Cardiovascular RF and Successful Cognitive Aging in Very Old Male Veterans

描述（由申请人提供）： 背景：认知能力下降是老年人的主要威胁，随着预期寿命的增加，这种情况可能会加速。大量证据表明，心血管风险因素（CVRF）也与认知能力下降的风险增加有关。然而，这一证据主要来自75岁以下的样本。我们小组和其他人的研究结果表明，高水平的CVRF与认知结果差之间的关系可能会在较老的样本中减弱或逆转。因此，这些风险因素可能是有用的指标，成功的认知老化-保持完整的认知到老年，尽管认知能力下降的风险很高。例如，在横断面分析中，我们的研究小组发现了C-反应蛋白（CRP）水平较高的挑衅性关联-这是与年轻老年人认知能力下降相关的炎症标志物-在非常老（75岁以上）的受试者中，记忆力更好，而不是更差，而且他们的家庭成员患痴呆症的风险更低。APOE基因的e4等位基因确实与认知能力下降和AD的风险增加相关，但这种相关性随着年龄的增长而减弱。APOE-e4与年龄的这种相互作用也可以解释为，对于没有APOE-e4等位基因的人来说，年龄与认知能力下降有更强的相关性。在其他几种CVRF（总胆固醇、血红蛋白A1 c、收缩压和射血分数，心脏功能的直接指标）中也观察到了与年龄的类似刺激性相互作用。研究方法：我们将研究从詹姆斯·J·彼得斯退伍军人事务医疗中心招募的非常老的、认知完整的、居住在社区的男性退伍军人。一些受试者已经签署知情同意书，在基线时进行了CVRF和认知评估，并进行了至少一次认知随访。我们将继续跟踪这些受试者的认知，并通过招募额外的非常老的第1组分数退伍军人来补充他们。我们将重点关注5个基线CVRF作为纵向认知变化的预测因子。目的：目的1评估总胆固醇、CRP、血红蛋白A1 c、射血分数、收缩压作为纵向认知能力下降率的预测因子。我们假设，CVRF的高风险基线水平与记忆功能下降率较低相关。目标2比较了入组时年龄超过85岁（最年长）的受试者与年龄在75-84岁之间（中等年龄）的受试者的这些关联。我们假设，与年轻老年人心血管风险较高相关的基线CVRF水平，与中老年人相比，与老年人记忆功能下降率较低相关。目的3通过载脂蛋白E4等位基因的存在或不存在来比较这些关联。我们假设，基线CVRF水平与更大的心血管疾病的风险，在年轻的老年人将与较低的利率下降的记忆功能的受试者没有一个APOE-e4等位基因比那些与it. Public健康的影响：由于有很少的研究集中在非常老的男性，这项研究将有重大的公共卫生影响的老年退伍军人，和一般人群。识别与CVRF相关的特别高风险的亚组有可能针对性地预防或治疗认知能力下降。本研究的创新之处在于寻找老年男性退伍军人认知成功的预测因素，这些退伍军人是高风险的损伤，这可能导致识别保护或预防因素。

DESCRIPTION (provided by applicant): Background: Cognitive decline is a major threat to the elderly, which can be expected to accelerate as life expectancy increases. Extensive evidence indicates cardiovascular risk factors (CVRFs) are also associated with an increased risk of cognitive decline. This evidence, however, comes from samples predominantly under age 75. Findings from our group and others suggest that relationships between high levels of CVRFs with poor cognitive outcomes may be diminished or reversed in older samples. Thus, such risk factors might be useful as indicators for successful cognitive aging - maintaining intact cognition into old age despite a high risk of cognitive decline. For example, in cross-sectional analyses, our group has found provocative associations of greater levels of the C-reactive protein (CRP) - a marker for inflammation associated with cognitive decline in the younger elderly - with better, not worse, memory in very old (75+ years) subjects, and also with lower risk for dementia in their family members. The e4 allele of the APOE gene is conclusively associated with increased risk for cognitive decline and AD, but this association diminishes with increasing age. This interaction of APOE-e4 and age may also be interpreted as a stronger association of age with cognitive decline for those without the APOE-e4 allele. Similar provocative interactions with age have been observed with several other CVRFs - total cholesterol, hemoglobin A1c, systolic blood pressure, and ejection fraction, a direct measure of heart function. Methods: We will study very old, cognitively intact, community-dwelling, male Veterans recruited from the James J. Peters Veterans Affairs Medical Center. Some of the subjects have already been consented, assessed for CVRFs and cognition at baseline, and followed cognitively at least once. We will continue to follow these subjects cognitively, and supplement them by recruiting additional very old Group 1 scores Veterans. We will focus on five baseline CVRFs as predictors of longitudinal cognitive change. Objectives: Aim 1 assesses total cholesterol, CRP, hemoglobin A1c, ejection fraction, systolic blood pressure as predictors of the rate of longitudinal cognitive decline. We hypothesize that putatively high risk baseline levels of CVRFs will be associated with a lower rate of decline of memory function. Aim 2 compares these associations for subjects over age 85 at entry (oldest-old) with those between age 75-84 (moderately-old). We hypothesize that baseline CVRF levels associated with greater cardiovascular risk in the young elderly will be associated with lower rates of decline of memory function in the oldest old than the moderately old. Aim 3 compares these associations by the presence or absence of the apoliprotein E4 allele. We hypothesize that baseline CVRF levels associated with greater cardiovascular risk in the young elderly will be associated with lower rates of decline of memory function in subjects without an APOE-e4 allele than in those with it. Public Health Implications: Since there are few studies focusing on very old males, this study will have major public health implications for elderly veterans, and the general population. Identifying subgroups with particularly high risk associated with CVRFs has the potential for targeting preventions against or treatments of cognitive decline. The innovation of this study is seeking predictors of cognitive success in very old male veterans who are high risk for impairment, which may lead to identification of protective or preventive factors.