Vascular Risk Factors and Dementia in the Oldest-Old

描述（由申请人提供）：许多研究报告称，中年期间的血管风险因素（包括高血压和高胆固醇）会增加老年痴呆症的风险。这对痴呆症的预防具有重要意义，因为许多血管因素是可以改变的。然而，大多数研究都没有在最年长的老年人（90岁及以上的人）中探索这些关联，并且尚不清楚在晚年存在的相同血管风险因素是否与痴呆及其相关病理的风险增加有关。在对最年长参与者的初步研究中，我们发现高血压和高胆固醇史在患痴呆症的人中比没有患痴呆症的人更不常见。由于在年轻时，高血压和高胆固醇与痴呆风险增加有关，这些血管因素与痴呆之间的关系似乎随着年龄的变化而变化。因此，血管疾病的治疗建议可能是不同的非常老年人为年轻人。我们建议研究血管危险因素（即高血压和高胆固醇血症）和老年痴呆症风险之间的关系。第二个目标是在现有的大脑中产生新的微血管病变的措施，并调查血管危险因素和痴呆症之间的任何关联是否是由血管病变介导的。高血压将以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，通过参与者90岁及以上时的病史，以及通过90岁及以上时的直接血压测量。高胆固醇血症将通过病史和90岁及以上时获得的直接血脂测量结果进行类似定义。在相关性分析中将考虑血压和降脂药物的摄入。由于该提案是对二级数据分析公告的回应，因此大部分待分析的数据已经作为90+研究的一部分收集，该研究是最大的基于人口的90岁及以上人群的衰老和痴呆研究之一，他们在生活中进行了广泛的评估，其中一部分人同意在死亡后进行脑尸检。血管疾病和痴呆症都是最老的老年人非常常见的疾病。由于高龄老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公共卫生流行病。关键是要阐明潜在的可改变的因素和老年痴呆症在这个年龄组之间的关联。如果血管危险因素与痴呆症之间的关联随着年龄的变化而变化，那么治疗血管危险因素的风险和益处也可能随着年龄的变化而变化。由于目前大部分的健康实践依赖于管理血管疾病，发现老年人的血压降低和胆固醇降低对认知健康及其相关的病理无益，甚至可能有害，因此需要重新评估老年人的疾病管理实践。 公共卫生相关性：血管疾病和痴呆症都是高龄老人非常常见的疾病。由于最年长的老年人是人口中增长最快的部分， 在美国和许多其他国家，痴呆症有可能在未来几十年成为公共卫生流行病。因此，关键是要阐明潜在的可改变的因素和痴呆症在这个年龄组之间的关联。由于目前大部分的健康实践依赖于管理血管疾病，发现老年人的血压降低和胆固醇降低对认知健康及其相关的病理无益，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. 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.