中年期间的血管危险因素(包括高血压和高胆固醇)会增加晚年患痴呆症的风险。这对预防痴呆症具有重要意义，因为许多血管因素是可以改变的。然而，大多数研究没有探索高龄老人(90岁及以上的人)的这些联系，也不清楚同样的血管风险因素在晚年是否与痴呆症及其相关病理的风险增加有关。在对年龄最大的参与者的初步研究中，我们发现患有痴呆症的人比没有患痴呆症的人更少有高血压和高胆固醇史。由于在较年轻的年龄，高血压和高胆固醇与痴呆症风险增加有关，这些血管因素和痴呆症之间的关系似乎随着年龄的变化而变化。因此，对老年人和年轻人的血管疾病治疗建议可能是不同的。我们建议研究血管危险因素(即高血压和高胆固醇血症)与老年痴呆风险之间的关系。第二个目标是在现有的大脑中产生新的微血管病理指标，并调查血管风险因素和痴呆症之间的任何联系是否由血管病理介导。高血压将通过几种不同的方式进行评估；通过参与者平均70岁时收集的病史，根据参与者90岁及以上的病史，以及通过90岁及以上的直接血压测量。高胆固醇血症的定义类似于90岁及以上的病史和直接的血脂测量。血压和降脂药物的摄入将在相关性分析中考虑在内。由于这项提议是对二次数据分析公告的回应，大部分要分析的数据已经作为90研究的一部分收集起来，这是关于90岁及以上人群中老龄化和痴呆症的最大基于人群的研究之一，这些人在一生中接受了广泛的评估，其中一部分人已经同意在死亡时接受脑部尸检。血管疾病和痴呆症在最年长的老年人中都是非常常见的疾病。由于老年人是美国人口中增长最快的部分，痴呆症将在未来几十年成为一种公共卫生流行病。在这个年龄段，阐明潜在的可改变因素与痴呆之间的联系是至关重要的。如果血管危险因素和痴呆症之间的关联随着年龄的变化而改变，那么治疗血管危险因素的风险和好处也可能随着年龄的变化而改变。由于目前的健康实践大多依赖于血管疾病的管理，发现高龄人群降低血压和降低胆固醇对认知健康及其相关病理无益，甚至可能是有害的，因此需要重新评估高龄人群的疾病管理实践。 公共卫生相关性：血管疾病和痴呆症在最年长的老年人中都是非常常见的疾病。因为最年长的老人是#年人口增长最快的部分 在美国和其他许多国家，痴呆症有可能在未来几十年成为一种公共卫生流行病。因此，阐明潜在的可改变因素与这个年龄段的痴呆之间的关联是至关重要的。由于目前的健康实践大多依赖于血管疾病的管理，发现高龄人群降低血压和降低胆固醇对认知健康及其相关病理无益，甚至可能是有害的，因此需要重新评估高龄人群的疾病管理实践。

DESCRIPTION (provided by applicant): Vascular risk factors (including hypertension and high cholesterol) during mid-life have been reported by many studies to increase the risk for dementia in later life. This has significant implications for dementia prevention as many vascular factors are modifiable. Most studies, however, have not explored these associations in the oldest-old (people 90 years and older) and it is not clear if the same vascular risk factors when present in very late-life are associated with increased risk of dementia and its related pathologies. In a preliminary study of oldest-old participants, we found a history of high blood pressure and history of high cholesterol to be less common in people who developed dementia compared to people who did not. Because at younger ages high blood pressure and high cholesterol are associated with increased dementia risk dementia, the relationship between these vascular factors and dementia appear to change with age. Thus, recommendations for treatment of vascular disease may be different for the very elderly as for younger people. We propose to study the association between vascular risk factors (namely hypertension and hypercholesterolemia) and risk of dementia in the oldest-old. A second objective is to generate new measures of microvascular pathologies in existing brains and investigate whether any association between vascular risk factors and dementia are mediated by vascular pathologies. Hypertension will be assessed in several different ways; by history collected when participants were on average 70 years of age, by history when participants were 90 years and older, and by direct blood pressure measurements at age 90 and older. Hypercholesterolemia will be similarly defined by history and direct lipid measurements obtained at age 90 and older. Intake of blood pressure and lipid lowering medications will be accounted for in the analyses of the associations. As this proposal is in response to an secondary data analysis announcement, most of the data to be analyzed has already been collected as part of The 90+ Study, one of the largest population-based studies of aging and dementia in people aged 90 years and older who have been extensively evaluated during life and a subset of them have agreed to undergo brain autopsy upon death. Vascular disease and dementia are both very common conditions in the oldest-old. As the oldest-old is the fastest growing segment of the population in the United States, dementia will become a public health epidemic in the coming decades. It is crucial to elucidate the association between potentially modifiable factors and dementia in this age group. If the associations between vascular risk factors and dementia change with age, the risks and benefits of treating vascular risk factors may also change with age. As much of current health practice relies on managing vascular disease, finding that reduced blood pressure and reduced cholesterol in the very elderly are not beneficial for cognitive health and its associated pathologies, and may even be harmful, disease management practices would need to be re-evaluated for the very elderly. PUBLIC HEALTH RELEVANCE: Vascular disease and dementia are both very common conditions in the oldest-old. As the oldest-old is the fastest growing segment of the population in the United States and many other countries, dementia threatens to become a public health epidemic in the coming decades. It is thus crucial to elucidate the association between potentially modifiable factors and dementia in this age group. As much of current health practice relies on managing vascular disease, finding that reduced blood pressure and reduced cholesterol in the very elderly are not beneficial for cognitive health and its associated pathologies, and may even be harmful, disease management practices would need to be re-evaluated for the very elderly.