Cardiovascular RF and Successful Cognitive Aging in Very Old Male Veterans

描述(由申请人提供)： 背景：认知衰退是对老年人的一大威胁，可以预计随着预期寿命的增加，认知衰退会加速。广泛的证据表明，心血管危险因素(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，在较老的样本中，高水平的CVRF与认知结果差之间的关系可能会减弱或颠倒。因此，这些风险因素可能是成功认知老化的指标--尽管认知衰退的风险很高，但在老年时仍保持完整的认知。例如，在横断面分析中，我们的团队发现，C-反应蛋白(CRP)水平较高--一种与较年轻老年人认知能力下降相关的炎症标志--与高龄(75岁以上)受试者的记忆力更好而不是更差，以及他们的家庭成员患痴呆症的风险较低之间存在着挑衅性的关联。APOE基因的e4等位基因与认知功能减退和阿尔茨海默病的风险增加有决定性的关联，但这种关联随着年龄的增长而减弱。对于那些没有apoe-e4等位基因的人来说，apoE-e4和年龄的相互作用也可能被解释为年龄与认知能力下降的更强关联。与年龄类似的挑衅性相互作用也被观察到与其他几种CVRF-总胆固醇、血红蛋白A1c、收缩压和射血分数(心脏功能的直接测量)。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年长、认知完好、居住在社区的男性退伍军人。其中一些受试者已经获得同意，在基线时对CVRF和认知进行了评估，并至少进行了一次认知跟踪。我们将继续从认知上关注这些主题，并通过招募额外的非常老的第一组成绩退伍军人来补充这些主题。我们将重点关注五个基线的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、C反应蛋白、血红蛋白A1c、射血分数、收缩压作为纵向认知功能减退的预测因子。我们假设CVRF的高风险基线水平将与较低的记忆功能衰减率相关。目的2比较年龄在85岁以上的受试者(年龄最大的)和年龄在75-84岁之间的受试者(中老年)的这些关联。我们假设，与年轻老年人心血管风险较大相关的基线CVRF水平将与高龄老年人记忆功能减退率低于中老年人相关。目的3通过载脂蛋白E4等位基因的存在与否来比较这些关联。我们假设，在年轻的老年人中，与更大的心血管风险相关的基线CVRF水平将与没有APOE-e4等位基因的受试者比有APOE-e4等位基因的受试者记忆功能减退率更低相关。公共卫生影响：由于很少有研究关注高龄男性，这项研究将对老年退伍军人和普通民众产生重大公共卫生影响。识别与CVRF相关的风险特别高的亚组，有可能针对认知能力下降的预防或治疗。这项研究的创新之处在于寻找高龄男性退伍军人认知成功的预测因素，他们是损伤的高危人群，这可能导致识别保护性或预防性因素。

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.