Vascular Risk Factors and Dementia in the Oldest-Old

描述（由申请人提供）：许多研究报道了中年血管危险因素（包括高血压和高胆固醇）会增加晚年痴呆的风险。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，大多数研究并没有在老年人（90岁及以上的人）中探索这些关联，也不清楚同样的血管危险因素在非常晚年时是否与痴呆及其相关病理的风险增加有关。在一项针对最年长参与者的初步研究中，我们发现，与没有患痴呆症的人相比，患痴呆症的人有高血压和高胆固醇病史的情况更少。因为在年轻的时候，高血压和高胆固醇与痴呆症的风险增加有关，这些血管因素和痴呆症之间的关系似乎随着年龄的增长而改变。因此，对于老年人和年轻人的血管疾病治疗建议可能不同。我们建议研究血管危险因素（即高血压和高胆固醇血症）与老年人痴呆风险之间的关系。第二个目标是生成现有大脑微血管病变的新测量方法，并研究血管病变是否介导了血管危险因素与痴呆之间的任何关联。高血压将以几种不同的方式进行评估；通过参与者平均年龄为70岁时收集的历史，参与者90岁及以上时的历史，以及90岁及以上时直接测量的血压。高胆固醇血症同样可以通过90岁及以上的病史和直接脂质测量来定义。血压和降脂药物的摄入将在相关分析中考虑。由于这一提议是对二级数据分析公告的回应，大部分需要分析的数据已经作为90+研究的一部分收集，这是最大的基于90岁及以上人群的衰老和痴呆研究之一，这些人在生前得到了广泛的评估，其中一部分人已经同意在死亡时进行大脑解剖。血管疾病和痴呆都是老年人非常常见的疾病。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。阐明这一年龄组的潜在可改变因素与痴呆之间的关系至关重要。如果血管危险因素和痴呆之间的关联随着年龄的增长而变化，那么治疗血管危险因素的风险和益处也可能随着年龄的增长而变化。由于目前的许多健康实践依赖于管理血管疾病，发现老年人降低血压和降低胆固醇对认知健康及其相关病理没有好处，甚至可能有害，因此需要重新评估老年人的疾病管理实践。

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.