Cardiac function as a mechanism for maladaptive brain aging

描述(申请人提供)：随着人口继续老龄化，痴呆症的发病率急剧增加，因此迫切需要确定大脑异常老化和痴呆症的危险因素。动物模型显示，心功能的改变会影响全身血流量，进而影响脑血流量的动态平衡。这种脑血流动态平衡的变化可能会带来加速年龄相关性脑损伤的风险。我们的初步研究表明，心脏功能与适应不良的大脑老化的标志有关。目前尚不清楚心脏功能是否加速了患有轻度认知障碍(MCI)的老年患者的神经成像或脑血管或阿尔茨海默病的认知标记物。MCI患者认知进展的风险更高，当存在伴随的血管疾病时，更容易出现更快的异常脑老化。我们提出的研究将检验心脏功能和不适应脑老化之间的关系，并为开发新的策略来延缓从MCI到痴呆的进展提供重要信息。使用前瞻性观察性配对设计，我们将横断面和纵向地将心脏功能与早期阿尔茨海默病的神经成像和认知标记物以及患有MCI的老年成年人和认知能力匹配的年龄、性别和种族匹配的正常成年人的脑血管变化联系起来。临床或亚临床心功能障碍可能是由于复杂的可预防或可治疗的系统机制，如炎症标志物和胰岛素抵抗的增强，或遗传因素，如载脂蛋白E，因此，我们将考虑系统和遗传因素作为心功能和脑老化之间潜在的中介机制。这项拟议的研究利用了由首席研究员指导的现有阿尔茨海默氏症协会资助的研究、NIA资助的波士顿大学阿尔茨海默氏症中心的参与者登记、最近侧重于招募和保留非裔美国人的美国复苏和再投资法案补充赠款，以及我们当地临床和翻译科学研究所提供的独特资源，该研究所拥有普通临床研究单位。

DESCRIPTION (provided by applicant): As the population continues to age, the incidence of dementia is dramatically increasing, resulting in an urgent need to identify risk factors for abnormal brain aging and dementia. Alterations in cardiac function influence systemic blood flow, which impacts cerebral blood flow homeostasis as demonstrated by animal models. Such changes in cerebral blood flow homeostasis may pose a risk for accelerating age-related brain injury. Our preliminary research suggests that cardiac function is related to markers of maladaptive brain aging. It is not yet clear if cardiac function accelerates neuroimaging or cognitive markers of cerebrovascular or Alzheimer's disease among aging individuals with mild cognitive impairment (MCI). Individuals with MCI are at increased risk for cognitive progression and susceptible to more rapid abnormal brain aging when concomitant vascular disease is present. Our proposed study will examine relations between cardiac function and maladaptive brain aging and provide important information for developing novel strategies to delay the progression from MCI to dementia. Using a prospective observational matched design, we will cross-sectionally and longitudinally relate cardiac function to neuroimaging and cognitive markers of early Alzheimer's disease and cerebrovascular changes among aging adults with MCI and age-, sex-, and race-matched cognitively normal adults. Clinical or subclinical cardiac dysfunction may be due to complex systemic mechanisms that are preventable or treatable, such as enhanced inflammatory markers and insulin resistance, or genetic factors, such as apolipoprotein E. Therefore, we will consider systemic and genetic factors as potential mediating mechanisms in relations between cardiac function and brain aging. The proposed study leverages an existing Alzheimer's Association funded study directed by the principal investigator, the participant registry of our NIA-funded Boston University Alzheimer's Disease Center, a recent American Recovery & Reinvestment Act supplement grant focused on African American recruitment and retention, and the unique resources afforded by our local Clinical and Translational Science Institute housing the General Clinical Research Unit.